Safer nicotine wiki - User contributions [en-gb]

Nicotine - People Living With Disabilities

2026-05-05T15:51:26Z

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[[File:Nicotine People Living With Disabilities.png|center]]
 

='''SMOKING INITIATION'''=

===2026: [https://www.sciencedirect.com/science/article/pii/S0306460325003570 Functional disability and the risk of subsequent smoking initiation: A prospective cohort analysis]===
*Functional disability was independently associated with a higher risk of smoking initiation.
*Adults with two or more functional impairments had almost twice the risk of smoking initiation compared with those without any impairments.
**Citation: Adebisi, Y. A., & Alshahrani, N. Z. (2026). Functional disability and the risk of subsequent smoking initiation: A prospective cohort analysis. Addictive Behaviors, 175, 108588. https://doi.org/10.1016/j.addbeh.2025.108588
*** Acknowledgments: This research was conducted independently without funding from any specific grant or organization. The open access publication fee was covered by the University of Glasgow through their agreement with Elsevier. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

='''SMOKING PREVALENCE and DISPARITIES'''=

='''SMOKING CESSATION'''=

===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]
**Citation: Polosa R, Rodu B, Caponnetto P, Maglia M, Raciti C. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduct J. 2013 Oct 4;10:19. doi: 10.1186/1477-7517-10-19. PMID: 24090432; PMCID: PMC3850892.
***Acknowledgments: R.P. is Professor of Medicine and he is supported by the University of Catania, Italy. He has received lecture fees and research funding from GlaxoSmithKline and Pfizer, manufacturers of stop smoking mediactions. He has also served as a consultant for Pfizer and Arbi Group Srl (Milano, Italy), the distributor of Categoria™ e-Cigarettes. R.P.’s research on electronic cigarettes is currently supported by LIAF (Lega Italiana AntiFumo). B.R.’s research is supported by unrestricted grants from tobacco manufacturers to the University of Louisville, and by the Kentucky Research Challenge Trust Fund. P.C. and C.R. are Assistant Professors and they are supported by the University of Catania, Italy. M.M is researcher and she is supported by the University of Catania, Italy. They have no relevant conflict of interest to declare in relation to this work.

='''STIGMA'''=

===2019: [https://www.jto.org/article/S1556-0864(19)30813-5/fulltext ES13.05 Stigma and Impact of Tobacco Control Policy]===
*The stigma reduces the funding available for lung cancer research. In the US, federal funding for lung cancer research per lung cancer death is only 15% of the funding amount for breast cancer per breast cancer death.
*In a Global Lung Cancer Coalition survey, one in five people (21%) agreed with the statement that they have less sympathy for people with lung cancer than for people with other types of cancer.
*Stigmatization of smokers has the greatest impact on the socioeconomically deprived, the disadvantaged populations. These populations have the highest prevalence of smokers and encounter the stigma of their race or disadvantage (poverty, disability, sexual preference, behavioral health etc.) in addition to the stigma associated with smoking.
*This stigmatization leads people who smoke to be less likely to seek medical care when they have symptoms, more likely to lie about their smoking, more likely to be refused access to care including curative surgery for early stage lung cancer unless they quit smoking, less likely to be offered smoking cessation help if they are uncomfortable disclosing their smoking status due to stigma and bias from their healthcare professional.
**Citation: Borondy Kitts, A. (2019). ES13.05 stigma and impact of tobacco control policy [Conference abstract]. Journal of Thoracic Oncology, 14(10 Suppl.), S48–S49. https://doi.org/10.1016/j.jtho.2019.08.130

='''THERAPEUTIC BENEFITS'''=

===Please see this page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine%20therapeutic%20benefits Nicotine therapeutic benefits]===

Nicotine - People Living With Disabilities

2026-05-05T15:49:39Z

Skip: created page

[[File:Nicotine People Living With Disabilities.png|center]]
 

=SMOKING INITIATION=

===2026: [https://www.sciencedirect.com/science/article/pii/S0306460325003570 Functional disability and the risk of subsequent smoking initiation: A prospective cohort analysis]===
*Functional disability was independently associated with a higher risk of smoking initiation.
*Adults with two or more functional impairments had almost twice the risk of smoking initiation compared with those without any impairments.
**Citation: Adebisi, Y. A., & Alshahrani, N. Z. (2026). Functional disability and the risk of subsequent smoking initiation: A prospective cohort analysis. Addictive Behaviors, 175, 108588. https://doi.org/10.1016/j.addbeh.2025.108588
*** Acknowledgments: This research was conducted independently without funding from any specific grant or organization. The open access publication fee was covered by the University of Glasgow through their agreement with Elsevier. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

=SMOKING PREVALENCE and DISPARITIES=

=SMOKING CESSATION=

===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]
**Citation: Polosa R, Rodu B, Caponnetto P, Maglia M, Raciti C. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduct J. 2013 Oct 4;10:19. doi: 10.1186/1477-7517-10-19. PMID: 24090432; PMCID: PMC3850892.
***Acknowledgments: R.P. is Professor of Medicine and he is supported by the University of Catania, Italy. He has received lecture fees and research funding from GlaxoSmithKline and Pfizer, manufacturers of stop smoking mediactions. He has also served as a consultant for Pfizer and Arbi Group Srl (Milano, Italy), the distributor of Categoria™ e-Cigarettes. R.P.’s research on electronic cigarettes is currently supported by LIAF (Lega Italiana AntiFumo). B.R.’s research is supported by unrestricted grants from tobacco manufacturers to the University of Louisville, and by the Kentucky Research Challenge Trust Fund. P.C. and C.R. are Assistant Professors and they are supported by the University of Catania, Italy. M.M is researcher and she is supported by the University of Catania, Italy. They have no relevant conflict of interest to declare in relation to this work.

=STIGMA=

===2019: [https://www.jto.org/article/S1556-0864(19)30813-5/fulltext ES13.05 Stigma and Impact of Tobacco Control Policy]===
*The stigma reduces the funding available for lung cancer research. In the US, federal funding for lung cancer research per lung cancer death is only 15% of the funding amount for breast cancer per breast cancer death.
*In a Global Lung Cancer Coalition survey, one in five people (21%) agreed with the statement that they have less sympathy for people with lung cancer than for people with other types of cancer.
*Stigmatization of smokers has the greatest impact on the socioeconomically deprived, the disadvantaged populations. These populations have the highest prevalence of smokers and encounter the stigma of their race or disadvantage (poverty, disability, sexual preference, behavioral health etc.) in addition to the stigma associated with smoking.
*This stigmatization leads people who smoke to be less likely to seek medical care when they have symptoms, more likely to lie about their smoking, more likely to be refused access to care including curative surgery for early stage lung cancer unless they quit smoking, less likely to be offered smoking cessation help if they are uncomfortable disclosing their smoking status due to stigma and bias from their healthcare professional.
**Citation: Borondy Kitts, A. (2019). ES13.05 stigma and impact of tobacco control policy [Conference abstract]. Journal of Thoracic Oncology, 14(10 Suppl.), S48–S49. https://doi.org/10.1016/j.jtho.2019.08.130

=THERAPEUTIC BENEFITS=

===Please see this page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine%20therapeutic%20benefits Nicotine therapeutic benefits]===

File:Nicotine People Living With Disabilities.png

2026-05-05T15:46:48Z

Skip:

Nicotine - Retracted Studies, Papers, and Articles

2026-04-26T11:18:32Z

Skip: /* Retractions by Author Request */

[[File:Corrections.png|center|]]
 

<big>'''On this page, we'll explore how mistakes in published works can happen, log commentaries on some published works, and list some examples of retracted papers.'''</big>

=How Mistakes Can Happen=

==Journals==

===2024: (Preprint) [https://www.preprints.org/manuscript/202410.2456/v2 Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy]===
*"This review explores methodological considerations for maximizing the precision and accuracy of observational cohort studies assessing the risk profiles of tobacco and nicotine products. These considerations, informed by the ROBINS framework for minimizing statistical bias, are anchored in a comprehensive characterization of exposure to all tobacco products currently or formerly used, with corroboration of dose-response relationships."
**Citation: Cohen, G., & Cook, S. (2024). Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy. Preprints. https://doi.org/10.20944/preprints202410.2456.v2

===2024: [https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1433626/full Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols]===
*"Updating and improving testing standards to incorporate basic conditions of experimental quality is necessary to achieve a more objective evaluation of the risk profile of ECs, which will provide valuable information to all stakeholders (consumers, health professionals, regulators, and the industries themselves)."
**Citation: Sussman RA, Sipala FM, Ronsisvalle S and Soulet S (2024) Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols. Front. Chem. 12:1433626. doi: 10.3389/fchem.2024.1433626

===2022: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis]===
*"Studies based on cross-sectional data with no information on age of e-cigarette initiation and age of diagnosis invariably overestimate associations by including cases that were diagnosed before e-cigarette exposure. Although the authors of those studies did not make causal claims in the reports, university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."
**Citation: Rodu B, Plurphanswat N. Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Intern Emerg Med. 2023 Jan;18(1):319-323. doi: 10.1007/s11739-022-03141-3. Epub 2022 Nov 25. PMID: 36434423.
*Commentary: [https://reason.com/wp-content/uploads/2022/12/Polosa-Commentary-IAEM-2022.pdf A tale of flawed e‑cigarette research undetected by defective peer review process]
*Article: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Diseases That Studies Linked to E-Cigarettes Generally Were Diagnosed Before Subjects Began Vaping]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018638/ Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research]===
*Conclusion: "Our critical appraisal reveals common, preventable flaws, the identification of which may provide guidance to researchers, reviewers, scientific editor, journalists, and policy makers. One striking result of the review is that a large portion of the high-ranking papers came out of US-dominated research institutions whose funders are unsupportive of a tobacco harm reduction agenda..."
**Citation: Hajat C, Stein E, Selya A, Polosa R; CoEHAR study group. Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research. Intern Emerg Med. 2022 Apr;17(3):887-909. doi: 10.1007/s11739-022-02967-1. Epub 2022 Mar 24. Erratum in: Intern Emerg Med. 2022 Aug;17(5):1561. PMID: 35325394; PMCID: PMC9018638.
*Article: [https://filtermag.org/vaping-research-quality/ Researchers Expose the Pitiful Quality of Highly Cited Vaping Studies]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506048/ A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol]===
*Abstract: "The inhalation of metallic compounds in e-cigarette (EC) aerosol emissions presents legitimate concerns of potential harms for users. We provide a critical review of laboratory studies published after 2017 on metal contents in EC aerosol, focusing on the consistency between their experimental design, real life device usage and appropriate evaluation of exposure risks. All experiments reporting levels above toxicological markers for some metals (e.g., nickel, lead, copper, manganese) exhibited the following experimental flaws: (i) high powered sub-ohm tank devices tested by means of puffing protocols whose airflows and puff volumes are conceived and appropriate for low powered devices; this testing necessarily involves overheating conditions that favor the production of toxicants and generate aerosols that are likely repellent to human users; (ii) miscalculation of exposure levels from experimental outcomes; (iii) pods and tank devices acquired months and years before the experiments, so that corrosion effects cannot be ruled out; (iv) failure to disclose important information on the characteristics of pods and tank devices, on the experimental methodology and on the resulting outcomes, thus hindering the interpretation of results and the possibility of replication"
**Citation: Soulet S, Sussman RA. A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol. Toxics. 2022 Aug 29;10(9):510. doi: 10.3390/toxics10090510. PMID: 36136475; PMCID: PMC9506048.

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787926/ Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===
*Abstract: "We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and “dry puffs”. The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design."
**Citation: Soulet S, Sussman RA. Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions. Toxics. 2022 Nov 22;10(12):714. doi: 10.3390/toxics10120714. PMID: 36548547; PMCID: PMC9787926.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769337/ Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations]===
*Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context.
**Citation: Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. PMID: 29375395; PMCID: PMC5769337.

===2017: [https://pubmed.ncbi.nlm.nih.gov/28864295/ E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions]===
*The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
**Citation: Farsalinos KE, Voudris V, Spyrou A, Poulas K. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions. Food Chem Toxicol. 2017 Nov;109(Pt 1):90-94. doi: 10.1016/j.fct.2017.08.044. Epub 2017 Aug 31. PMID: 28864295.

===2015: [https://pubmed.ncbi.nlm.nih.gov/25996087/ E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions]===
*Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid.
**Citation: Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. PMID: 25996087.

==Articles/Blogs==

===2024: [https://www.thefirebreak.org/p/formaldehyde-in-vapes-exposing-another Formaldehyde In Vapes? Exposing Another Chemical Scare]===
*"The same can be said of smokers who are discouraged from switching to vapes. In the name of reducing formaldehyde exposure that is already vanishingly small, the anti-vaping warriors have effectively urged people to continue using tobacco products that contain vastly higher quantities of the compound and kill some six million users annually. They manipulate public policy and deprive people–in this case smokers looking to quit–of products that could preserve their health and even save their lives."

===2024: [https://rodutobaccotruth.blogspot.com/2024/04/are-vape-aerosols-really-toxic.html Are Vape Aerosols Really Toxic?]===
*Addresses several studies

=Science Hygiene, the efforts to correct mistakes or seek retractions by experts=
*'''Notes:'''
**'''Dates denote when comments were published, not the paper's publication date.'''
**'''Clicking the link following "Comments RE" takes you to the comment. The article the comment is addressing will be linked under "Referring to."'''

==Addiction / Dependence / Use==
*To learn more about addiction/dependence, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine_-_Addiction/Dependence Nicotine - Addiction/Dependence]

===2024: Comments RE: [https://pubpeer.com/publications/40A35E1B6BCE23874F886C76971576 E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective]===
*Waa’s “Indigenous perspective” on e‐cigarette policies claiming Māori (the Indigenous people of New Zealand) were being exploited [1] omits some important context... (Lists examples)... Finally, Māori people have diverse views on vaping. For example, the Manager of the National Tobacco Control Advocacy Service, Hapai Te Hauora said in 2019, “Do you know who has a vested interest in vaping? Anyone who is sick of losing 5,000 whānau [family] members a year to tobacco; anyone who acknowledges the growing body of research showing vaping is helping many to break free of their tobacco addiction; anyone who cares about our people”. (Mendelsohn, Glover)
**Referring to: Waa A. E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective. Addiction. 2024 May 24. Epub ahead of print. PMID: 38794822. [https://onlinelibrary.wiley.com/doi/10.1111/add.16573 doi: 10.1111/add.16573].
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16462 E-cigarettes: A framework for comparative history and policy]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16660 Evidence and policy is certainly more complex than it seems]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16597 A tobacco control policy analysis framework that extends into the future]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16577 Adopting the Berridge et al.: Framework to understand differences in the e-cigarette policy between the Nordic countries]

===2024: Comments RE: [https://pubpeer.com/publications/E128EE4F19CD39411FAFDDB6A88FED Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity]===
*Despite the authors correcting recognizing that “no trends… should be inferred” between 2020 and 2021, they infer trends between 2021 and 2022, thus making the very same error, as the artifact relates to NYTS 2021 alone, not 2021 and every year thereafter. (Selya)
**Referring to: Mattingly DT, Hart JL. Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity. JAMA Netw Open. 2024;7(2):e2354872. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814427 doi:10.1001/jamanetworkopen.2023.54872]

===2024: Comments RE: [https://pubpeer.com/publications/DEF986999C6287FCD8FD4048A0B8EE Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022]===
*"Overall, Zhang et al. improperly conclude that there is a true uptick in dual- and poly-use of nicotine and tobacco in NYTS, but did not attribute any of their findings to a well-documented methodological artifact in NYTS 2021 which renders the findings inconclusive, as (in the words of official NYTS publications) 'differences between estimates might be due to changes in methodology, actual behavior, or both.' ” (Selya)
**Referring To: Zhang, B., Bannon, O., Chen, D. T., & Filippidis, F. T. (2024). Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022. Addictive Behaviors, 152, 107970. [https://www.sciencedirect.com/science/article/pii/S0306460324000194 https://doi.org/10.1016/j.addbeh.2024.107970]

===2023: Comments RE: [https://pubpeer.com/publications/3BF65B1CBECA15D0EC1068CF8628BC#2 Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth]===
*"Readers may be interested to know that there is now a comment to the Pierce et al paper from Shiffman and Hannon. The commenters raise questions about the conclusions drawn by the original authors and report alternative analyses of the same dataset." (Gitchell)
*"To this last point, Pierce and Strong’s response now reports a relevant analysis, and it directly contradicts their assertion in the original paper: they demonstrate that dependence among JUUL users in each age cohort was not different from dependence in users of other ENDS brands (though the trend is evidently for lower dependence among JUUL users)." (Shiffman)
**Referring To: Pierce JP, Leas EC, Strong DR. Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth. Pediatrics. 2023 Apr 1;151(4):e2022059158. PMID: 36942497. doi: https://doi.org/10.1542/peds.2022-059158

===2022: Comments RE: [https://pubpeer.com/publications/1FF8B75DFC81492DEBC8E214F63098 Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study]===
*A re-analysis of the data by Foxon & Shiffman (2) revealed that those analyses did not include replicate weights as specified in guidance from the PATH study team. Foxon & Shiffman (2) show that when the above analyses are performed with the replicate weights included, the associations above are statistically non-significant. (Foxon, Shiffman)
*(2) [https://www.mdpi.com/1660-4601/20/18/6715 Full Comment]
**Referring to: Wang Y, Duan Z, Weaver SR, Popova L, Spears CA, Ashley DL, Pechacek TF, Eriksen MP, Huang J. Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study. International Journal of Environmental Research and Public Health. 2022; 19(17):10837. [https://doi.org/10.3390/ijerph191710837 https://doi.org/10.3390/ijerph191710837]

===2021: Comments RE: [https://pubpeer.com/publications/57A74561DC4B1B43B91E18A95A24A5 Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users]===
*In summary, by imputing respondents who reported that they “don’t know” which ENDS brand they used to the non-JUUL group even if they may have used JUUL, and by relying on ‘any’ JUUL use definitions which defined as JUUL users those who “usually” used a different ENDS brand, the original analysis systematically biases against the focal brand (JUUL) being studied. (Foxon, Shiffman)
*In summary, the results of Mantey et al. are invalid, because they were based on a definition of JUUL use that is not justified by the brand information in the 2020 National Youth Tobacco Survey.(Rodu)
**Referring to: Mantey DS, Case KR, Omega-Njemnobi O, Springer AE, Kelder SH. Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users. Drug Alcohol Depend. 2021 Nov 1;228:109078. Epub 2021 Sep 24. PMID: 34614433; PMCID: PMC8595823. [https://doi.org/10.1016/j.drugalcdep.2021.109078 https://doi.org/10.1016/j.drugalcdep.2021.109078]

===2019: Comments RE: [https://pubpeer.com/publications/1F7BA5A2DEC4EF71CA4E7F34C69806 Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys]===
*These (improbable) increases conflict with official data from Statistics Canada that were released shortly after the publication of the paper drawn from the Canadian Community Health Survey, with a representative sample of 65,000. (Bates)
*The Counterfactual: [https://clivebates.com/canada-takes-a-wrong-turn-after-a-flawed-paper-induces-moral-panic-about-youth-vaping-and-smoking/ Canada takes a wrong turn after a flawed paper induces moral panic about youth vaping and smoking]
**Referring to: Hammond D, Reid JL, Rynard VL, Fong GT, Cummings KM, McNeill A, Hitchman S, Thrasher JF, Goniewicz ML, Bansal-Travers M, O'Connor R, Levy D, Borland R, White CM. Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys. BMJ. 2019 Jun 20;365:l2219. Erratum in: BMJ. 2020 Jul 10;370:m2579. PMID: 31221636; PMCID: PMC6582265. [https://doi.org/10.1136/bmj.l2219 doi: 10.1136/bmj.l2219]
**[https://www.bmj.com/content/370/bmj.m2579 Corrections]: "The authors of this paper (BMJ 2019;365:l2219, doi:10.1136/bmj.l2219, published 20 June 2019) have provided an update on estimates of smoking among adolescents and vaping from the ITC Youth and Vaping Surveys conducted in Canada, England, and the United States (see supplementary file for details).
**I note with interest that another paper in BMJ includes the same red-box Correction. However with this one, upon clicking, it opens a page displaying a direct and complete explanation of the correction and a pledge that the paper itself will be updated (it has been). It would be welcome if the journal would apply the same level of rigor to the Hammond et al paper (Gitchell).

===2018: Comments RE: [https://pubpeer.com/publications/58B4D5D27C6A7C45EE3A094D324368 Prevalence and correlates of JUUL use among a national sample of youth and young adults]===
*The results from this article are uninformative, because the authors did not include simple crosstabs of the raw numbers showing the overlap in current use of ENDS, JUUL and combustible products. They failed to denote current ENDS use in the model for Table two. (Rodu)
**Referring to: Vallone DM, Bennett M, Xiao H, Pitzer L, Hair EC. Prevalence and correlates of JUUL use among a national sample of youth and young adults. Tob Control. 2019 Nov;28(6):603-609. Epub 2018 Oct 29. PMID: 30377241. [https://doi.org/10.1136/tobaccocontrol-2018-054693 https://doi.org/10.1136/tobaccocontrol-2018-054693]

===2014: Comments RE: [https://sci-hub.wf/10.1001/jamapediatrics.2014.733 Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents]===
*"In a cross-sectional study, the observed relationship between e-cigarette use and higher and more sustained levels of smoking does not imply causation. Moreover, such studies do not take into account other population characteristics, which may play a crucial role when determining potential causation.2,3 Although the authors acknowledged this limitation in the text, they ended up drawing a conclusion that misleads the public into thinking e-cigarettes are leading to smoking initiation and addiction among adolescents." (Farsalinos, Polosa)
*"Although Dutra and Glantz highlighted an important trend in e-cigarette use among our nation’s youth, failing to consider e-cigarette use in the context of other tobacco products may place undue emphasis on e-cigarettes, overshadowing the importance of the current use of multiple tobacco products as well as experimentation with cigars, smokeless tobacco, and hookah in this population." (Delnevo, Bover Manderski,Giovino)
**Referring to: Dutra LM, Glantz SA. Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. JAMA Pediatr. 2014;168(7):610–617. [https://jamanetwork.com/journals/jamapediatrics/fullarticle/1840772 doi:10.1001/jamapediatrics.2013.5488]

==Cancer==

===2024: Comments RE: [https://pubpeer.com/publications/AC3CFEABA70EC0D0AEBD1568368478 Vaping, Smoking and Lung Cancer Risk]===
*There are 10 issues with this study - Reverse Causality, Combining of Current & Ex-Smokers, Temporal Confounding, Contradiction with National Lung Cancer Trends, Absence of a Dose-Response Relationship, Unclear Definition and Consistency of Use Measures, Recall and Reporting Bias, Biological Implausibility, Uniform Effect Across Histologic Cell Types, Age at smoking initiation not adjusted for. [see commentary for further details] (Herzig)
**Referring to: Bittoni MA, Carbone DP, Harris RE (2024) Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther 9: 10229. https://doi.org/10.29011/2574-710X.10229.

==Cardiovascular==

===2024: Comments RE: [https://pubpeer.com/publications/CD0E2CD6E82EB2F69173F5A1193331#1 Electronic Cigarette Use and Myocardial Infarction]===
*"The research question posed is an important one, since the number of people who have never smoked and who report using e-cigarettes appears to have increased in recent years. However, we are concerned that the methods used in the Alzahrani study [1] make the reported findings highly suspect and the conclusion reached unlikely. This includes: 1) temporality concerns; 2) measurement, diagnosis, and biological plausibility concerns; 3) sample size concerns; 4) model design concerns; and 5) uncareful language." (Foxon, Polosa, Niaura, Cummings, Siegel, Benowitz)
**[https://twitter.com/FloeFoxon/status/1748004148987965469 Tweetorial]
*See also: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055619/ Questionable Effects of Electronic Cigarette Use on Cardiovascular Diseases From the National Health Interview Survey (NHIS, 2014-2021)]
**The study by Alzahrani made erroneous claims and overstated the association between e-cigarettes and myocardial infarction. Our replication shows that the association is driven by age and there were no statistically significant associations with other cardiovascular diseases, coronary heart diseases, and stroke.
***Referring to: Alzahrani T (November 06, 2023) Electronic Cigarette Use and Myocardial Infarction. Cureus 15(11): e48402. [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction doi:10.7759/cureus.48402]

===2022: Comments RE: [https://pubpeer.com/publications/B1574611ED725601C17C3766DB164E Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular disease. A recent analysis by my research group of data from the Population Assessment of Tobacco and Health, which contains this essential temporal information, provides definitive evidence that the results from Osei et al. are deficient and unreliable." (Rodu)
**Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Benjamin EJ, Hall ME, DeFilippis AP, Stokes A, Bhatnagar A, Nasir K, Blaha MJ. Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers. Am J Med. 2019 Aug;132(8):949-954.e2. doi: [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction#!/ 10.1016/j.amjmed.2019.02.016]. Epub 2019 Mar 8. PMID: 30853474.

===2022: Comments RE: [https://pubpeer.com/publications/D075EB2EED18CA0311BAC77C783777 Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use]===
*"The study by Vindhyal et al. used the National Health Interview Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
**Referring to: Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS. Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use. Cureus. 2020 Aug 8;12(8):e9618. [https://pubmed.ncbi.nlm.nih.gov/32923219/ doi: 10.7759/cureus.9618]. PMID: 32923219; PMCID: PMC7478662.

===2020: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-smoking-vaping-and-stroke-risk/ Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults]===
*“These findings arise from subgroup analysis involving multiple hypothesis tests and are therefore unreliable. Contrary to the authors’ claim, this study provides no evidence that vaping increases the risk of stroke accrued from smoking tobacco.” (Britton)
*“While the paper itself is careful in interpreting the finding, the press release is grossly misleading. The study provides no justification for the claim that vaping increases the risk of stroke.” (Hajek)
*"While this paper highlights the need to continue studying the potential health effects of e-cigarette use, the results should be interpreted with caution as the observed associations may be simply due to unmeasured confounding and reverse causality.” (Shahab)
**Referring to: Parekh T, Pemmasani S, Desai R. Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults. Am J Prev Med. 2020 Mar;58(3):446-452. [https://pubmed.ncbi.nlm.nih.gov/31924460/ doi: 10.1016/j.amepre.2019.10.008]. Epub 2020 Jan 7. PMID: 31924460.

===2020-2022: Comments RE: [https://pubpeer.com/publications/E4180AE40B2A0F076D7D07CE0B7961 Association Between Electronic Cigarette Use and Myocardial Infarction]===
*Multiple comments:
**"The study by Alzahrani et al. used data from the National Health Interview Survey, which contains no information about when participants started to smoke or vape, and when they were diagnosed with a myocardial infarction." (Rodu)
**"E-cigarettes first appeared in the US at about 2009 and their use picked up from about 2013. In the cohorts from 2014 and 2016 that this study used, most participants with a history of MI can be expected to have had their MI before they tried e-cigarettes...The authors’ conclusions are thus misleading on an important public health issue. The article has been used e.g. to claim that vaping increases risk of cardiovascular disease by the WHO Director Ghebreyesus (DOI: 10.1016/S0140-6736(19)31730-1). The data that the paper reports show no such thing." (Hajek)
*See also: [https://www.ajpmonline.org/article/S0749-3797(21)00290-7/fulltext 2021]
**"Alzahrani and colleagues rightly point out that their models test for and thus demonstrate statistically independent effects of smoking and vaping, but if vaping and smoking are not actually independent contributors to identifying MI occurrence—that is, if the association between e-cigarette use and MI occurrence varies as a function of combustible cigarette use—then the main-effects model cannot be used to draw conclusions about the association between e-cigarette use and MI, independent of (or regardless of) one's history of combustible cigarette use." (Critcher, Siegel)
*See also: [https://sci-hub.wf/10.1016/j.amepre.2019.03.012 2019]
**"As the debate on the risks−benefits of electronic-cigarettes continues, a rigorous evidence base is critical. Although determining whether the use of e-cigarettes carries excess risk for future MI is important, it is not possible through the analysis of cross-sectional data, such as the National Health Interview Survey data, from which temporality cannot be inferred. Equally important, we were unable to replicate the authors’ findings. Given the importance of this topic to public health, we request that the authors provide a full and comprehensive explanation for the discrepancies noted and temper their conclusions about “increased risk of myocardial infarction” to reflect the limitations of cross-sectional data." (Bover Manderski, Singh, Delnevo)
* See also: [https://sci-hub.wf/10.1016/j.amepre.2018.06.007 2018]
**"Of concern,however, is the fact that 95% of EC users were also former or current tobacco cigarette (TC) smokers, and the timing of the MI relative to onset of EC use is unknown. (Middlekauff, Gornbein)
*See also: [https://sci-hub.se/10.1016/j.amepre.2018.11.013 2018]
**"Our findings show the well-established limitations of cross-sectional studies, which cannot justify any claims about causal inference, as mentioned in the conclusion by Alzahrani and colleagues.1 Therefore, the conclusion of their study is incorrect and should be revised." (Farsalinos, Niaura)
***Referring to: Alzahrani T, Pena I, Temesgen N, Glantz SA. [http://Association%20Between%20Electronic%20Cigarette%20Use%20and%20Myocardial%20Infarction Association Between Electronic Cigarette Use and Myocardial Infarction]. Am J Prev Med. 2018 Oct;55(4):455-461. doi: 10.1016/j.amepre.2018.05.004. Epub 2018 Aug 22. Erratum in: Am J Prev Med. 2019 Oct;57(4):579-584. PMID: 30166079; PMCID: PMC6208321.

==Cessation==
To learn more about smoking cessation, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]

===2024: Comments RE: [https://www.linkedin.com/posts/jeffrey-l-weiss_publichealth-mondaythoughts-thoughtleadership-activity-7231288859165143042-XOSF?utm_source=combined_share_message&utm_medium=member_desktop Adult Smoking Cessation — United States, 2022]===
*"Concealing important information is not meaningfully different from disseminating falsehoods. Smokers who have been unable or unwilling to quit all use of nicotine with traditional smoking cessation medicines deserve to know that they still have alternatives. It should be unacceptable that the “lead federal agency for comprehensive tobacco prevention and control” would keep potentially life-saving information from them." (Weiss)
***Referring to: VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641. DOI: http://dx.doi.org/10.15585/mmwr.mm7329a1

===2024: Comments RE: [https://pubpeer.com/publications/A21E464F1BA2A64B02D7ABF3A88965 Declines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surge]===
*"However, the authors’ conclusions are based on questionable methodological decisions and flawed analyses. Most notably:
**A. The joinpoint analysis of declining cigarette smoking is incorrectly conducted, in a way that obscures more rapid declines in current cigarette smoking after 2002;
**B. Rather than conducting a standard analysis (i.e., a weighted and adjusted analysis of e-cigarette use and smoking trends), authors instead base their conclusions on tallying states that meet certain ad hoc and stringent criteria for (unadjusted) e-cigarette use and smoking trends; and
**C. Analyses focus on an inappropriately narrow time window that does not fully capture the relevant dynamics. Together these flaws substantially underestimate the degree to which e-cigarettes may have displaced or offset cigarette smoking among youth and young adults.
**Moreover, the conclusion that e-cigarette uptake is independent of the declines in cigarette smoking runs counter to a large and varied body of evidence that e-cigarettes substitute for or displace cigarettes. The authors only discuss two such papers, attempting to undermine their conclusions using some of the same flaws that underlie their own analyses, and neglect to mention the larger body of evidence. Together, this yields an article that could cause readers to hold a distorted view of the available evidence on these important issues." (Selya, Gitchell, Foxon, Sembower, Niaura)
***Referring to: Pierce JP, Luo M, McMenamin SB, et alDeclines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surgeTobacco Control Published Online First: 08 November 2023. [https://tobaccocontrol.bmj.com/content/early/2023/11/08/tc-2022-057907 doi: 10.1136/tc-2022-057907]

===2016-2020: Comments RE: [https://pubpeer.com/publications/E2628F04937D0DBD870E115CB41C8B E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis]===
*Multiple Comments, many linking to more information
**"The most obvious issue is that the result is based on studies that have no bearing on whether e-cigarettes are effective or not. This is because vapers who successfully quit smoking were excluded and only those who failed to do so were retained. The studies were not at fault, they were just not set up to evaluate quit rates in smokers who try and not try vaping. The fault is with misinterpreting their results. The letter in LRM referenced above provides more details." (Hajek)
*[https://www.sciencemediacentre.org/expert-reaction-to-meta-analysis-looking-at-e-cigarette-use-and-smoking-cessation/ Expert Reaction]
**“Publication of this study represents a major failure of the peer review system in this journal.” (West)
**"The current paper represents the latest attempt to bring together the existing literature on e-cigarettes for smoking cessation. While its breadth is to be commended, its conclusions (that e-cigarettes don’t work for smoking cessation) are at best tentative and at worst incorrect. The main reason for this is that attempting to directly compare the results of a body of literature that uses such a wide range of study designs and includes such variable (and often poorly defined) populations and outcomes is difficult, if not impossible. Some of the observational studies included in the review, in particular, suffer from a range of limitations that don’t allow us to reliably assess whether e-cigarettes help smokers quit." (Bauld)
**“Evidence from practice in England shows that two out of three smokers who combined e-cigarettes with additional expert support from a local stop smoking service quit successfully and while dual use is a complex issue, many vapers report using an e-cigarette to cut down and ultimately quit." (O'Connor)
**“This review is grossly misleading in my opinion. There are several problems with the way studies were selected and used, but the main flaw is simple, though not easy to spot. The studies that are presented as showing that vaping does not help people quit only recruited people who were currently smoking and asked them if they used e-cigarettes in the past. This means that people who used e-cigarettes and stopped smoking were excluded. The same approach would show that proven stop-smoking medications do not help or even undermine quitting." (Hajek)
**“This review is not scientific. The information included about two studies that I co-authored is either inaccurate or misleading. In addition, the authors have not included all previous studies they could have done in their meta-analysis. I believe the findings should therefore be dismissed. I am concerned at the huge damage this publication may have – many more smokers may continue smoking and die if they take from this piece of work that all evidence suggests e-cigarettes do not help you quit smoking; that is not the case." (McNeill)
*[https://clivebates.com/who-will-be-duped-by-error-strewn-meta-analysis-of-e-cigarette-studies/ Who will be duped by error-strewn ‘meta-analysis’ of e-cigarette studies?]
**"There are multiple challenges with interpreting the e-cigarette studies routinely appearing in the scientific literature – and over-interpretation is all too easy or even deliberate." (Bates)
*[https://web.archive.org/web/20151026231500/http://truthinitiative.org/sites/default/files/2015.06.30%20E-Cig%20FDA%20Workshop%20Docket%20FINAL.pdf Legacy Foundation (now Truth Initiative) submission to the FDA]
**"While the majority of the studies we reviewed are marred by poor measurement of exposures and unmeasured confounders, many of them have been included in a meta-analysis that claims to show that smokers who use e-cigarettes are less likely to quit smoking compared to those who do not.[73] This meta- analysis simply lumps together the errors of inference from these correlations. As described in detail above, quantitatively synthesizing heterogeneous studies is scientifically inappropriate and the findings of such meta-analyses are therefore invalid."
**"Findings from the studies with the strongest methodologies suggest that e-cigarettes are effective in helping adult smokers to quit or to reduce their cigarette consumption and that rates of smoking cessation with e-cigarettes are similar to rates of cessation with nicotine replacement therapy."
*[https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(16)30024-8.pdf Correspondence]
**"There are other problems—such as selective inclusion of studies, and selective reporting of data from studies that were included —and limitations the authors acknowledge in the text but ignore in their conclusions. Detailed criticism of the methods is, however, not needed, because lumping incongruous studies together—which were mostly not designed to evaluate the efficacy of e-cigarettes, and contain no useful information on this topic unless misinterpreted—makes no scientific sense in the first place." (Hajek, McRobbie, Bullen)
*[https://antithrlies.com/2016/01/17/sunday-science-lesson-what-is-meta-analysis-and-why-was-glantzs-inherently-junk/ Sunday Science Lesson: What is “meta-analysis”? (and why was Glantz’s inherently junk?)]
**"Glantz’s meta-analysis is not just junk science because of details about the studies, though those are problems in themselves. It is junk science because there are probably not even two of the studies in his collection that are similar enough to average together, let alone all of them." (Phillips)
***Referring to: Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016 Feb;4(2):116-28. [https://pubmed.ncbi.nlm.nih.gov/26776875/ doi: 10.1016/S2213-2600(15)00521-4]. Epub 2016 Jan 14. PMID: 26776875; PMCID: PMC4752870.

==COVID==

===2022: Comments RE: [https://pubpeer.com/publications/362B01D2B4E5398302F22585990F19#1 Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review]===
*"It is important to state that there is no empiric evidence of transmission of the SARS-CoV-2 virus or any other pathogen through vaping expirations. None of the sources cited by the authors on this issue (references cited in the first paragraph above) provide such evidence, they merely speculate about it in very vague general terms.
*Given the lack of experimental detection, the potential plausibility and scope of this pathogen transmission should be discussed through well structured models based on the theory and data of pathogen transmission mechanisms. Unfortunately, the authors missed three extensive articles in which we undertook this task (links to the articles). (Sussman)
**Referring to: Singhal S, Degano C, Berenbaum E, Keller-Olaman S. Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review. [https://pubmed.ncbi.nlm.nih.gov/35881057/ J Can Dent Assoc. 2022 Jan;88:m1]. PMID: 35881057.

===2020: Comments RE: [https://pubpeer.com/publications/CEB008BBD48F89272321EB50092793 Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19]===
*Multiple Comments:
**"This article is getting severe criticism on Twitter. This thread summarises one issue and links to threads on other, more classic, problems." (Brown) Further comments by the same author (Brown) point out some errors in tables.
**"The authors surveyed and controlled for socioeconomic factors, ethnicity and compliance with confinement precautions, but not for other risk behaviors besides smoking or vaping (such as alcohol drinking, substance usage, unprotected sex). The lack of this important comparative context further weakens the conclusions of this study." (Sussman)
**"Flaws in the paper itself are only one part of the problem that needs to be addressed by the authors. The other is the public relations offensive mounted on the back of the paper once it was published in the Journal of Adolescent Health on August 11." "Unsurprisingly, such an incendiary claim generated considerable media coverage, even though there is no basis for it in fact or evidence." "Finally, there was a political dimension. On the same day as the article was published, August 11, 2020, Illinois Congressman Raja Krishnamoorthi, Chairman of the Subcommittee on Economic and Consumer Policy, found time to write a press release and letter to the Commissioner of the Food and Drug Administration, Dr. Stephen Hahn demanding FDA "clear the market of e-cigarettes" in response to the study." (Bates)
*See Also:[https://www.qeios.com/read/A58MQC Qeios 1]
**"In this brief peer review, we argue that the data reported by Gaiha et al (https://doi.org/10.1016/j.jadohealth.2020.07.002) regarding associations between vaping and COVID-19 testing are so suspect that any conclusions drawn from it cannot be relied upon. We discuss six main areas of concern and conclude that the paper should be retracted." (Gitchell, Kleykamp, Niaura, Shiffman, Cummings, Sweanor, Abrams)
*[https://www.qeios.com/read/TCEJ7G Qeios 2]
**"In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study." (Farsalinos, Niaura)
***Referring to: Gaiha SM, Cheng J, Halpern-Felsher B. Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19. J Adolesc Health. 2020 Oct;67(4):519-523. [https://www.jahonline.org/article/S1054-139X(20)30399-2/fulltext doi: 10.1016/j.jadohealth.2020.07.002]. Epub 2020 Aug 11. PMID: 32798097; PMCID: PMC7417895.

==Diabetes and Prediabetes==

===2022: Comments RE: [https://pubpeer.com/publications/D3C8E2035BE5C164E9BC19D8D50571 E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey]===
*"The results by Atuegwu et al. are deficient and unreliable, because the authors used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease." (Rodu)
**Referring to: Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM. E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey. Drug Alcohol Depend. 2019 Dec 1;205:107692. [https://pubmed.ncbi.nlm.nih.gov/31707269/ doi: 10.1016/j.drugalcdep.2019.107692]. Epub 2019 Oct 28. PMID: 31707269; PMCID: PMC6893144.

===2022: Comments RE: [https://pubpeer.com/publications/3638F392BE76DCA7CA57ABC8E554BF#1 The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018]===
*"The study by Zhang et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Their results are deficient and unreliable, because a recent analysis by my research group provides definitive evidence that the vast majority of diseases reported by vapers in cross-sectional surveys had been diagnosed before survey participants initiated the behavior." (Rodu)
*2022 Article: [https://www.acsh.org/news/2022/03/08/ignore-headlines-theres-no-science-linking-vaping-prediabetes-16172 Ignore The Headlines: There's No Science Linking Vaping To Prediabetes] (English)
**Limitations of this study include self-report of tobacco use and lack of medical confirmation of prediabetes and other diet information
**BRFSS is a cross-sectional survey, so a causal relationship between E-cigarette use and prediabetes cannot be inferred.
***Referring to: Zhang Z, Jiao Z, Blaha MJ, Osei A, Sidhaye V, Ramanathan M Jr, Biswal S. The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018. Am J Prev Med. 2022 Jun;62(6):872-877. [https://www.ajpmonline.org/article/S0749-3797(22)00024-1/fulltext doi: 10.1016/j.amepre.2021.12.009]. Epub 2022 Mar 3. PMID: 35597566.

==EVALI==

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
**Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Flavors==
*For more information about flavors, please see our page: [https://safernicotine.wiki/mediawiki/index.php/ENDS_Flavors ENDS Flavors]

===2022: [https://pubpeer.com/publications/62DEA1F7805686A6D0172A6B69EFFA Levels of menthol, nicotine and cooling agents measured in JUUL products purchased across a three-year period]===
*The implications made about JUUL products in this study are contradicted by our own contemporaneous and detailed product and manufacturing records and are more readily explained by a methodological artifact that the authors have not fully reported, even after a direct prompt before submitting the manuscript. (Gillman)
**[https://tobaccocontrol.bmj.com/content/33/2/e1 Correction to original paper]
*The PubPeer entry from Juul Labs Inc. (JLI) raises a number of serious questions about this research, the research conduct of the authors, and the editorial practices of the journal. (Bates)
*Referring To: Yassine A, El Hage R, El-Hellani A, et al. Levels of menthol, nicotine, and cooling agents measured in JUUL products purchased across a three-year period Tobacco Control 2022;31:s234-s237. [https://doi.org/10.1136/tc-2022-057506 https://doi.org/10.1136/tc-2022-057506]

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
*Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Gateway==
*To learn more about Gateway, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_are_a_gateway_to_smoking Myth: Alternative nicotine products are a gateway to smoking]

===2024: Comments RE: [https://pubpeer.com/publications/EAD2B506813B485178822E76F2377F Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey]===
*"Causation vs. association. While the authors are careful in most places to avoid claiming that this association is causal, the authors seem to ultimately conclude in favor of a (causal) gateway hypothesis, which is inappropriate given unmeasured confounding by other “common liability” factors, and the cross-sectional nature of the data." (Selya)
*Referring to: Li S, Zeng X, Di X, Liu S. Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey. Front Public Health. 2024 Jan 15;11:1272680. PMID: 38288432; PMCID: PMC10823011 [https://pubmed.ncbi.nlm.nih.gov/38288432/ doi: 10.3389/fpubh.2023.1272680]

===2022: Comments RE: [https://pubpeer.com/publications/9F3E9313EAE06ED991EE4834D69C8E Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study]===
*"The present re-analysis shows that the report of a gateway effect in the NYTS data by Harrell et al. is not supported by these data when appropriate statistical methodology is applied." (Foxon)
*Referring to: Harrell MB, Mantey DS, Chen B, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Prev Med. 2022 Nov;164:107265. Epub 2022 Sep 22. PMID: 36152819; PMCID: PMC10381788. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381788/ doi: 10.1016/j.ypmed.2022.107265]

===2021: Comments RE: [https://www-sciencemediacenter-de.translate.goog/alle-angebote/research-in-context/details/news/e-zigaretten-als-einstieg-zum-zigarettenrauchen/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en-US Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking]===
*Statements:
*; Prof. Dr. Ute Mons, Head of the Cardiovascular Epidemiology of Aging Working Group, Clinic III for Internal Medicine, Cologne University Hospital : “Since there was no statistical control for possible disruptive factors, a causal interpretation, as it is heard between the lines by the authors, is not justified. It should also be taken into account that the study period ran from 2013 to 2017, but the sale of e-cigarettes to young people in the USA was not banned until 2016.For a long time, e-cigarettes were simply more readily available to young people than conventional cigarettes."
*; Prof. Dr. Daniel Kotz, Professor of Addiction Research and Clinical Epidemiology, Institute for General Practice, University Hospital Düsseldorf : “Overall, there is no clear scientific evidence that e-cigarettes are an entry point into tobacco consumption for adolescents and young adults. It is more likely that a personal basic inclination towards nicotine products and the social environment influence the consumption of e-cigarettes or tobacco independently of one another (so-called common liability theory). International studies show that tobacco smoking is falling among adolescents, even in countries where the consumption of e-cigarettes has increased [2]. This contradicts the so-called gateway theory."
*;Prof. Dr. Heino Stöver, Managing Director of the Institute for Addiction Research Frankfurt (ISFF), Frankfurt University of Applied Sciences : “The study is not suitable for making valid statements about e-cigarettes. The main weak point of the study is that it does not take into account the motives for smoking. According to the current state of research, there is no significant causal relationship between the use of e-cigarettes and subsequent smoking. The research situation points in the opposite direction: The majority of adolescents use e-cigarettes no more than experimenting or occasionally using them. In the future, a research design is required that not only examines correlation but also real causality. Unfortunately, this is still not the case. Not even in this study. Such shortcomings underestimate the great and positive role of the e-cigarette in smoking cessation.With 95 percent fewer pollutants than conventional cigarettes, they are well suited for smokers who want to get rid of their addiction and minimize their risk."
*Refering to: John P. Pierce, Ruifeng Chen, Eric C. Leas, Martha M. White, Sheila Kealey, Matthew D. Stone, Tarik Benmarhnia, Dennis R. Trinidad, David R. Strong, Karen Messer; Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking. Pediatrics February 2021; 147 (2): e2020025122. [https://publications.aap.org/pediatrics/article/147/2/e2020025122/36274/Use-of-E-cigarettes-and-Other-Tobacco-Products-and?autologincheck=redirected 10.1542/peds.2020-025122]

===2018: Comments RE: [https://rodutobaccotruth.blogspot.com/2018/01/tobacco-gateway-report-omits-important.html Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015]===
*The Chaffee article emphasizes odds ratios but omits or obscures important contextual information. While teens who try one tobacco product are more likely to try another, the dominant gateway in the PATH survey was from no previous tobacco use to cigarettes. (Rodu)
*Referring to: Watkins SL, Glantz SA, Chaffee BW. Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015. JAMA Pediatr. 2018;172(2):181–187. [http://doi:10.1001/jamapediatrics.2017.4173 doi:10.1001/jamapediatrics.2017.4173]

===2016: Comments RE: [http://tobaccoanalysis.blogspot.com/2016/06/new-pediatrics-study-provides.html E-Cigarettes and Future Cigarette Use] (#1)===
*The study counted anyone who had even puffed a cigarette once as being a smoker. So theoretically, a subject could have had a single puff of an e-cigarette and hated it, and then had a single puff of a cigarette and hated it, and they would be considered someone who initiated smoking because of vaping first. (Siegel)
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-e-cigarettes-and-future-cigarette-use/ E-Cigarettes and Future Cigarette Use] (#2)===
*Prof. Ann McNeill, Professor of Tobacco Addiction at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London : “The gateway hypothesis in the addictions field is frequently used but is highly contested as it has a poor evidence base in general. This study does nothing to strengthen that evidence base.”
*Prof. Peter Hajek, Director of the Tobacco Dependence Research Unit at Queen Mary University of London : "Like several previous studies of this type, this one just shows that people who try things, try things."
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://tobaccoanalysis.blogspot.com/2016/08/new-study-purports-to-show-that-e-cigs.html E-cigarette use is differentially related to smoking onset among lower risk adolescents ]===
*"To be clear, the rest of the story is that this new study provides no evidence that e-cigarettes are a gateway to smoking. Instead, it confirms that actual drug-related risk-taking behavior is a much better predictor of other drug-related risk-taking behavior than simply asking a kid if he thinks he will try another drug in the future or asking a kid how rebellious he is or how much his parents support him."
*"This second problem is that smoking initiation was measured by any experimentation with cigarettes, even if just a puff. So many of the youth in the sample may have puffed on a single e-cigarette at baseline and then puffed on a single cigarette some time over the next year and that would be considered as providing evidence that e-cigarettes are a "gateway" to smoking." (Siegel)
*Referring to: Wills TA, Sargent JD, Gibbons FX, et al E-cigarette use is differentially related to smoking onset among lower risk adolescents [https://tobaccocontrol.bmj.com/content/26/5/534 Tobacco Control 2017;26:534-539].

===2026: Comments RE: Flavored Electronic Cigarette Use and Smoking Among Youth===
*"The problems are obvious to those with any experience in statistics; the paper suffers from recall bias, sampling bias, and drawing causal conclusions from a cross-sectional survey. One of those confounders would be troubling yet the paper contains all of them." ([https://www.acsh.org/news/2016/11/07/all-animals-arent-cows-all-tobacco-isnt-cigarettes-and-surveys-arent-science-10412 Campbell])
*"This is a great example of the widespread bias against e-cigarettes that has taken hold in the tobacco control movement. Instead of presenting the study as showing equivocal results, the investigators and the American Academy of Pediatrics have both "chosen sides." This is not science; it is biased interpretation and presentation of science." ([https://tobaccoanalysis.blogspot.com/2016/11/investigators-botch-interpretation-of.html Siegel])
*Referring to: Hongying Dai, Jianqiang Hao; Flavored Electronic Cigarette Use and Smoking Among Youth. Pediatrics December 2016; 138 (6): e20162513. 10.1542/peds.2016-2513

===2014: Comments RE: [https://tobaccoanalysis.blogspot.com/2014/08/politicians-lie-to-public-about.html Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study]===
*"In a press release issued Monday by 13 members of Congress, a group of politicians claimed that there is "more" evidence that electronic cigarettes are a gateway to smoking...The reference which supports this assertion is a study by Dutra and Glantz which purports to provide data showing that electronic cigarettes are aggravating the tobacco epidemic among youth...The authors of this study make one of the most cardinal errors in all of epidemiology. They ignore the principle that correlation does not equal causation." (Siegel)
*Referring to: Dutra LM, Glantz SA. Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study. JAMA Pediatr. 2014 Jul;168(7):610-7. [http://doi:%2010.1001/jamapediatrics.2013.5488 doi: 10.1001/jamapediatrics.2013.5488]. Erratum in: JAMA Pediatr. 2014 Jul;168(7):684. PMID: 24604023; PMCID: PMC4142115.

==HPHC - Harmful and Potentially Harmful Constituents==

===2024: Comments RE: [https://www.pubpeer.com/publications/2D5B14D827614B6D4EFC821DCD2715 In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting]===
*"As a summary: the study by Beard et al [1] was conducted under such unrealistic conditions that its results (including its cytotoxic analysis) have little relevance to consumers and regulators." (Soulet, Sussman)
*Referring to: Beard JM, Collom C, Liu JY, Obiako P, Strongin RM, Zavala J, Sayes CM. In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting. Toxicology. 2024 Jun 13;506:153865. doi: 10.1016/j.tox.2024.153865. Epub ahead of print. PMID: 38876198.

===2024: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-observational-study-of-lead-and-uranium-levels-in-urine-of-teen-vapers/ Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring]===
*"More important, to me as a statistician at least, is that this research can’t establish that the higher levels of lead and uranium in the urine of participants who said they vaped more often were actually caused by their vaping." (McConway)
*"No control group (i.e., adolescents without any e-cigarette use) was included in the analysis...This study therefore cannot tell us anything about absolute increase in exposure to heavy metals from e-cigarette use in this population, only about relative exposure among less and more frequent e-cigarette users." (Shahab)
*See Also: [https://pubpeer.com/publications/E1834A07BDF105C94CC44DD0815856 PubPeer] "The reported mean values are then consistently far below the limit of detection. To draw any conclusions from values below LOD, is bad practice at best."
*Referring to: Kochvar A, Hao G, Dai HD Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring Tobacco Control Published Online First: 29 April 2024. doi: 10.1136/tc-2023-058554

===2023: Comments RE: [https://pubpeer.com/publications/F7311DC3982D9CD03C060190C9CFCB Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study]===
*The article has several serious shortcomings
**REPRODUCIBILITY AND LACK OF CRUCIAL INFORMATION.
**INAPPROPRIATE AIRFLOW FOR SUB-OHM DEVICES.
**ERRONEOUS CONCENTRATION VALUES
**STORAGE (Sussman)
*Referring to: Tehrani MW, Ahererra AD, Tanda S, Chen R, Borole A, Goessler W, Rule AM. Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study. Journal of Environmental Exposure Assessment. 2023; 2(2): 9. http://dx.doi.org/10.20517/jeea.2023.03

===2022: Comments RE: [https://pubpeer.com/publications/C4BE0346C79DAAC7E1BB2DD6B6FAA3#1 Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence]===
*The reader may find the following commentary on Uguna & Snape by Chris Snowdon of interest. It includes a scientific review of the paper by Roberto Sussman that provides a convincing rebuttal of the author's assertions that heated tobacco products generate smoke. (Bates)
*Referring to: Uguna CN, Snape CE. Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence. ACS Omega. 2022 Jun 22;7(26):22111-22124. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260752/ doi: 10.1021/acsomega.2c01527]. PMID: 35811880; PMCID: PMC9260752.

===2022: Comments RE: [https://pubpeer.com/publications/CF1D17EA015361EED28A7886C21CC1#1 Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors]===
*"Conclusion. This study might be a correct and rigorous examination of various processes of the particulate phase of e-cigarette aerosol that are strictly valid under the abnormal overheating testing conditions. The study does not prove that such processes can occur in low powered devices, or even in high powered devices under the recommended power ranges and airflow rates normally used by consumers. The utility to assess the safety profile of e-cigarettes requires the devices to be tested under the best approximation possible to realistic usage. Unfortunately, this study failed to comply with this important consistency condition." (Sussman)
*Referring to: Dada O, Castillo K, Hogan M, Chalbot MG, Kavouras IG. Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors. Sci Rep. 2022 Nov 3;12(1):18571. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633786/ doi: 10.1038/s41598-022-21798-w]. PMID: 36329089; PMCID: PMC9633786.

===2017: Comments RE: [https://pubpeer.com/publications/6E2711F55673ADF831D636E2D701B9 "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions]===
*Multiple Comments
**"Users will operate the equipment in a way that does not lead to harsh dry puff conditions, with associated high VA formation. This is a key human control feedback that does not exist in laboratory equipment. So experiments that just standardise power settings or volume consumption must take care to validate these are realistic proxies for human use for a particular device. In this paper, many of the coil, power and volume settings combinations were not realistic. That could have been avoided through engaging with people with real practical expertise." (Bates)
**"In reality, as power to the coil increases, liquid consumption also increases. In real-world scenarios, human users regulate both power and liquid flow to minimise the risk of dry-puff conditions and therefore avoiding increases in VA emissions." (Barnes)
*Referring to: Soha Talih, Rola Salman, Nareg Karaoghlanian, Ahmad El-Hellani, Najat Saliba, Thomas Eissenberg, and Alan Shihadeh Chemical Research in Toxicology 2017 30 (10), 1791-1793 [https://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00212 DOI: 10.1021/acs.chemrestox.7b00212]

===2017: Comments RE: [https://pubpeer.com/publications/E5B66481CC847E532FEDB066434E92 Hidden formaldehyde in e-cigarette aerosols]===
*"The problem for the authors is that cancer is a human condition and their calculation is based exposures measured by a lab machine in conditions that no humans would be able to tolerate." (Bates)
*See also: [https://pubpeer.com/publications/5D8FB0EB72850380D1A37DAA2097D6 PubPeer 2015-2017]
**"Although Jensen et al. mentioned in the 2015 NEJM research letter that the health risks of formaldehyde hemiacetal inhalation are unknown ("How formaldehyde-releasing agents behave in the respiratory tract is unknown..."), they made a calculation that the formaldehyde-attributable cancer risk from e-cigarette use is 5 to 15 times higher than from long-term smoking. These two statements are clearly contradictory, and the calculation of any cancer risk from formaldehyde hemiacetal emissions is invalid since no such risk has been established for these compounds." (Farsalinos)
*See also: [https://pubmed.ncbi.nlm.nih.gov/28864295/ replication study]
**"The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided." (Farsalinos, Voudris, Spyrou, Poulas)
*See also 2015: [https://retractionwatch.com/2015/09/11/researchers-call-for-retraction-of-nejm-paper-showing-dangers-of-e-cigarettes/ Researchers call for retraction of NEJM paper showing dangers of e-cigarettes]
**Links to the efforts to have the referenced paper retracted.
*Referring to: Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. [https://www.nejm.org/doi/full/10.1056/nejmc1413069 doi: 10.1056/NEJMc1413069]. PMID: 25607446.

==Marketing / Social Media==

===2019: Comments RE: [https://www.juullabs.com/study-highlights-influence-of-illegal-compatible-products/ Characterising JUUL-related posts on Instagram]===
*A recent study in Tobacco Control relating to an analysis of “JUUL-related” Instagram posts contains serious factual errors and mischaracterizations of JUUL Labs’ historical social-media activity, falsely tying the company to the activities of manufacturers of “JUUL compatible” products that we believe are illegally on the market. (JUUL)
* [https://pubpeer.com/publications/B1DD80F0C868A59D609F0B9699E5F9 Additional comments]: In fact, a completely different story emerges from the data as qualified by Juul's statement. This is that FDA's failure to control newly-introduced Juul look-a-likes (which are illegal if introduced after 8 August 2016) is spawning a lawless industry driven by social media and in conflict with Juul's efforts to control sales of its products to youth. The study does not interrogate the underlying reality and I think Juul is right to react strongly. (Bates)
**Referring to: Czaplicki L, Kostygina G, Kim Y, Perks SN, Szczypka G, Emery SL, Vallone D, Hair EC. Characterising JUUL-related posts on Instagram. Tob Control. 2020 Nov;29(6):612-617. Epub 2019 Jul 2. PMID: 31266903. [https://doi.org/10.1136/tobaccocontrol-2018-054824 doi: 10.1136/tobaccocontrol-2018-054824]

==Multiple Outcomes==

===2024: Comments RE: [https://www.ecigarette-research.org/research/index.php/research/2024/281-ecig-disease Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===
*"The study provides zero evidence on any risk associated with e-cigarette use, whether absolute risk or in comparison with smoking. The question that was supposed to be addressed in this metanalysis CANNOT be examined with the studies included in their analysis." (Farsalinos)
*[https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 See Also]: "The methods look impressive, but the devil is in the dirty details buried in the nearly 100 pages supplemental material. The authors have done an admirable job collecting studies and organizing them, but the conclusions reached are untenable, and unsupportable at least for now." (Cummings)
**Referring to: Glantz SA, Nguyen N, Oliveira da Silva AL. Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes. NEJM Evid. 2024 Mar;3(3):EVIDoa2300229. Epub 2024 Feb 27. PMID: 38411454. [https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300229 doi: 10.1056/EVIDoa2300229]

===2024: Comments RE: [https://tobaccocontrol.bmj.com/content/33/3/373.responses#-comments-on-paper-by-asfar-et-al-%E2%80%9Crisk-and-safety-profile-of-electronic-nicotine-delivery-systems-ends-an-umbrella-review-to-inform-ends-health-communication-strategies%E2%80%9D Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies]===
*"Communicating health risk information about ENDS has to have some context to be meaningful to consumers. A common misconception about tobacco use is that the most dangerous component of the product is nicotine. However, while nicotine can be addictive, it is the other toxicants in tobacco, especially burned tobacco, that are the true culprits of tobacco-related diseases. Thus, when communicating information about the health risks of tobacco products, it makes sense to provide consumers with information about the relative health dangers from burned compared to unburned tobacco products. The example risk messages included in the supplementary materials to the paper appear to be developed with a goal of discouraging anyone from using a vaping product rather than to inform potential users about risks." (Cummings, Smith, Schroeder, Warner, McNeill, Hartmann-Boyce, Levy)
**Referring to: Asfar T, Jebai R, Li W, Oluwole OJ, Ferdous T, Gautam P, Schmidt M, Noar SM, Lindblom EN, Eissenberg T, Bursac Z, Vallone D, Maziak W. Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies. Tob Control. 2022 Sep 8:tobaccocontrol-2022-057495. doi: [https://tobaccocontrol.bmj.com/content/33/3/373 10.1136/tc-2022-057495]. Epub ahead of print. PMID: 36252567; PMCID: PMC10043882.

===2022: Comments RE: [https://colinmendelsohn.com.au/wp-content/uploads/2022/07/Mendelsohn-Wodak-Hall-Borland.-A-critical-analysis-of-Ecigs-and-health-outcomes-systematic-review-of-global-evidence.-DAR-2022.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]===
*Contrary to the conclusions of the Banks review, the evidence suggests that vaping nicotine is an effective smoking cessation aid; that vaping is substantially less harmful than smoking tobacco; that vaping is diverting young people away from smoking; and that vaping by smokers is likely to have a major net public health benefit if widely available to adult Australian smokers. (Mendelsohn)
**Referring to: Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. [https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022.

===2022: Comments RE: [https://pubpeer.com/publications/727EA7B64FB27270F20717729D7629 Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice]===
*Although this new research from Moshensky et al., does add to the scientific literature about previously marketed JUUL products, we believe the conclusions presented in the manuscript are not adequately supported by the study data. In addition, the lack of quantitative data on actual dosing limits the ability to establish relevance to potential human exposures from product use. Furthermore, the lack of a comparison against the effects of tobacco smoke limits the ability to evaluate these study findings in the context of the tobacco product risk continuum, and risk relative to use of combusted cigarettes. (Weil)
**Referring to: Moshensky A, Brand CS, Alhaddad H, Shin J, Masso-Silva JA, Advani I, Gunge D, Sharma A, Mehta S, Jahan A, Nilaad S, Olay J, Gu W, Simonson T, Almarghalani D, Pham J, Perera S, Park K, Al-Kolla R, Moon H, Das S, Byun MK, Shah Z, Sari Y, Heller Brown J, Crotty Alexander LE. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife. 2022 Apr 12;11:e67621. PMID: 35411847; PMCID: PMC9005188. [https://doi.org/10.7554/elife.67621 doi: 10.7554/eLife.67621]

===2018: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-modelling-study-on-electronic-cigarettes-in-the-us/ Quantifying population-level health benefits and harms of e-cigarette use in the United States]===
*"The authors make some very speculative assumptions here, particularly on the ‘gateway’ effect in teenagers – they assume that vaping leads to smoking. The trouble is, all their data on this comes from studies that don’t prove anything of the sort...The authors’ estimate of ‘life years lost’ is primarily driven by their overestimate of e-cig use contributing to a significant increase in the uptake of smoking in kids." (Shahab)
*"This new ‘finding’ is based on the bizarre assumption that for every one smoker who uses e-cigs to quit, 80 non-smokers will try e-cigs and take up smoking. It flies in the face of available evidence but it is also mathematically impossible." (Hajek)
**Referring to: Soneji SS, Sung HY, Primack BA, Pierce JP, Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS One. 2018 Mar 14;13(3):e0193328. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193328 doi: 10.1371/journal.pone.0193328]. PMID: 29538396; PMCID: PMC5851558.

==Respiratory==
*To learn more about Popcorn Lung, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Vaping_causes_Popcorn_Lung Myth: Vaping causes Popcorn Lung]

===2023: Comments RE: [https://pubpeer.com/publications/035039E269389CBFC88FCB9AFD225C#8 E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring]===
*Given all these shortcomings (opaqueness, unrealistic airflow and nicotine, likely overexposure of mice), the results of this study are not reliable to assess potential harms from exposure to e-cigarette aerosol. (Sussman)
*Referring to: Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, Miller RA, Wold LE, Gorr MW. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L676-L682. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722245/ doi: 10.1152/ajplung.00233.2022]. Epub 2022 Oct 11. PMID: 36218276; PMCID: PMC9722245.

===2022: Comments RE: [https://pubpeer.com/publications/D93498039BF8D05DFAE58BFC29DD1B The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Therefore, it is deficient and unreliable." (Rodu)
*Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019 Oct 16;19(1):180. [https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0950-3 doi: 10.1186/s12890-019-0950-3]. PMID: 31619218; PMCID: PMC6796489.

===2022: Comments RE: [https://pubpeer.com/publications/075B90E6B4FEB1AF3BB188690C317F Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017]===
*"The study by Osei et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Osei, A. D., Mirbolouk, M., Orimoloye, O. A., Dzaye, O., Uddin, S. M. I., Benjamin, E. J., Hall, M.E., DeFilippis, A.P., Bhatnagar, A., Biswal, S.S., Blaha, M. J. (2020). Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017. American Journal of Preventive Medicine. [https://www.ajpmonline.org/article/S0749-3797(19)30479-9/fulltext https://doi.org/10.1016/j.amepre.2019.10.014]

===2022: Comments RE: [https://pubpeer.com/publications/8993443E1BA20DF0D8F4E1F51DFB79 Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data]===
*"The study by Wills et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Wills TA, Choi K, Pokhrel P, Pagano I. Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data. Prev Med. 2022 Aug;161:107137. [https://www.sciencedirect.com/science/article/abs/pii/S0091743522001864 doi: 10.1016/j.ypmed.2022.107137]. Epub 2022 Jul 9. PMID: 35820496; PMCID: PMC9328844.

===2022: Comments RE: [https://pubpeer.com/publications/7B80EB6A718B6A0F2B4634DFE56886 E-cigarette use and respiratory disorder in an adult sample]===
*"Their study used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
*Referring to: Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019 Jan 1;194:363-370. [https://www.sciencedirect.com/science/article/abs/pii/S0376871618307622 doi: 10.1016/j.drugalcdep.2018.10.004]. Epub 2018 Nov 7. PMID: 30472577; PMCID: PMC6312492.

===2022: Comments RE: [https://pubpeer.com/publications/9946B2A97F6F6AF0F898D95F7CB23D E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report]===
*"The problem with these studies is disentangling the effects of a smoking career (something more complicated than adjusting for current-, former-, never-smoking status) and subsequent vaping behaviour. Also, the relationships are complicated by reverse causation (was the vaping a response to smoking-induced respiratory symptoms?), a hard-to-define counterfactual (has the vaping displaced smoking or displaced abstinence?), and the fact that respiratory damage arises from cumulative exposure and vaping exposures may be adding incremental risk (would the subject have any symptoms if they hadn't smoked first?)." (Bates)
*Referring to: Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 Dec 1;17(12):e0269760. [https://pubmed.ncbi.nlm.nih.gov/36454742/ doi: 10.1371/journal.pone.0269760]. PMID: 36454742; PMCID: PMC9714717.

===2020: Comments RE: [https://pubpeer.com/publications/EF05B531214379DD314797A20F2D9D Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?]===
*"The problem is that vegetable glycerin (glycerol) is not a lipid it is an alcohol. It cannot cause the lipoid pneumonia symptoms mentioned." (Bates)
*"Endogenous lipoid pneumonia from VG (or PG) inhalation is a speculation and implausible...The experience in the US over the past several months clearly shows that the culprit for the acute lung intoxication cases are black market THC oils which were sold as THC oils, not e-cigarette products." (Farsalinos)
*"visual assessment of lung HRCT scans showed no pathological findings in people vaping daily for more than 3.5 years. In particular, no CT features compatible with early signs of COPD (i.e. parenchymal micronodules, ground-glass opacity, or macroscopic emphysema) or lipoid pneumonia or popcorn lung disease were present." (Polosa)
*Referring to: Eissenberg T, Maziak W. Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury? Am J Respir Crit Care Med. 2020 Apr 15;201(8):1012-1013. [https://pubmed.ncbi.nlm.nih.gov/31917600/ doi: 10.1164/rccm.201910-2082LE]. PMID: 31917600; PMCID: PMC7159422.

===2019-2020: Comments RE: [https://pubpeer.com/publications/7571819CEB7A2BC425BE3D7061410D Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis]===
*Multiple Comments:
**"One of the essential criteria of causal inference is that exposure to the cause precedes disease onset. Three of the diseases Glantz studies — COPD, chronic bronchitis and emphysema — take decades to become clinically apparent and would have been present, even though undiagnosed, in many of his cases long before his study began in 2014, and indeed even before e-cigarettes first became available in the US in about 2007. His findings are also flawed by the fact that most vapers have smoked, and since smoking is a strong cause of chronic lung disease, vapers inevitably carry an increased risk of lung disease long after quitting smoking. Glantz claims to have allowed for this statistically but his approach is simplistic: he lacks the detail of lifetime duration and intensity of smoking required. On these grounds alone his conclusion is specious." (Britton)
**"Donald Kenkel and colleagues at Cornell University conducted a replication of the analysis using econometric techniques...When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco." (Bates)
*Referring to: Bhatta DN, Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020 Feb;58(2):182-190. [https://www.ajpmonline.org/article/S0749-3797(19)30391-5/fulltext doi: 10.1016/j.amepre.2019.07.028]. Epub 2019 Dec 16. PMID: 31859175; PMCID: PMC6981012.

===2019: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-ecig-vapour-and-cancer-in-mice/ Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice]===
*Multiple comments:
**“The comparison between mice breathing vapour and mice breathing air is not statistically significant. There is no sample size justification and no power calculation. There is no message to the public here – I suspect these results are just noise.” (Britton)
**“The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures. The authors assigned the effects they observed to a carcinogen NNK – but NNK has been measured before in human vapers, and it is known that exposure from vaping is either negligible or none.” (Hajek)
*Referring to: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. [https://pubmed.ncbi.nlm.nih.gov/31591243/ doi: 10.1073/pnas.1911321116]. Epub 2019 Oct 7. Erratum in: Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22884. PMID: 31591243; PMCID: PMC6815158.

===2017: Comments RE: [https://pubpeer.com/publications/41F6EA57D0803EEE9DF65162DF0097 Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts]===
*"It is literally true that they "find no evidence...", but that is because this study is completely ill-suited to drawing any policy conclusions about e-cigarettes and COPD. Despite hinting at the limitations of cross-sectional data, the authors draw a negative-sounding conclusion without addressing the key question of how respiratory health changes for a given smoker who uses e-cigarettes to quit or cut down once they are ill from smoking or as a way of preventing COPD." (Bates)
*Referring to: Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. [https://pubmed.ncbi.nlm.nih.gov/28884423/ doi: 10.1007/s11606-017-4150-7]. Epub 2017 Sep 7. PMID: 28884423; PMCID: PMC5698219.

===2016: "Popcorn Lung" Comments RE: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892932/ Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes”]===
**"Over the past five years, we have published the results of several studies in which diacetyl and 2,3-pentanedione levels were measured in various consumer products..."
**"..."hundreds of consumer products (e.g., tea, coffee, citrus juices, butter) contain naturally occurring diacetyl and 2,3-pentanedione...several studies have shown that airborne diketones associated with these products are easily detectable..."
**"Unless one assumes that unflavored coffee beans pose a serious risk of “popcorn lung,” a rare and oftentimes lethal disease, then one should agree that exposures to airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk."
**"Similarly, we measured concentrations of naturally occurring diacetyl and 2,3-pentanedione in mainstream cigarette smoke at levels (200–400 ppm and 30–50 ppm, respectively) that are hundreds of thousands of times higher than the NIOSH and ACGIH OELs, yet cigarette smoking is not associated with “popcorn lung”. Also, as others have noted, diketone exposures from traditional cigarettes are higher than those associated with e-cigarette use, hence switching from tobacco to e-cigarettes may result in reduced diketone exposure."
**"Ironically, suggesting that diketone levels in e-cigarettes are potentially dangerous could actually lead to higher diketone exposures in the smoking population if smokers decide not to switch to e-cigarettes due to as yet unfounded health concerns." (Pierce, Abelmann, Finley) For further information, see authors [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892901/ response] to the comments above.
*See Also: 2016: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892907/ On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings]
**"The 51 e-juices sampled make up a very small proportion of all the products sold, and there is variability in the chemical content of specific products as well as how those chemicals are delivered by different devices. The authors therefore acknowledge that it is impossible to extrapolate their results to all the other products on the market. Importantly, this study did not assess levels of diacetyl, 2,3-pentanedione, and acetoin in actual users, much less health effects. So it’s premature to assume that exposure to these chemicals via e-cigarettes causes health problems." (Arnold)
*See Also: 2015: [https://rodutobaccotruth.blogspot.com/2015/12/is-harvard-e-cigarette-buttery-flavor.html Is the Harvard E-Cigarette Buttery Flavor Study Credible?]
**"As I advised previously, vapers should only use liquids that are certified to be free of buttery flavors that are suspected respiratory toxicants. However, laboratory investigations of e-cigarettes should use validated methods to assure credibility. The results of the Harvard Buttery Flavor Study do not meet this standard." (Rodu)
*See Also: 2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/236-da2 A new study finds diacetyl in e-cigarettes but exaggerates risks and fails to discuss about smoking]
**"In conclusion, the article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes. They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk." (Farsalinos)
*See Also: 2015: [https://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking]
**"Nevertheless, it is disingenuous and actually damaging to the public's health to spread the message that vaping causes fatal lung disease or even that it appears to increase the risk for popcorn lung. And it is especially disingenuous and damaging to send these messages to the public without telling us that smoking produces exposure to diacetyl that is on average about 750 times higher than vaping." (Siegel)
*Referring to: Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 2016 Jun;124(6):733-9. [https://pubmed.ncbi.nlm.nih.gov/26642857/ doi: 10.1289/ehp.1510185]. Epub 2015 Dec 8. PMID: 26642857; PMCID: PMC4892929.

===2016: Comments RE: [https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===
*"The mice were severely overdosed with nicotine, up to the lethal levels for mice, and a huge amount above what any human vaper would get...Regarding the relevance to human health, nicotine poisoning poses normally no risk to vapers or smokers because if nicotine concentrations start to rise above their usual moderate levels, there is an advance warning in the form of nausea which makes people stop nicotine intake long before any dangerous levels can accrue. (Mice in these types of experiments do not have that option)." (Hajek)
*Referring to: Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax. 2016 Dec;71(12):1119-1129. [https://pubmed.ncbi.nlm.nih.gov/27558745/ doi: 10.1136/thoraxjnl-2015-208039]. Epub 2016 Aug 24. PMID: 27558745; PMCID: PMC5136722.

===2015: Comments RE: [https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/5dfe1e98-3100-4102-a425-a647b9459456 Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model]===
*" In other words, to obtain the same exposure in humans the e-cig user should take 11000 – 13000 puffs per day. Assuming 8 hours of sleep per day, in order to acquire such a high number of puffs e-cig users would need to take 11-13 puffs per minute and thus practically take an e-cig puff with each breath. In conclusion we recommend that the results of the discussed study should be interpreted with caution and that more studies with more realistic levels of e-liquid exposure should be conducted." (Mukhin, Rose)
*Referring to: Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. (2015) Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. PLoS ONE 10(2): e0116861. https://doi.org/10.1371/journal.pone.0116861

=Retractions by Journal=

===2025: Comments RE: [https://academic.oup.com/ntr/article/28/2/314/8320356 Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review]===
*Therefore, the Editor is retracting this article because the article was accepted with an undisclosed conflict of interest that would have changed the editorial decision.
**Referring to: Xingyu Liu, Rana Tayyarah, Xiang Chang, Xin Gao, Lisha Chen, Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review, Nicotine & Tobacco Research, 2025; ntaf189, https://doi.org/10.1093/ntr/ntaf189.

===2024: Comments RE: [https://www.science.org/content/article/questionable-firms-tempt-young-doctors-with-easy-publications Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES]===
*"The more they looked at the article, the more problems they saw. The work was based on data from an annual survey on health and nutrition by the U.S. Centers for Disease Control and Prevention (CDC), but the reported number of survey respondents was inexplicably off by an order of magnitude—the survey is completed by about 5000 people a year, but the paper cited 266,058 respondents from 2015 to 2018. The authors also failed to report whether the difference in age of stroke onset between vapers and traditional smokers could simply be due to vapers being younger overall. And those were just a few of the obvious issues, according to Cohen and Foxon, who alerted both the authors and the journal to their concerns." (Joelving)
*See Also: [https://twitter.com/FloeFoxon/status/1786522387338465755 Tweetorial] (Foxon) and [https://pubpeer.com/publications/1F118DC9A92A4FC13507BB5448462D PubPeer] (Richardson and others - 4 comments)
*Retracted: 18th of December, 2025
**Referring to: Patel U, Patel N, Khurana M, Parulekar A, Patel A, Ortiz JF, Patel R, Urhoghide E, Mistry A, Bhriguvanshi A, et al. Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES. Neurology International. 2022; 14(2):441-452. https://doi.org/10.3390/neurolint14020037

===2022: Original: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239491/ Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study]===
*Citation: RC, Dawoodi S, Fabara SP, Asad M, Khayyat A, Chandramohan S, Aslam A, Unachukwu N, Nasyrlaeva B, Jaiswal R, Chowdary SB, Malik P, Rabbani R. Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study. Gastroenterology Res. 2022 Jun;15(3):113-119. doi: 10.14740/gr1490. Epub 2022 Jun 22. Retraction in: Gastroenterology Res. 2023 Jun;16(3):201. PMID: 35836707; PMCID: PMC9239491.
*2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284643/ Retraction Notice to “Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study”]
**Media - Filter: [https://filtermag.org/vaping-liver-disease-study-retracted/ Journal Retracts Study That Linked Vaping to Liver Disease]

===2022: Original: [https://reason.com/wp-content/uploads/2023/01/1438-9260-6-PB.pdf Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study]===
*Citation: Chidharla A, Agarwal K, Abdelwahed S, Bhandari R, Singh A, Rabbani R, Patel K, Singh P, Mehta D, Manaktala PS, Pillai S, Gupta S, Koritala T. Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study. World J Oncol. 2022 Feb;13(1):20-26. doi: 10.14740/wjon1438. Epub 2022 Feb 8. Retraction in: World J Oncol. 2022 Dec;13(6):417. PMID: 35317331; PMCID: PMC8913014.
*2022: [https://reason.com/wp-content/uploads/2023/01/1562-10357-1-PB.pdf Retraction Notice to “Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study”]
**Media - Reason: [https://reason.com/2023/01/04/a-medical-journal-retracts-a-2022-study-that-linked-vaping-to-cancer/ A Medical Journal Retracts a 2022 Study That Linked Vaping to Cancer]

===2019: Original: [https://www.ahajournals.org/doi/10.1161/JAHA.119.012317 Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]===
**Citation: Bhatta DN, Glantz SA. Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health. J Am Heart Assoc. 2019 Jun 18;8(12):e012317. doi: 10.1161/JAHA.119.012317. Epub 2019 Jun 5. Retraction in: J Am Heart Assoc. 2020 Feb 18;9(4):e014519. Erratum in: J Am Heart Assoc. 2019 Nov 5;8(21):e002313. PMID: 31165662; PMCID: PMC6645634.
*2020: [https://www.ahajournals.org/doi/10.1161/JAHA.119.014519 Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]
**[https://pubpeer.com/publications/F177153E02CA8B3E7B9E70BC8DB204 PubPeer]
**Media - USA Today: [https://www.usatoday.com/story/news/health/2020/02/20/nyu-scientists-others-call-taxpayer-funded-ucsf-vaping-study-probe/4805323002/ A study claimed vaping doubles risk for heart attacks. It's been retracted for being 'unreliable']

===2019: Original: [https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.29148 Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non–small cell lung cancer]===
**Citation: Liu Z, Lu C, Zhao G, Han X, Dong K, Wang C, Guan JZ, Wang Z. Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non-small cell lung cancer. J Cell Biochem. 2019 Oct;120(10):18370-18377. doi: 10.1002/jcb.29148. Epub 2019 Jun 12. Retraction in: J Cell Biochem. 2024 Apr 5. doi: 10.1002/jcb.30562. PMID: 31190333.
*[https://pubmed.ncbi.nlm.nih.gov/38577886/ PubMed Retraction]
*Retracted 2024: [https://pubpeer.com/publications/D500DE74010B291A7B27CBB9083FEA PubPeer Comment about retraction]

=Retractions by Author Request=

===2025: [https://link.springer.com/article/10.1038/s41388-024-03269-w Retraction Note: Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis]===
"The authors have retracted this article. After publication, concerns were raised regarding highly similar ex vivo brain images in Figs. 2A (Vehicle, right), 5A (miR-4466 inh., left) and 6E (-Nic.+Stat3i, right). The authors thoroughly checked the underlying data and found that the data were mismanaged, which may have affected the presented results.
**Citation: Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R, Singh R, Li W, Topaloglu U, Ruiz J, Watabe K. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022 May;41(22):3079-3092. doi: 10.1038/s41388-022-02322-w. Epub 2022 Apr 23. Retraction in: Oncogene. 2025 Jan 9. doi: 10.1038/s41388-024-03269-w. PMID: 35461327; PMCID: PMC9135627.

===2024: [https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00998-w The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis]===
**Citation: Tehrani, H., Rajabi, A., Ghelichi- Ghojogh, M. et al. RETRACTED ARTICLE: The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis. Arch Public Health 80, 240 (2022). https://doi.org/10.1186/s13690-022-00998-w
*[https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-024-01345-x Retraction Notice]: The authors have retracted this article because it incorrectly reports the results of several studies included in their review. This impacts the overall results of their meta-analysis. The authors have been offered the opportunity to re-analyse their findings and to submit an updated version to the journal, which will be subjected to robust peer review.

===2024: [https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814489 RETRACTED: Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking A Randomized Clinical Trial]===
**Citation: Liu Z. Notice of Retraction: Lin HX et al. Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. 2024 May 1;184(5):589. doi: 10.1001/jamainternmed.2024.1125. PMID: 38551593.
*[https://pubpeer.com/publications/A3736116C180E920966659A2AEA32F Author's retraction request post on PubPeer]
*Retraction Watch: [https://retractionwatch.com/2024/04/02/paper-claiming-vaping-tops-nicotine-gum-for-smoking-cessation-retracted-from-jama-journal/ Paper claiming vaping tops nicotine gum for smoking cessation retracted from JAMA journal]

=Articles/Blogs=

===2026: [https://rogerbate.substack.com/p/retractions-dont-repeal-regulation Retractions Don’t Repeal Regulation: How Suspect—and Occasionally Fraudulent—Evidence Shapes Tobacco Harm Reduction Policy]===

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*[https://www.coehar.org/anti-vaping-narrative-driven-by-low-quality-science-goes-undetected-by-editorial-quality-checks/ Anti-vaping narrative driven by low quality science goes undetected by editorial quality checks]

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===[https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===

===2025: RE [https://www.pubpeer.com/publications/B604AE5B635D7A1A0E0A6571FDEF16 Exposure to third hand e-cigarette vapour impairs cognitive function in young mice]===

===2025: [https://www.qeios.com/read/FDX7P3 Exposure to Benzene, Toluene, and Xylenes from Electronic Cigarette Use Compared to Working Environment Permissible Exposure Limits: A Risk Assessment Analysis of a Recent Publication]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntae232/7780360?login=false Electronic cigarettes during pregnancy: Another tool for discontinuing smoking?]===
*note: this isn't formatted for placement in the correct section
*[https://x.com/ArielleSelya/status/1839786888099463656 Twitter thread]

===2025: [https://www.qeios.com/read/9XT2GU Critical Appraisal of Exposure Studies on E-Cigarette Aerosols Generated by High-Powered Devices]===
*note: this isn't formatted for placement in the correct section

===[https://pubmed.ncbi.nlm.nih.gov/31712273/ Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes]===
*note: this isn't formatted for placement in the correct section
*[https://www.sciencemediacentre.org/expert-reaction-to-case-study-linking-lung-inflammation-to-vaping-in-a-16-year-old/ Expert Comments]

===Paper: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00253 Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]===
*Comment: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00367 Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]
*Response: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00414 Response to Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]

===Paper: [https://gh.bmj.com/content/9/2/e013866 Pharmaceuticalisation as the tobacco industry’s endgame]===
*Comment: [https://pubpeer.com/publications/374B1C6D333BD84814E878DF9D1611 Title: Errors in one sentence - oversights or indicators of other problems?]

===[https://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/233-pm A new study reports that e-cigarettes emit toxins to the environment but the authors did not really find any…]===

 

[[File:Retracted 2.png|center|]]
[[Category:Studies, Surveys, and Papers]]

ENDS Cancer

2026-04-26T11:12:51Z

Skip: /* Suggested studies to add to this page */

'''Studies, Surveys, Papers, and Case Studies'''
*Sometimes it's necessary to view the PDF version to access the full study.
*This page is for referencing the possible benefits of [[Abbreviations|'''ENDS''']] products vs. smoking cigarettes from a Cancer standpoint. (Electronic Nicotine Delivery Systems are also known as vapor technology, ecigarettes, ecigs, EVP, etc.)
*If you'd prefer someone else to add a study to a topic, there is a subject section called "Suggested studies to add to this page". You may put the link in that section for one of the regular page editors to address.

=Studies=

===2020: [https://link.springer.com/article/10.1007/s00204-020-02924-x Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products (HTPs) and electronic cigarettes (ECs) aerosols with cigarette smoke]===
*Even if they should not be considered as risk-free products, however, HTPs and ECs lead to an appreciable risk reduction in comparison to cigarettes, both for cancer and non-cancer diseases. According to the current knowledge, and more specifically to the data presented here, HTPs and ECs might be considered as an acceptable reduced risk substitute for cigarettes for legal-age smokers who would otherwise continue smoking cigarettes.
*A more pronounced cancer risk reduction was observed when comparing the mean lifetime cancer risk for the considered ECs with that for cigarette smoke. This reduction was about two orders of magnitude (ratio of 0.009 and 0.014) with 2.42·10–4 and 3.95·10–4 for ECs compared to 2.73·10–2 for cigarettes. In terms of consumers, this would mean that 1 out of 36 cigarette smokers vs. 1 out of 4132 or 1 out of 2531 EC consumers may develop a cancer if the cancer root cause would be only associated with exposure to the considered HPHCs.
*[https://link.springer.com/content/pdf/10.1007/s00204-020-02924-x.pdf PDF Version]
*Citation: Rodrigo, G., Jaccard, G., Tafin Djoko, D. et al. Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke. Arch Toxicol 95, 283–298 (2021). doi: 10.1007/s00204-020-02924-x
*Acknowledgement: Philip Morris International is the sole source of funding and sponsor of this research.

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043356/ Electronic cigarette use among patients with cancer: Reasons for use, beliefs, and patient-provider communication]===
*Smoking tobacco cigarettes after a cancer diagnosis increases risk for several serious adverse outcomes. Thus, patients can significantly benefit from quitting smoking. Electronic cigarettes are an increasingly popular cessation method.
*Patients with cancer who use e-cigarettes have positive attitudes toward these devices and use them to aid in smoking cessation. Most participants identified smoking cessation as the reason for initiating (81%) and continuing (60%) e-cigarette use.
*Patients characterized e-cigarettes as more satisfying, more useful for quitting smoking, and more effective at reducing cancer-related stress than nicotine replacement therapies.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043356/pdf/nihms967690.pdf PDF Version]
*Citation: Correa JB, Brandon KO, Meltzer LR, et al. Electronic cigarette use among patients with cancer: Reasons for use, beliefs, and patient-provider communication. Psychooncology. 2018;27(7):1757-1764. doi:10.1002/pon.4721
*Acknowledgement: National Cancer Institute, Grant/Award Numbers: R01 CA154596 and P30CA76292

===2017: [https://tobaccocontrol.bmj.com/content/27/1/10 Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke]===
*Most e-cigarette analyses indicate cancer potencies <1% that of tobacco smoke and <10% that of a heat-not-burn prototype, although a minority of analyses indicate higher potencies.
*Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke.
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/27/1/10.full.pdf PDF Version]
*Citation: Stephens WEComparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smokeTobacco Control 2018;27:10-17.
*Article in Lung Disease News: [https://lungdiseasenews.com/2017/08/25/study-finds-that-cancer-risk-of-e-cigarettes-is-much-lower-than-that-of-cigarette-smoke/?fbclid=IwAR1qEBP2dW4ccXc0fUEWpZIR6ZpsBJwMw-tDsB_PFiiHgR4XaJRaIAbutl4 E-Cigarettes Carry Much Less Risk of Lung Cancer Than Cigarette Smoke, Study Finds]

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435921/ Comparative tumor promotion assessment of e‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay]===
*Results from this study suggest that e‐cigarettes may have reduced tumor promoter activity compared to conventional cigarettes and therefore may provide a safer alternative to cigarettes.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435921/pdf/EM-58-190.pdf PDF Version]
*Citation: Breheny D, Oke O, Pant K, Gaça M. Comparative tumor promotion assessment of e-cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay. Environ Mol Mutagen. 2017;58(4):190-198. doi:10.1002/em.22091
*Acknowledgement: The authors are employees of British American Tobacco or BioReliance Corporation. BioReliance conducted all experimental work and were funded by British American Tobacco. Nicoventures, UK, is a wholly‐owned subsidiary of British American Tobacco.

===2017: [https://tobaccocontrol.bmj.com/content/26/e1/e23.long Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation (G2) and third-generation (G3) electronic cigarette users]===
*While not harmless, electronic cigarettes (e-cigarettes) have demonstrated a much more favourable toxicological profile than combustible cigarettes—the worldwide leading cause of preventable death. Average eCO levels (ppm) were significantly higher in smokers than in e-cigarette users. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant.
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/26/e1/e23.full.pdf PDF Version]
*Citation: Wagener TL, Floyd EL, Stepanov I, et alHave combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette usersTobacco Control 2017;26:e23-e28.
*Acknowledgement: Intramural funds to TLW were used to complete this study. Part of TLW's, ELF's, LMD's, ELL's, NM's, APT's, and LQ's salary support is provided by the Oklahoma Tobacco Research Center, which is provided funding from the Oklahoma Tobacco Settlement Endowment Trust. The Oklahoma Shared Clinical and Translational Resources (U54 GM104938) provided phlebotomy support to this study.

===2017: [https://www.acpjournals.org/doi/10.7326/M16-1107 Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study]===
*Conclusion: Former smokers with long-term e-cigarette–only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette–only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.
*[https://sci-hub.se/10.7326/M16-1107 PDF Version]
*Citation: Shahab, L., Goniewicz, M. L., Blount, B. C., Brown, J., McNeill, A., Alwis, K. U., … West, R. (2017). Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users. Annals of Internal Medicine, 166(6), 390. doi:10.7326/m16-1107
*Acknowledgement: Funding: Cancer Research UK

===2016: [https://www.lungcancerjournal.info/article/S0169-5002(16)30323-3/fulltext Patients with lung cancer: Are electronic cigarettes harmful or useful?]===
*Based on current knowledge, for patients with lung or other forms of cancer who would otherwise continue to smoke, e-cigarettes offer an alternative way to quit smoking while they undergo medical treatment. The option to switch to e-cigarettes should be considered by healthcare practitioners with patients with cancer who would otherwise continue to smoke.
*No free version of PDF found
*Citation: Dautzenberg, B., & Garelik, D. (2017). Patients with lung cancer: Are electronic cigarettes harmful or useful? Lung Cancer, 105, 42–48. doi:10.1016/j.lungcan.2016.05.011

=Suggested studies to add to this page=

===2026: [https://pubmed.ncbi.nlm.nih.gov/42021215/ Effect of electronic cigarette aerosols on cisplatin resistance in head and neck cancer cells: a collaborative replication study]===

=More Information=
*Click on the category link below for more studies by topic on ENDS and Nicotine.
[[Category:Studies, Surveys, and Papers]]

ENDS Flavors

2026-04-26T10:56:13Z

Skip:

[[File:ENDS Flavors.jpg|center]]
 

<languages/>
<translate>

It's often necessary to view the PDF version to access the full study. If you'd like to contribute to this page, please see the instructions at the bottom of the page.


Suggestions welcome!

=Personal Testimonies from people who used to smoke & Blogs= 

===All Years: Video Collection: [https://www.youtube.com/channel/UCY3vMuTdXfL7Z4PAsx7Q5nA/videos Golden Oldies Capitol Tours]=== 


*People who used to smoke share how long they smoked and what flavors helped them to quit smoking.

===All Years: Collection 13,000+ Testimonies: [https://casaa.org/_testimonials/ CASAA - REAL PEOPLE. REAL STORIES.]=== 


*Online submissions of personal testimonies by people who switched from smoking to harm reduction products.

===2021: Letter: [https://clivebates.com/documents/CanadaFlavourBanSept2021.pdf Proposed vaping products’ flavour regulations – a response]===
*This submission responds to Health Canada’s Consultation on Proposed vaping products’ flavour regulations and order and related regulatory impact analysis.

===2021: Letter: [https://clivebates.com/documents/NLFlavoursResponseJan2021.pdf Regulation of e-cigarette flavours – a response]===
*This document responds to the proposed Decree of the State Secretary for Health, Welfare and Sport on the regulation of e-cigarette flavours in the Netherlands. We provide a summary followed by a detailed discussion of each of the twelve sections in the summary.

===2021 Blog: [http://mommavape.blogspot.com/2021/06/gummy-bears-and-cotton-candy.html Gummy Bears and Cotton Candy]===
*The voice of consumers who are trying to quit smoking continues to be ignored. The use of flavored e-cigarettes was associated with more than twice the odds of smoking cessation among adult users compared to those using tobacco flavors. History demonstrates the adult love of all things candy. If something candy flavored is what helps someone stop smoking, who are we to tell them they can't quit that way?

===2019 Blog: [https://clivebates.com/the-us-vaping-flavour-ban-twenty-things-you-should-know/ The US vaping flavour ban: twenty things you should know]===
*What is the chance that this level of adult panic is, in fact, driving the very behaviour it is worrying about?

===2017 Blog: [http://mommavape.blogspot.com/2017/05/cotton-candy-is-not-marketing-to-kids.html Cotton Candy is NOT Marketing To Kids]=== 


*She says "honey, you need to get with the program, we were too poor when I was a kid to afford cotton candy, so now I'm having it whenever I want and any way I want it. Now give me the sweetest thing you got and I want cotton candy the next time I come here."
*"Ma'am, if you don't mind me asking, how old are you?". She looks at me and says "82, I quit smoking 6 months ago and now I'm going to live to be 102."

===2017 Blog: [https://clivebates.com/flavors Are e-liquid flavours really “hooking another generation of kids”?]===
*To evaluate the demand to regulate these flavours (by which they mean ban them) you first need a framework for thinking about the issue – and that is not simple and may yield surprises.

=Abuse Liability - All THR Products= 

===See Also: [https://safernicotine.wiki/mediawiki/index.php/Nicotine_-_Addiction/Dependence Nicotine - Addiction/Dependence]===

===2022: [https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-14166-w E-cigarette addiction and harm perception: Does initiation flavor choice matter?]===
*"Traditionally flavored e-cigarette initiation produces similar risk for addiction and harm perceptions as non-traditionally flavored initiation. These findings suggest that banning non-traditional flavors alone may be ineffective in curbing e-cigarette addiction and harm perception. Additional research is needed to better understand which e-cigarette product characteristics and behaviors may be associated with greater addiction and reduced harm perceptions."
**Hung, M., Spencer, A., Hon, E.S. et al. E-cigarette addiction and harm perception: Does initiation flavor choice matter?. BMC Public Health 22, 1780 (2022). https://doi.org/10.1186/s12889-022-14166-w

===2022: [https://academic.oup.com/ntr/article/24/9/1332/6550857 The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review]===
*"E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers."
**Citation: Mari S Gades, Aleksandra Alcheva, Amy L Riegelman, Dorothy K Hatsukami, The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review, Nicotine & Tobacco Research, Volume 24, Issue 9, September 2022, Pages 1332–1343, https://doi.org/10.1093/ntr/ntac073
***Acknowledgment: This work was supported by the National Institute of Drug Abuse (T32 DA007097 and R36 DA050000 to MSG); and the National Institutes of Health (P01 CA217806 to DKH).

===2020: [https://pubmed.ncbi.nlm.nih.gov/33176942/ Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers]=== 


*Controlled use of JS (JUUL System) among adult smokers resulted in nicotine delivery, product liking, and satisfaction that were less than that of combustible cigarettes but generally greater than nicotine gum. These results support the conclusion that JS has lower abuse liability than combustible cigarettes, higher abuse liability than nicotine gum, and may provide sufficient nicotine delivery and satisfying effects to support substitution for combustible cigarettes among adult smokers.
*[https://www.sciencedirect.com/science/article/pii/S0376871620305603 PDF Version]
*Citation: Nicholas I. Goldenson, August R. Buchhalter, Erik M. Augustson, Mark L. Rubinstein, Jack E. Henningfield, Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers, Drug and Alcohol Dependence, Volume 217, 2020, 108395, ISSN 0376-8716, doi:10.1016/j.drugalcdep.2020.108395.

===2003: [https://pubmed.ncbi.nlm.nih.gov/12616334/ Subjective effects of the nicotine lozenge: assessment of abuse liability]=== 


*In conclusion, results of the present study suggest that abuse liability of nicotine lozenges is low. Low abuse liability of the novel nicotine lozenges is in accordance with current knowledge of consumer use patterns of other, already marketed nicotine replacement therapies, which suggest little abuse of these products once they are marketed. Dose-dependent craving reduction by the lozenges in adults (22–50 years) but not young adults (18–21 years) suggests efficacy of the lozenge for adults, and reinforces the need for further studies of nicotine delivery systems as a treatment for nicotine dependence in younger adults and adolescents
*[https://sci-hub.se/10.1007/s00213-002-1361-2 PDF Version]
*Citation: Houtsmuller, E. J., Henningfield, J. E., & Stitzer, M. L. (2003). Subjective effects of the nicotine lozenge: assessment of abuse liability. Psychopharmacology, 167(1), 20–27. doi:10.1007/s00213-002-1361-2

===2002: [https://pubmed.ncbi.nlm.nih.gov/12175452/ Flavor improvement does not increase abuse liability of nicotine chewing gum]=== 


*Improved flavor of nicotine gum does not increase abuse liability, but may be associated with enhanced craving reduction.
*mint-flavored nicotine gum was rated as more palatable than the original nicotine gum, but the improvement in flavor did not increase abuse liability in adults (22 – 50 years old) or young adults (18 –21 years old). Since the aversive taste of the original nicotine gum was an important impediment to compliance (Rose, 1996) and treatment initiation, the availability of nicotine gum in different flavors and the development of alternative oral nicotine replacement products with appealing flavors may improve compliance and expand the range of options for those attempting to quit smoking, without posing an increased risk of abuse.
*[https://sci-hub.se/10.1016/s0091-3057(02)00723-2 PDF Version]
*Citation: Houtsmuller, E. J., Fant, R. V., Eissenberg, T. E., Henningfield, J. E., & Stitzer, M. L. (2002). Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacology Biochemistry and Behavior, 72(3), 559–568. doi:10.1016/s0091-3057(02)00723-2

=Marketing/Advertising/Packaging=

===2024: [https://www.tandfonline.com/doi/full/10.1080/10826084.2024.2374973 Associations Between Noticing E-Cigarette Advertising Features and E-Cigarette Appeal and Switching Interest Among Young Adult Dual Users]===
*Results: "Noticing fruit flavors (AOR = 1.67 and 1.28) and fruit images (AOR = 1.53 and 1.21) was positively associated with having any e-cigarette product appeal and switching interest. Noticing price promotions (AOR = 1.23) was positively associated with product appeal. In contrast, noticing nicotine warnings (AOR = 0.74 and 0.86), smoker-targeted claims (AOR = 0.78 and 0.89), and tobacco flavors (AOR = 0.92 and 0.90) was negatively associated with product appeal and switching interest."

=Multiple Points=

===2022: [https://media.thr.net/strapi/34d52398d9056adece15e8bda5172870.pdf?updated_at=2023-08-29T12:28:33.423Z THE CASE FOR FLAVOURS IN TOBACCO HARM REDUCTION, TO SAVE LIVES]===
*This 2022 updated review evaluates the use of flavours in THR products, specifically, nicotine vaping products. It highlights the link between (flavoured) vaping products and smoking cessation, and the potential benefits and risks of flavours and their availability for public health.

=Public Health Advantages / Concerns of Public Health Harms= 

===2023: [https://www.sciencedirect.com/science/article/abs/pii/S0378427423001091 A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro]===
*"We show that the tested flavours do not increase overall toxicity levels in a flavour or concentration-dependent manner. In fact, we demonstrate that the toxicity of e-cigarette aerosols in vitro derived from all the analysed flavour variants were > 95% reduced when compared to cigarette smoke toxicity."
**Citation: Bishop E, East N, Miazzi F, Fiebelkorn S, Breheny D, Gaca M, Thorne D. A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro. Toxicol Lett. 2023 May 1;380:1-11. doi: 10.1016/j.toxlet.2023.03.006. Epub 2023 Mar 17. PMID: 36935081.

===2022: [https://pubmed.ncbi.nlm.nih.gov/36250607/ Associations between e-cigarette use and e-cigarette flavors with cigarette smoking quit attempts and quit success: Evidence from a US large, nationally representative 2018-2019 survey]===
*E-cigarette use is positively associated with both making a quit attempt and quit success, and those using flavored e-cigarettes are more likely to successfully quit smoking, with no statistically significant differences between the use of menthol or mint-flavored e-cigarettes versus the use of other nontobacco flavored products.
**Citation: Mok Y, Jeon J, Levy DT, Meza R. Associations Between E-cigarette Use and E-cigarette Flavors With Cigarette Smoking Quit Attempts and Quit Success: Evidence From a U.S. Large, Nationally Representative 2018-2019 Survey. Nicotine Tob Res. 2023 Feb 9;25(3):541-552. doi: 10.1093/ntr/ntac241. PMID: 36250607; PMCID: PMC9910159.

===2022: [https://tobaccocontrol.bmj.com/content/31/e1/e10 Association of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USA]===
*Non-tobacco flavours, daily vaping and modifiable e-cigarette devices may help some smokers abstain from cigarette smoking via transitioning to exclusive e-cigarette use, but are also associated with ongoing exclusive e-cigarette use.
**Citation: Harlow AF, Fetterman JL, Ross CS, et alAssociation of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USATobacco Control 2022;31:e10-e17.

===2020: [https://pubmed.ncbi.nlm.nih.gov/32881666/ Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study]=== 


*Our results have shown that flavors considerably enhance antibacterial activity.
*This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.
*Citation: Virginia Fuochi, Massimo Caruso , Rosalia Emma, Aldo Stivala, Riccardo Polosa, Alfio Distefano and Pio Maria Furneri *, “Investigation on the Antibacterial Activity of Electronic Cigarette Liquids (ECLs): A Proof of Concept Study”, Current Pharmaceutical Biotechnology (2020) 21: 1. doi:10.2174/1389201021666200903121624

===2019: [https://www.cmaj.ca/content/re-vape-related-popcorn-lung-debunked-years-ago RE: Vape related "Popcorn Lung" debunked years ago]=== 


*There is 750x more diacetyl in a pack of cigarettes than there is in a days worth of vaping nicotine fluid, and to date we have no confirmation that smokers are getting popcorn lung.

=== 2015 [http://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking] ===
*There's just one minor fact that is omitted completely in the article, as well as in all the media coverage.
*That fact: All conventional cigarettes produce tobacco smoke that contains diacetyl, and the levels of diacetyl in cigarettes are a lot higher than those produced by e-cigarettes.

===2019: [https://www.sciencedirect.com/science/article/pii/S0887233318307768?via%3Dihub High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate]=== 


*Our results clearly show a lower toxicity of e-liquids, including flavoured e-liquids, when compared to [[Special:MyLanguage/Abbreviations|CSC]] (cigarette smoke condensate). Typically, more than 100 times higher concentrations of [[Special:MyLanguage/Abbreviations|CFs]] (commercial flavoured e-liquids) are required to elicit the same response as those observed for 3R4F CSC in specific endpoints.
*Flavours play a critical role in attracting, and retaining smokers to e-cigarettes.
*[https://sci-hub.st/10.1016/j.tiv.2019.03.018 PDF Version]
*Citation: Lukasz Czekala, Liam Simms, Matthew Stevenson, Edgar Trelles-Sticken, Paul Walker, Tanvir Walele, High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate, Toxicology in Vitro, Volume 58, 2019, Pages 86-96, ISSN 0887-2333, doi:10.1016/j.tiv.2019.03.018.

===2019: [https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-019-0318-2?optIn=false Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study]=== 


*The vast majority of flavouring (flavoring) compounds in e-cigarette liquids as reported in a recent study were present at levels far lower than needed to classify them as toxic.
*[https://harmreductionjournal.biomedcentral.com/track/pdf/10.1186/s12954-019-0318-2.pdf PDF Version]
*Farsalinos, K., Lagoumintzis, G. Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study. Harm Reduct J 16, 48 (2019). doi: 10.1186/s12954-019-0318-2

===2019: [https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0222152&fbclid=IwAR1Rqtl6D0eLtqU0-pqJ5vlSlLK2xlJk8rs0djo90oeUAwIdX9IgmYgByZY Effects of flavoring compounds used in electronic cigarette refill liquids on endothelial and vascular function]=== 


*Our data indicate that flavorings typically present in e-cig refill liquids do not cause endothelial dysfunction that would result in impaired vasodilation upon acute exposure. In contrast, most of the tested compounds caused endothelium-independent vasorelaxation, albeit at fairly high concentrations that appear to exceed by far the plasma concentrations expected to occur upon vaping flavored liquids.
*[https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0222152/1/pone.0222152.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210106%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210106T115250Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 PDF Version]
*Citation: Wölkart G, Kollau A, Stessel H, Russwurm M, Koesling D, Schrammel A, et al. (2019) Effects of flavoring compounds used in electronic cigarette refill liquids on endothelial and vascular function. PLoS ONE 14(9): e0222152. https://doi.org/10.1371/journal.pone.0222152

===2018: [https://reason.org/wp-content/uploads/public-health-case-e-cigarette-flavors.pdf A QUESTION OF TASTE: THE PUBLIC HEALTH CASE FOR E-CIGARETTE FLAVORS]=== 


*The available evidence on flavored e-cigarettes suggests that flavors in and of themselves are not especially appealing to non-smoking adults or adolescents. There is, however, a substantial and growing literature on how and why these products appeal to smoking adults and their potential to help consumers switch from smoking to less-harmful vaping.
*'''Any policy that harms the exclusive makers of reduced-risk products such as e-cigarettes more than the makers of traditional cigarettes is not in the interests of public health. '''
*Report Author (55 pages): Guy Bentley

===2018: [http://www.ecigarette-research.org/research/index.php/research/2018/262-flavors Paper: E-cigarette flavors and aldehyde emissions: another failure to verify findings from a previous study]=== 


**Our results were revealing in identifying a very small contribution of flavorings on aldehyde emissions. In fact, '''aldehyde levels were so low that consumption of 5 grams e-liquid per day would expose vapers to less formaldehyde and acetaldehyde than just staying at home and breathing air'''. For acrolein, exposure was orders of magnitude lower compared to NIOSH-defined recommended safety limits. To give you an idea of the differences in results, the authors of the original study found up to 7000 ug/g formaldehyde, while we found a maximum of 62 ug/g.
*2017: Study: [https://www.sciencedirect.com/science/article/abs/pii/S0278691518301339?via%3Dihub Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?]
**In conclusion, we confirmed that flavouring compounds can contribute to aldehyde emissions from ECs, but such contribution, detected in only 3 liquids and two flavours herein, was minimal. (flavor, flavors, flavoring, flavorings)
**[https://sci-hub.se/10.1016/j.fct.2018.02.059# PDF Version]
**Citation: Farsalinos, K. E., & Voudris, V. (2018). Do flavouring compounds contribute to aldehyde emissions in e-cigarettes? Food and Chemical Toxicology, 115, 212–217. doi:10.1016/j.fct.2018.02.059
*2017: Follow Up: [https://pubs.acs.org/doi/10.1021/acs.est.6b06030 Comment on “Flavoring Compounds Dominate Toxic Aldehyde Production during E Cigarette Vaping”]
**We would like to point out that the finding is in a stark contrast to previous results.
**The high levels only happen under dry puff conditions, something avoided by vapers as it is very unpleasant.

===2017: [https://www.cdc.gov/niosh/hhe/reports/pdfs/2015-0107-3279.pdf?fbclid=IwAR37EOr5p5EwptMhuyrIwEDkfi4qbMh0nRwu6yz2VkY0Um-q138f3LfK64Y Evaluation of Chemical Exposures at a Vape Shop]=== 


*We collected air samples for flavoring chemicals (diacetyl, 2,3-pentanedione, 2,3-hexanedione, acetaldehyde, and acetoin), nicotine, formaldehyde, and propylene glycol.
*Concentrations of vaping-related chemicals in our air samples were below occupational exposure limits.
*Citation: NIOSH 2017. Evaluation of chemical exposures at a vape shop. By Zwack LM, Stefaniak AB, LeBouf RF. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Hazard Evaluation Report 2015-0107-3279

===2016: [https://tobaccocontrol.bmj.com/content/25/Suppl_2/ii67 Cigarette smoking and electronic cigarette vaping patterns as a function of e-cigarette flavourings]=== 


*The findings suggest that adoption of e-cigarettes in smokers may influence smoking rates of people who smoke.
*'''E-cigarette vaping rates are influenced by flavorings by people transitioning from smoking'''.
*These findings have implications for the utility of e-cigarettes as a nicotine replacement device and for the regulation of e-cigarettes for harm reduction.
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/25/Suppl_2/ii67.full.pdf PDF Version]
*Citation: Litt MD, Duffy V, Oncken C. Cigarette smoking and electronic cigarette vaping patterns as a function of e-cigarette flavourings, Tobacco Control 2016;25:ii67-ii72.

===2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/234-bo Medical journal misrepresents a case of hypersensitivity pneumonitis as popcorn lung disease caused by e-cigarette]=== 


*It was shocking to see a public statement reporting a case of popcorn lung disease in a patient using e-cigarettes. The title of the public release is: “Case report finds 'popcorn lung' in patient using e-cigarettes. Report points to possibility of diacetyl, a flavoring agent in e-cigarettes, to bronchiolitis obliterans syndrome”
*The case report is NOT about popcorn lung disease. The article then goes on to explain why it can’t be popcorn lung.

===2015: [https://www.sciencedirect.com/science/article/pii/S0273230015001245?via%3Dihub An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids]=== 


*In vitro and Animal
*Individual flavours or groups of flavours were added to the tobacco rod and the resultant smoke was analysed for priority smoke constituents and tested in several in vitro tests as well as 90-day rat inhalation studies. In general, addition of the flavours had no effect on, or reduced the levels of most of the measured smoke constituents.”
*[https://sci-hub.se/10.1016/j.yrtph.2015.05.018 PDF Version]
*Citation: S. Costigan, C. Meredith, An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids, Regulatory Toxicology and Pharmacology, Volume 72, Issue 2, 2015, Pages 361-369, ISSN 0273-2300, doi: 10.1016/j.yrtph.2015.05.018..

===2013: [https://www.mdpi.com/1660-4601/10/10/5146/htm Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour (Vapor) Extract on Cultured Myocardial Cells]=== 


*Smoking is an important risk factor for cardiovascular disease and cigarette smoke (CS) has well-established cytotoxic effects on myocardial cells. The purpose of this study was to evaluate the cytotoxic potential of the vapour of 20 EC (e-cigarette) liquid samples and a “base” liquid sample (50% glycerol and 50% propylene glycol, with no nicotine or flavourings) on cultured myocardial cells. Included were 4 samples produced by using cured tobacco leaves in order to extract the tobacco flavour. Methods: Cytotoxicity was tested according to the ISO 10993-5 standard.
*In conclusion, from 20 commercially-available EC liquids that were tested in vapour form, four were found to be cytotoxic on cultured cardiomyoblasts. Cytotoxicity was mainly observed in most (but not all) samples produced by using tobacco leaves, while one sample using food-approved flavoring was marginally cytotoxic. EC vapour production by using higher-voltage devices caused a decrease in cell survival. Overall, EC vapour extracts showed significantly higher cell viability compared to CS extract, based on a realistic-use rather than a standardized comparative level of exposure. This supports the concept that ECs may be useful as tobacco harm reduction products.
*[https://sci-hub.do/10.3390/ijerph10105146 PDF Version]
*Citation: Farsalinos, K., Romagna, G., Allifranchini, E., Ripamonti, E., Bocchietto, E., Todeschi, S., … Voudris, V. (2013). Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour Extract on Cultured Myocardial Cells. International Journal of Environmental Research and Public Health, 10(10), 5146–5162. doi:10.3390/ijerph10105146

=Regulations or Unintended Consequences= 

===2024: [https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-024-01003-z Exploring the opinions and potential impact of unflavoured e-liquid on smoking cessation among people who smoke and smoking relapse among people who previously smoked and now use e-cigarettes: findings from a UK-based mixed methods study]===
*"The findings highlight that people who smoke and vape could be impacted by flavour restrictions in a range of ways, some of which could have a potential adverse impact on harm reduction efforts in the UK (e.g., by making smoking more appealing than vaping)."
**Citation: Khouja, J.N., Dyer, M.L., Havill, M.A. et al. Exploring the opinions and potential impact of unflavoured e-liquid on smoking cessation among people who smoke and smoking relapse among people who previously smoked and now use e-cigarettes: findings from a UK-based mixed methods study. Harm Reduct J 21, 90 (2024). https://doi.org/10.1186/s12954-024-01003-z

===2024: [https://www.nber.org/papers/w32534 Comprehensive E-cigarette Flavor Bans and Tobacco Use among Youth and Adults]===
*"The vast majority of youth e-cigarette users consume flavored e-cigarettes, raising concerns from public health advocates that flavors may drive youth initiation into and continued use of e-cigarettes...Our findings suggest that statewide comprehensive flavor bans may have generated an unintended consequence by encouraging substitution towards traditional smoking in some populations."
**Citation: Comprehensive E-cigarette Flavor Bans and Tobacco Use among Youth and Adults, Henry Saffer, Selen Ozdogan, Michael Grossman, Daniel L. Dench, and Dhaval M. Dave, NBER Working Paper No. 32534, June 2024, JEL No. H07,I12,I18,J13

===2024: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntae151/7697906?login=false The Impact of New Jersey’s 2020 E-cigarette Flavor Ban on E-cigarette, Cigarette, and Cigar Sales in New Jersey]===
*"Flavored e-cigarette sales were declining prior to the ban but the pace of the decline accelerated following federal and state restrictions on flavored e-cigarette sales, then slowed by the second half of 2020, with a brief period of increased cigarette and cigar sales immediately following the ban."
**Citation: Mary Hrywna, Arjun Teotia, Erin Miller Lo, Daniel P Giovenco, Cristine D Delnevo, The Impact of New Jersey’s 2020 E-cigarette Flavor Ban on E-cigarette, Cigarette, and Cigar Sales in New Jersey, Nicotine & Tobacco Research, 2024;, ntae151, https://doi.org/10.1093/ntr/ntae151

===2023: [https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4586701 E-cigarette Flavor Restrictions’ Effects on Tobacco Product Sales]===
*"Over 375 US localities and 7 states have adopted permanent restrictions on sales of flavored electronic nicotine delivery systems (“ENDS”). These policies’ effects on combustible cigarette use, a more harmful habit, remain unclear. Matching new flavor policy data to retail sales data, we find a tradeoff of 12 additional cigarettes for every 1 less 0.7 mL ENDS pod sold due to ENDS flavor restrictions. Further, cigarette sales increase even among brands disproportionately used by underage youth. Thus, any public health benefits of reducing ENDS sales via flavor restrictions may be offset by public health costs from increased cigarette sales."
**Citation: Friedman, Abigail and Liber, Alex C. and Crippen, Alyssa and Pesko, Michael, E-cigarette Flavor Restrictions’ Effects on Tobacco Product Sales (September 26, 2023). Available at SSRN: https://ssrn.com/abstract=4586701 or http://dx.doi.org/10.2139/ssrn.4586701

===2023: [https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntad258/7492743 Responses to real-world and hypothetical e-cigarette flavor bans among US young adults who use flavored e-cigarettes]===
*"Young adults who vape flavored e-cigarettes have mixed responses to e-cigarette flavor bans. Under both real-world and hypothetical e-cigarette flavor bans, most who use flavored e-cigarettes continue vaping. Under a real-world ban, the second most common response among those who exclusively vape is to switch to smoking; under a hypothetical federal ban, it is to quit all tobacco."
*Citation: Jamie Tam, Evelyn Jimenez-Mendoza, John Buckell, Jody Sindelar, Rafael Meza, Responses to Real-World and Hypothetical E-Cigarette Flavor Bans Among US Young Adults Who Use Flavored E-Cigarettes, Nicotine & Tobacco Research, 2023;, ntad258, https://doi.org/10.1093/ntr/ntad258

===2022: [https://www.sciencedirect.com/science/article/abs/pii/S0091743522001116 Effect of flavored E-cigarette bans in the United States: What does the evidence show?]===
*However, in this paper, we propose an evidence-based version of this model based on several years' worth of longitudinal and econometric research, which suggests that youth e-cigarette use has instead worked to replace a culture of youth smoking. From this analysis, we propose a re-evaluation of current policies surrounding e-cigarette sales so that declines in e-cigarette use will not come at the cost of increasing cigarette use among youth and adults.
**Citation: Siegel M, Katchmar A. Effect of flavored E-cigarette bans in the United States: What does the evidence show? Prev Med. 2022 Dec;165(Pt B):107063. doi: 10.1016/j.ypmed.2022.107063. Epub 2022 Apr 20. PMID: 35452711.

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287473/ Impact of existing and potential e-cigarette flavor restrictions on e-cigarette use among young adult e-cigarette users in 6 US metropolitan areas]===
*Results from this study highlight heterogeneity in young adult e-cigarette users’ reactions to existing flavored e-cigarette sales restrictions and hypothetical restrictions. Some reduced e-cigarette use, but many reported intentions to continue e-cigarette use, by using tank-based e-cigarettes, available flavors, or flavors accessed through alternative sources. More concerning, some switched to cigarettes. Similarly, in response to future restrictions of all flavored e-liquids, young adult e-cigarette users largely indicated that they would either quit vaping – the ideal scenario – or switch to cigarettes – the least desirable scenario. Another major concern highlighted was access to flavored e-cigarettes despite restrictions (e.g., online, across state lines). Collectively, findings suggest that implications of flavored e-cigarette sales restrictions are complex, with the potential for both reductions in e-cigarette use and unintended consequences among young adults, including continued use of flavored e-cigarettes or switching to cigarettes, and retail and consumer circumvention of restrictions.
**Citation: Romm KF, Henriksen L, Huang J, Le D, Clausen M, Duan Z, Fuss C, Bennett B, Berg CJ. Impact of existing and potential e-cigarette flavor restrictions on e-cigarette use among young adult e-cigarette users in 6 US metropolitan areas. Prev Med Rep. 2022 Jul 9;28:101901. doi: 10.1016/j.pmedr.2022.101901. PMID: 35855926; PMCID: PMC9287473.

===2022: [https://academic.oup.com/ntr/article/24/9/1332/6550857 The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review]===
*"E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers."
**Citation: Mari S Gades, Aleksandra Alcheva, Amy L Riegelman, Dorothy K Hatsukami, The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review, Nicotine & Tobacco Research, Volume 24, Issue 9, September 2022, Pages 1332–1343, https://doi.org/10.1093/ntr/ntac073
***Acknowledgment: This work was supported by the National Institute of Drug Abuse (T32 DA007097 and R36 DA050000 to MSG); and the National Institutes of Health (P01 CA217806 to DKH).

===2022: PREPRINT: [https://www.medrxiv.org/content/10.1101/2022.11.14.22282288v1 A decision aid for policymakers to estimate the impact of e-cigarette flavour restrictions on population smoking and e-cigarette use prevalence among youth versus smoking prevalence among adults]===
*"We demonstrated the value of this decision aid using data from various sources to estimate the impact of a flavour ban in three populations: the general UK population, low-socioeconomic position UK population, and the general US population. All three examples suggested a negative net population impact of a ban. These reports were then presented to the all-party parliamentary group for vaping."
*[https://www.medrxiv.org/content/10.1101/2022.11.14.22282288v1.full.pdf PDF of full paper]
**Citation: A decision aid for policymakers to estimate the impact of e-cigarette flavour restrictions on population smoking and e-cigarette use prevalence among youth versus smoking prevalence among adults Mark J Gibson, Marcus R Munafò, Angela S. Attwood, Martin J. Dockrell, Michelle A. Havill, Jasmine N Khouja medRxiv 2022.11.14.22282288; doi: https://doi.org/10.1101/2022.11.14.22282288

===2022: [https://pubmed.ncbi.nlm.nih.gov/36328469/ Removal of mango-flavoured Juul pods created opportunity for adulterated mango Juul-compatible pods with altered chemical constituents]===
*"Adulterated Juul-compatible products may expose e-cigarette consumers to more chemical constituents at higher concentrations than previously found in the original product, despite similarity in product design."
**Citation: Dell LG, Page MK, Leigh NJ, Goniewicz ML. Removal of mango-flavoured Juul pods created opportunity for adulterated mango Juul-compatible pods with altered chemical constituents. Tob Control. 2022 Nov;31(Suppl 3):s230-s233. doi: 10.1136/tc-2022-057476. PMID: 36328469; PMCID: PMC9664127.

===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145156/ A Difference-in-Differences Analysis of Youth Smoking and a Ban on Sales of Flavored Tobacco Products in San Francisco, California]===
*San Francisco’s ban on flavored tobacco product sales was associated with increased smoking among minor high school students relative to other school districts. While the policy applied to all tobacco products, its outcome was likely greater for youths who vaped than those who smoked due to higher rates of flavored tobacco use among those who vaped. This raises concerns that reducing access to flavored electronic nicotine delivery systems may motivate youths who would otherwise vape to substitute smoking. Indeed, analyses of how minimum legal sales ages for electronic nicotine delivery systems are associated with youth smoking also suggest such substitution.
*Citation: Friedman AS. A Difference-in-Differences Analysis of Youth Smoking and a Ban on Sales of Flavored Tobacco Products in San Francisco, California. JAMA Pediatr. 2021;175(8):863-865. doi:10.1001/jamapediatrics.2021.0922

===2021: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntab154/6332852?redirectedFrom=fulltext Reactions to sales restrictions on flavored vape products or all vape products among young adults in the US]=== 


*Young adult e-cigarette users indicate low support for e-cigarette sales restrictions (both for flavored products and complete restrictions). Moreover, if vape product sales were restricted to tobacco flavors, 39.1% of users reported being likely to continue using e-cigarettes but 33.2% were likely to switch to cigarettes. If vape product sales were entirely restricted, e-cigarette users were equally likely to switch to cigarettes versus not (~40%).
*Free version of full study or PDF not available
*Citation: Heather Posner, MPH, Katelyn F Romm, PhD, Lisa Henriksen, PhD, Debra Bernat, PhD, Carla J Berg, PhD, MBA, Reactions to Sales Restrictions on Flavored Vape Products or All Vape Products Among Young Adults in the United States, Nicotine & Tobacco Research, 2021;, ntab154, doi: 10.1093/ntr/ntab154

===2021: [https://f1000research.com/articles/10-619/v1 Vaping liquid flavour preferences, oral nicotine pouch and cannabis use: A survey of participants in the 2019 Oceania Vape Expo (version 1; peer review: awaiting peer review)]===
*In the event of a ban on other flavours, 20% of the NZ residents said they would probably go back to smoking (see Table 3). A majority (57%) indicated they intended to circumvent the ban, by mixing their own liquids and/or buying from overseas or the black market. Only 29% indicated they would change their vaping consumption to comply with the ban, as is typically implicitly assumed will happen. Nine percent would try to stop vaping and 35% would buy only the legal products (which includes the 18% who were already buying only products that would not be banned).
*[https://f1000research.com/articles/10-619/v1/pdf?article_uuid=853423ae-6086-4c13-a7bc-87b28d81a4a6 PDF Version]
*Citation: Glover M, Phillips CV, Selket K and Jeffares Y. Vaping liquid flavour preferences, oral nicotine pouch and cannabis use: A survey of participants in the 2019 Oceania Vape Expo [version 1; peer review: awaiting peer review]. F1000Research 2021, 10:619 doi:10.12688/f1000research.54582.1

===2021: Testimony in Netherlands pertaining to a potential flavour / flavor ban: [https://www.clivebates.com/documents/NLFlavoursResponseJan2021.pdf Regulation of e-cigarette flavours – a response]=== 


*Signed by 24 experts from around the world
*Covers 12 key points

===2021: [https://www.sciencedirect.com/science/article/pii/S0306460321003373 Responses to potential nicotine vaping product flavor restrictions among regular vapers using non-tobacco flavors: Findings from the 2020 ITC Smoking and Vaping Survey in Canada, England and the United States]===
*Conclusion: "At this time, it is not yet clear exactly how NVP flavor bans will play out as they are implemented across national and sub-national jurisdictions. However, by extrapolating from this study, and the other limited studies available, it appears that the outcomes will be mixed and complex. While our study suggests most vapers are opposed to a ban, and some vapers indicated that such a ban would lead to unintended consequences (e.g., taking up cigarette smoking again, or turning to illicit channels), many vapers said that they would be willing to vape available flavors. Thus, it is important for policy makers to weigh the potential for public health consequences, as well as possible benefits."
**Citation: Gravely S, Smith DM, Liber AC, Cummings KM, East KA, Hammond D, Hyland A, O'Connor RJ, Kasza KA, Quah ACK, Loewen R, Martin N, Meng G, Ouimet J, Thompson ME, Boudreau C, McNeill A, Sweanor DT, Fong GT. Responses to potential nicotine vaping product flavor restrictions among regular vapers using non-tobacco flavors: Findings from the 2020 ITC Smoking and Vaping Survey in Canada, England and the United States. Addict Behav. 2022 Feb;125:107152. doi: 10.1016/j.addbeh.2021.107152. Epub 2021 Oct 14. PMID: 34695685; PMCID: PMC9094050.
***Acknowledgment: This study was supported by grants from the US National Cancer Institute (P01 CA200512), the Canadian Institutes of Health Research (FDN-148477), the National Health and Medical Research Council of Australia (APP 1106451). GTF was supported by a Senior Investigator Award from the Ontario Institute for Cancer Research (IA-004) and the Canadian Cancer Society 2020 O. Harold Warwick Prize. AH and RJO are supported by a Tobacco Centers of Regulatory Science US National Cancer Institute grant (U54 CA238110). AL is supported by the Center for the Assessment of Tobacco Regulations (U54CA229974). AM is a National Institute for Health Research (NIHR) Senior Investigator. These funders/supporting agencies had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. Declarations of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. KMC has served as paid expert witness in litigation filed against cigarette manufacturers. GTF and DH have served as expert witnesses on behalf of governments in litigation involving the tobacco industry. AM is a UK National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the authors and not necessarily those of the NIHR, or the UK Department of Health and Social Care.

===2020: [https://sci-hub.st/https://onlinelibrary.wiley.com/doi/10.1111/add.15235# Association of vaping‐related lung injuries with rates of e‐cigarette and cannabis use across US states]=== 


*'''Policymakers should proceed with caution when considering bans on flavored nicotine e‐liquids''': restricting legal sales may push some vapers towards illicit sources, user‐modified e‐liquids (e.g. to add flavoring) or even conventional cigarette use. Given EVALI’s potential lethality and a myriad of work suggesting that conventional cigarette use is probably far more dangerous than vaping nicotine, these outcomes could be disastrous for public health. There is no link between nicotine liquids and EVALI. It appears to have come from illicit cannabis products.
*Link above is to the PDF version
*Citation: Friedman, A. S. (2020). Association of Vaping‐related Lung Injuries with Rates of E‐cigarette and Cannabis Use across US States. Addiction. doi:10.1111/add.15235

===2020: [https://www.sciencedirect.com/science/article/pii/S2352853220300134 The impact of a comprehensive tobacco product flavor ban in San Francisco among young adults]=== 


*Among the 18–24 age group, there was a significant increase in cigarette smoking.
*Cigarette smoking increased among 25–34 years old.
*'''Banning flavors in e-cigarettes can push some e-cigarette users to turn to cigarette smoking''' and could prompt some youth to initiate into smoking instead of e-cigarette use.
*The proportions of e-cigarettes, cigarettes, and cigars obtained over the internet increased after the ban, and the proportions obtained from retailers outside of San Francisco also increased overall.
*[https://sci-hub.st/10.1016/j.abrep.2020.100273 PDF Version]
*Citation: Yang, Y., Lindblom, E. N., Salloum, R. G., & Ward, K. D. (2020). The impact of a comprehensive tobacco product flavor ban in San Francisco among young adults. Addictive Behaviors Reports, 11, 100273. doi:10.1016/j.abrep.2020.100273

===2020: Article: [https://www.realclearpolicy.com/articles/2020/10/01/yale_study_on_lung_disease_forecasts_dire_consequences_for_flavor_bans_579308.html Yale Study on Lung Disease Forecasts Dire Consequences for Flavor Bans]=== 


*A new study from Yale School of Public Health should serve as a warning to e-cigarette opponents and public health officials pushing e-cigarette flavor bans and restrictions around the country.
*By pushing people into the black market for flavored products, they are increasing the risk that we will see another wave of consumers sickened by unregulated, illegal goods.
*Citation: Elizabeth Sheld, Real Clear Policy, October 01, 2020.

===2019: [https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201906-472OC Changes in Flavor Preference in a Cohort of Long-Term Electronic Cigarette Users]=== 


*Our results regarding anticipated reactions to FDA e-cigarette flavor regulation suggest complexities such that the benefits and risks of flavor ban need to be carefully evaluated.
*'''A majority anticipated that they would personally attempt to circumvent potential FDA regulations of e-cigarettes by obtaining e-cigarette flavors from various illicit sources''' (e.g., Internet orders from foreign countries) or even self-making flavors.
*The use of flavoring agents purchased from unregulated sources could lead to additional unanticipated toxicities.
*'''It is also concerning that some established e-cigarette users believed that they would return to cigarette smoking if nontobacco e-cigarette flavors were banned'''. Thus, for adult e-cigarette users who use certain flavors to facilitate smoking cessation or reduction, banning all nontobacco flavors could precipitate relapse to smoking.
*[https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.201906-472OC PDF Version]
*Citation: Ann Am Thorac Soc Vol 17, No 5, pp 573–581, May 2020, Copyright © 2020 by the American Thoracic Society, DOI: 10.1513/AnnalsATS.201906-472OC

===2019: Article: [https://www.detroitnews.com/story/opinion/2019/09/16/opinion-vape-flavor-ban-doesnt-help-kids-hurts-adults/2291817001/ Vape flavor ban doesn't help kids, hurts adults]=== 


*Tobacco users who switch from combustible cigarettes to e-cigarettes experience various improvements in health.
*Using e-cigarettes also helps people quit smoking altogether, with twice the success rate of other quit methods.
*Researchers have yet to demonstrate that an e-cigarette flavor ban will prevent minors from obtaining and experimenting with tobacco products.
*The ban creates a greater opportunity for people — including adolescents — to interact with law enforcement, putting them at increased risk of becoming involved with the criminal justice system.
*Citation: Jesse Kelly & Carrie Wade, September 15, 2019, The Detroit News

===2019: Article: [https://www.wwlp.com/news/state-politics/flavor-ban-will-feed-illegal-tobacco-sales-stores-say/ Flavor ban will feed illegal tobacco sales, stores say]=== 


*A retired federal law enforcement officer cautioned against banning flavors.
*“If this bill passes and we bring in prohibition, we’re going to bring crime into the city,” Marianos, who is now an adjunct faculty member at Georgetown University, said. “We’re going to replace store owners and manufacturers with people selling out of backpacks, people selling out of cars, and worst of all, people selling directly to the children we’re trying to protect.”
*Citation: Colin Young, November 04, 2019, 22 News WWLP

===2019: Article: [https://www.sun-sentinel.com/opinion/commentary/fl-op-com-minton-e-cigarette-ban-ineffective-dangerous-20190923-svobcmjbdjeptduwlqdx6blcii-story.html E-cigarette flavor ban — ineffective and dangerous]=== 


*Bans don’t work. Bans never work. All bans do is push consumers to make different, usually more risky, choices. In this case, the likely outcome of banning e-liquid flavors people want is that they will seek to obtain them through the black market or simply return to smoking cigarettes. As a result, many more will die of smoking-related diseases or tainted products.
*The wide array of flavors, produced by thousands of vapor companies around the country — most of them small — appear to be critical in persuading smokers to try vaping and preventing e-cigarette users from returning to their deadly combustible cigarette habit.
*As a society, we have found satisfactory ways to address youth access to many adult products, like alcohol and marijuana. Given that e-cigarettes have the potential to save lives, regulators have a responsibility to find a similarly sophisticated solution to the youth vaping problem. Or, they can follow Michigan’s lead and learn the same lesson repeated throughout history: prohibition always causes more problems than it solves.
*Citation: Michelle Minton, September 23, 2019, South Florida Sun Sentinel

===2019: Article: [https://www.kqed.org/science/1950849/vapers-turn-to-home-brew-as-flavored-nicotine-bans-mount Vapers Turn to Home Brew as Flavored Nicotine Bans Mount]=== 


*“Even though I haven’t touched a cigarette in five years, the pull is always there. It’s so easy to go and buy a pack. And I don’t want to do that,” Danielle Jones said. “The only route I can see going forward if there is a ban is to try to create the product myself at home.”
*As more states, cities and even the federal government consider banning flavored nicotine, thousands of do-it-yourself vapers like Jones are flocking to social media groups and websites to learn how to make e-liquids at home.
*“To have people mixing their own e-cigarette liquid is crazy.” said Stanton Glantz, a professor of medicine and the director of the Center for Tobacco Control Research and Education at the University of California-San Francisco.
*Dr. Michael Siegel, a professor of community health sciences at Boston University, worries about the risk of contaminated products as some people use the bans as an opportunity to make their own concoctions cheaply and sell them on the black market. “Who knows what they’re going to put in there?” Siegel said. “This is just what happens when you use prohibition as a regulatory approach.
*Alex Clark, CEO of the Consumer Advocates for Smoke-Free Alternatives Association (CASAA), said he plans to warn the nonprofit’s more than 200,000 members about the dangers of making e-liquid at home. Clark notes that people should not use flavors found in the baking aisle of a grocery store.
*Citation: Jenny Gold, November 12, 2019, Kaiser Health News KQED

===2019: Article: [https://www.theatlantic.com/ideas/archive/2019/10/danger-vaping-bans/600451/ The Vaping Overreaction Politicians who ban flavors should brace for a surge in cigarette smoking and the use of questionable bootleg vaping products.]=== 


*The ethos of vaping is relative risk. E-cigarettes reduce harm, but can’t be called harmless. As a safer alternative than smoking for people addicted to nicotine, they are analogous to prescribing methadone for people addicted to opioids, a strategy called harm reduction. Other kinds of harm reduction, such as giving clean needles to injection-drug users and distributing condoms, pre-exposure prophylactic medication, and safe-sex information for populations at risk for HIV/AIDS, are widely endorsed by the public-health establishment.
*In light of history, public-health advocates’ skepticism about e-cigarettes, at least when they first appeared, was understandable. But genuine advances really can occur, and the evidence suggests that the shift from smoking to vaping should be celebrated, not decried.
*Claims that nicotine alone leads to brain damage in youth have limited empirical support; most of the relevant literature involves studies of teens exposed to the substance via smoking. I mention this not to dismiss the problem of teen vaping—the FDA and other agencies are rightly trying to curb teen access—but merely to warn against rash, misdirected responses that will prevent today’s smokers from quitting.
*Unfortunately, the misconceptions surrounding vaping may be too well entrenched. A Kaiser poll conducted this month revealed that 49 percent of respondents support banning all e-cigarettes, not just flavored ones. That would be a deadly mistake. “If we lose this opportunity,” David S. Abrams, a professor at the New York University College of Global Public Health, told CBS Morning News last month, “we will have blown the single biggest public-health opportunity ever to get rid of cigarettes and replace them with a much safer form of nicotine for everybody.” With 35 million Americans still smoking, the stakes are high.

===2019: [https://www.tandfonline.com/doi/abs/10.1080/10826084.2019.1626435?journalCode=isum20 Young adult dual combusted cigarette and e-cigarette users’ anticipated responses to hypothetical e-cigarette market restrictions]=== 


*Hypothetical regulations resulted in reported intentions to reduce EC (e-cigarette) use and increase CC (combustible cigarette) use; the greatest impact was found for restrictions regarding e-liquid nicotine content, followed by flavor
*This work provides preliminary evidence that restrictive regulations regarding key EC characteristics may increase intentions to increase CC use among young adult dual EC and CC users.
*[https://sci-hub.se/10.1080/10826084.2019.1626435 PDF Version]
*Citation:: Lauren R. Pacek, Olga Rass, Maggie M. Sweitzer, Jason A. Oliver & F. Joseph McClernon (2019): Young adult dual combusted cigarette and e-cigarette users’ anticipated responses to hypothetical e-cigarette market restrictions, Substance Use & Misuse, DOI:10.1080/10826084.2019.1626435

===2018: [https://www.regulations.gov/document?D=FDA-2017-N-6565-22941 Patterns of flavored e-cigarette use among adults vapers in the United States: an internet survey]=== 


*Survey results submitted to the FDA
*In conclusion, this cross-sectional study of a very large sample of adult US e-cigarette users, most of which were former smokers, identified the importance of non-tobacco flavors in e-cigarette use initiation and sustained use, and their contribution to smoking cessation and relapse prevention. *'''This information should be considered by regulators in order to avoid unintentional adverse effects of over-restrictive regulation on e-cigarette flavors'''.
*[https://www.regulations.gov/contentStreamer?documentId=FDA-2017-N-6565-22941&attachmentNumber=1&contentType=pdf PDF Version]
*Citation: Konstantinos Farsalinos, MD, MPH, Christopher Russell, PhD, George Lagoumintzis, PhD, Konstantinos Poulas, Submitted to: Docket No. FDA-2017 N-6565 for “Regulation of Flavors in Tobacco Products.”

===2018: [https://tobaccocontrol.bmj.com/content/28/2/168 Should flavours be banned in cigarettes and e-cigarettes? Evidence on adult smokers and recent quitters from a discrete choice experiment]=== 


*A ban on flavoured e-cigarettes would likely increase the choice of cigarettes in smokers, the more harmful way of obtaining nicotine.
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/28/2/168.full.pdf PDF Version]
*Citation:Buckell J, Marti J, Sindelar JLShould flavours be banned in cigarettes and e-cigarettes? Evidence on adult smokers and recent quitters from a discrete choice experimentTobacco Control 2019;28:168-175.

=Relapse Prevention or Long Term Abstinence= 

===2020: [https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-020-00418-8 Reported patterns of vaping to support long-term abstinence from smoking: a cross-sectional survey of a convenience sample of vapers]=== 


*Qualitative research suggests e-cigarettes can meet many of the needs of ex-smokers by substituting physical, psychological, social, cultural and identity-related aspects of tobacco addiction.
*According to a time-series analysis of data from the Smoking Toolkit study, in which repeated cross-sectional surveys are conducted with a representative sample of households in England, increasing prevalence of e-cigarette use in current smokers was predictive of higher success rates of quit attempts.
*Most participants were self-reported long-term abstinent smokers (86.3%).
*Those who start on a low self-reported nicotine e-liquid concentration (strength) will be more likely to relapse to tobacco smoking than those starting on a higher nicotine e-liquid, after controlling for cigarettes per day (CPD) before cessation.
*Results suggest a change in flavor choices over the course of vaping initiation and uptake. There was a reduction in the proportion of people using a tobacco flavor, and increase in the proportion using a fruit/sweet/food flavor, from initial to current flavor choice
*According to the 2017 ASH-A survey, '''among current users, fruit flavors were the most popular'''.
*[https://sci-hub.st/10.1186/s12954-020-00418-8# PDF Version]
*Citation: Gentry, S.V., Ward, E., Dawkins, L. et al. Reported patterns of vaping to support long-term abstinence from smoking: a cross-sectional survey of a convenience sample of vapers. Harm Reduct J 17, 70 (2020). doi:10.1186/s12954-020-00418-8

===2019: Article: [https://www.insidesources.com/e-cigarette-flavor-bans-will-drive-more-people-back-to-smoking/ E-Cigarette Flavor Bans Will Drive More People Back to Smoking]=== 


*These laws will result in thousands of ex-smokers returning to cigarette smoking because the e-cigarettes they rely upon are taken off the shelves, while tobacco cigarettes remain. The absurdity of these proposals is that they restrict the sale of e-cigarettes more severely than the sale of actual cigarettes, the ones that are killing more than 400,000 Americans each year. Why would regulators want to give a competitive advantage to cigarettes over the much safer alternative?
*By creating barriers to a much healthier product, these laws will simply force former smokers to return to cigarette smoking. Lawmakers are doing a huge favor not for the public’s health, but for Marlboro, which is going to see a windfall in the ex-smoker market as all of its competition from vaping products is eliminated.
*Citation: Michael Siegel, February 19, 2019, Inside Sources

=Smoking Cessation= 

===2021: [https://academic.oup.com/ntr/article-abstract/23/9/1490/6149939 How Does the Use of Flavored Nicotine Vaping Products Relate to Progression Toward Quitting Smoking? Findings From the 2016 and 2018 ITC 4CV Surveys]=== 


*Use of fruit and other sweet flavored e-liquids is positively related to smokers’ transition away from cigarettes.
*Citation: Lin Li, PhD, Ron Borland, PhD, Kenneth Michael Cummings, PhD, Geoffrey T Fong, PhD, Shannon Gravely, PhD, Danielle M Smith, MPH, Maciej L Goniewicz, PhD, Richard J O’Connor, PhD, Mary E Thompson, PhD, Ann McNeill, PhD, How Does the Use of Flavored Nicotine Vaping Products Relate to Progression Toward Quitting Smoking? Findings From the 2016 and 2018 ITC 4CV Surveys, Nicotine & Tobacco Research, Volume 23, Issue 9, September 2021, Pages 1490–1497, doi: 10.1093/ntr/ntab033

===2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275248/ Associations of Flavored e-Cigarette Uptake With Subsequent Smoking Initiation and Cessation]=== 


*'''Adults who began vaping nontobacco-flavored e-cigarettes were more likely to quit smoking than those who vaped tobacco flavors'''.
*Banning flavors altogether may be too blunt an instrument for the current problem (youth use of vapor products).
*[https://sci-hub.st/10.1001/jamanetworkopen.2020.3826# PDF Version]
*Citation: Friedman, A. S., & Xu, S. (2020). Associations of Flavored e-Cigarette Uptake With Subsequent Smoking Initiation and Cessation. JAMA Network Open, 3(6), e203826. doi:10.1001/jamanetworkopen.2020.3826

===2019: [https://www.sciencedirect.com/science/article/abs/pii/S0306460318311821 The role of flavors in vaping initiation and satisfaction among U.S. adults]=== 


*Most common reasons for vaping initiation were as an alternative to cigarettes (43.7%) and because respondents viewed e-cigarettes as less harmful than other tobacco products (31.2%). Flavor was the third most commonly reported reason.
*'''Satisfaction among those who bought flavored e-liquid was higher than those who did not buy flavored e-liquid'''.
*[https://sci-hub.st/10.1016/j.addbeh.2019.106077# PDF Version]
*Citation: Landry, R. L., Groom, A. L., Vu, T.-H. T., Stokes, A. C., Berry, K. M., Kesh, A., … Payne, T. J. (2019). The role of flavors in vaping initiation and satisfaction among U.S. adults. Addictive Behaviors, 106077. doi:10.1016/j.addbeh.2019.106077

===2019: [https://pubmed.ncbi.nlm.nih.gov/31477072/ Vaping patterns, nicotine dependence and reasons for vaping among American Indian dual users of cigarettes and electronic cigarettes]=== 


*The ten-item Penn State Dependence Index (PSDI) suggested greater dependence on smoking than vaping
*'''The most common reasons for vaping were to reduce smoking (79%)''', enjoyment of flavors (78%), and ability to vape where smoking is not allowed (73%). Perceptions of less harm to others (69%) or to self were the next most common (65%). Fewer than half used ECs to reduce stress, for affordability, or because others used them.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721166/pdf/12889_2019_Article_7523.pdf PDF Version]
*Citation: Rhoades DA, Comiford AL, Dvorak JD, Ding K, Hopkins M, Spicer P, Wagener TL, Doescher MP. Vaping patterns, nicotine dependence and reasons for vaping among American Indian dual users of cigarettes and electronic cigarettes. BMC Public Health. 2019 Sep 2;19(1):1211. doi: 10.1186/s12889-019-7523-5. PMID: 31477072; PMCID: PMC6721166.

===2019: [https://www.youtube.com/watch?v=WqTdqLZQUCo Video: Can Flavors Help People Who Smoke Quit Smoking?]=== 


*Minnesota Smoke-Free Alliance
*Do flavors help adults quit smoking? Is there "right" flavored products and "wrong" flavored products? Do we have the right to tell people they have to quit smoking using a method we approve of? (English)

===2019: Article: [https://docs.google.com/document/d/18yNyRhNe0liQ_uP3tSEcaLV9JB-gLyMEnCuE8aLBtPc/edit?usp=sharing Flavors make vaping more palatable, help cigarette smokers kick the habit]=== 


*Flavored e-cigarettes were not invented by “Big Tobacco,” nor are they an unscrupulous marketing plot from the thousands of small, independently owned vape companies in the United States to addict kids. Non-tobacco vape flavors are a user innovation.
*Fruit, candy, bakery, mint, and beverage flavors were introduced to vaping in 2008 by pioneering users of the technology who were desperate to use e-cigarettes to replace smoking.
*Flavors like cotton candy, bubble gum, and the many other examples opponents claim are obviously targeted to youth are in fact flavors someone trying to quit smoking wanted to vape and mixed themselves. These innovations in home-mixing resulted in the commercial market about to be banned today.
*The preponderance of evidence indicates that non-tobacco flavors, including fruit, dessert, and candy, are essential to vaping as an effective way to quit smoking and avoid relapse.
*Citation: Amelia Howard, September 21, 2019, Pro/Con: As vaping-related illnesses rise, should flavored e-cigarettes be banned?, The Philadelphia Enquirer

===2019: Article: [https://web.archive.org/web/20191129093506/https://www.chieftain.com/opinion/20191128/banning-flavored-e-cigarettes-has-consequences Banning flavored e-cigarettes has consequences]=== 


*Instead of clamping down on teen vaping or socking it to Juul, a total vape flavor ban would shut down more than 14,000 small businesses and put at least 166,000 people out of work, while denying millions of Americans access to the tools they used to quit smoking.
*E-cigarettes are known to be at least 95 percent safer than combustible cigarettes. If every smoker in America switched to vaping, as many as 6.6 million lives could be saved over the next decade.
*Additionally, a study published in the New England Journal of Medicine found e-cigarettes to be almost twice as effective as traditional nicotine replacement therapies at helping smokers quit.
*The consequences of banning flavors are as obvious as they are tragic. Analyzing the potential effects of different tobacco flavor bans, researchers at the Yale School of Public Health concluded that banning e-cigarette flavors would result in more smoking.
*Citation: Guy Bentley, November 28, 2019, The Pueblo Chieftain

===2018: [https://academic.oup.com/ntr/article-abstract/20/8/977/4061315?redirectedFrom=fulltext Advice From Former-Smoking E-Cigarette Users to Current Smokers on How to Use E-Cigarettes as Part of an Attempt to Quit Smoking]=== 


*This study describes the advice that former-smokers who used e-cigarettes to quit smoking would offer to smokers who are considering using an e-cigarette to support an attempt to quit smoking. '''Vapers advised smokers to find the right combination of device, flavors and nicotine strength''', continue to smoke and vape for a while if they wished, not be deterred by past failed attempts to quit smoking, and expect health to improve after they have switched to vaping. Encouraging smokers to interact with vaping peers in vape shops and in online vaping-dedicated discussion forums may help significantly more smokers switch to vaping.
*[https://sci-hub.do/10.1093/ntr/ntx176# PDF Version]
*Citation: Christopher Russell, PhD, Tiffany Dickson, MSc, Neil McKeganey, PhD, Advice From Former-Smoking E-Cigarette Users to Current Smokers on How to Use E-Cigarettes as Part of an Attempt to Quit Smoking, Nicotine & Tobacco Research, Volume 20, Issue 8, August 2018, Pages 977–984, doi: 10.1093/ntr/ntx176

===2018: [https://bmjopen.bmj.com/content/8/3/e018329.full Motivation and main flavour of use, use with nicotine and dual use of electronic cigarettes in Barcelona, Spain: a cross-sectional study ]===
*The most prevalent motivation for using e-cigarettes was to reduce tobacco smoking 48%, followed by quitting smoking 39.2%, and to use e-cigarettes in places where tobacco smoking was prohibited 10.2%.
*Citation: Bunch K, Fu M, Ballbè M, et alMotivation and main flavour of use, use with nicotine and dual use of electronic cigarettes in Barcelona, Spain: a cross-sectional studyBMJ Open 2018;8:e018329. doi: 10.1136/bmjopen-2017-018329

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800112/ Differences between Dual Users and Switchers Center around Vaping Behavior and Its Experiences Rather than Beliefs and Attitudes]=== 


*To the extent that dual users substantially lower the number of cigarettes, they will reduce health risks from smoking. However, from a medical point of view, exclusive vaping is preferable to dual use;
*Differences between dual users and switchers center around variables proximal to the vaping behavior and its experienced effects rather than hinging on more general vaping-related beliefs and attitudes.
*After e-cig initiation, dual users decreased tobacco consumption by 82% and were low-to-moderately cigarette dependent.
*'''The two groups (dual users and switchers) reported mostly using a flavor other than tobacco'''.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800112/pdf/ijerph-15-00012.pdf PDF Version]
*Citation: Adriaens K, Van Gucht D, Baeyens F. Differences between Dual Users and Switchers Center around Vaping Behavior and Its Experiences Rather than Beliefs and Attitudes. Int J Environ Res Public Health. 2017 Dec 23;15(1):12. doi: 10.3390/ijerph15010012. PMID: 29295483; PMCID: PMC5800112.

===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808473/ Preferred Flavors and Reasons for E-cigarette Use and Discontinued Use Among Never, Current, and Former Smokers]=== 


*Never users had significantly lower prevalence of use of alcohol, marijuana, and other tobacco products (take less risks).
*The most commonly reported reasons for e-cigarette use were “they might be less harmful than cigarettes” (77%); “they don’t smell” (77%); “they help people quit smoking” (66%); and “they cost less than other forms of tobacco” (62%); these reasons were more frequently endorsed by former smokers.
*Among current e-cigarette users, the most commonly used flavor was fruit flavors (67%)
*'''Over 90% of former cigarette smokers who were current e-cigarette users reported using e-cigarettes to quit smoking'''.
*Over half of never smokers who are former e-cigarette users said they did not recently use e-cigarettes because they “just don’t think about it”, possibly indicating that addiction did not play a role in their use.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808473/pdf/nihms739529.pdf PDF Version]
*Citation: Berg CJ. Preferred flavors and reasons for e-cigarette use and discontinued use among never, current, and former smokers. Int J Public Health. 2016 Mar;61(2):225-36. doi: 10.1007/s00038-015-0764-x. Epub 2015 Nov 18. PMID: 26582009; PMCID: PMC4808473.

===2013: [https://www.mdpi.com/1660-4601/10/12/7272/htm Impact of Flavour Variability on Electronic Cigarette Use Experience: An Internet Survey]=== 


*4,618 participants were included in the analysis, with 4,515 reporting current smoking status (current vs. former smokers).
*More than 90% were former smokers. The mean age was 40 years
*At the time of participation, most commonly used flavors were fruits, followed by sweets.
*'''Most participants (68.3%) were switching between flavours on a daily basis or within the day''', with former smokers switching more frequently. More than half of the study sample mentioned that they like the variety of flavours and that the taste gets blunt from long-term use of the same flavour. The average score for importance of flavours variability in reducing or quitting smoking was 4 (“very important”). Finally, the majority of participants stated that restricting variability of flavours would make the EC experience less enjoyable while almost half of them answered that it would increase craving for tobacco cigarettes and would make reducing or completely substituting smoking less likely.
*The results of this survey indicate that EC liquid flavourings play a major role in the overall experience of dedicated users and support the hypothesis that they are important contributors in reducing or eliminating smoking consumption.
*[https://sci-hub.st/10.3390/ijerph10127272# PDF Version]
*Citation: Farsalinos, K., Romagna, G., Tsiapras, D., Kyrzopoulos, S., Spyrou, A., & Voudris, V. (2013). Impact of Flavour Variability on Electronic Cigarette Use Experience: An Internet Survey. International Journal of Environmental Research and Public Health, 10(12), 7272–7282. doi:10.3390/ijerph10127272

===2006: [https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2000.tb06686.x Tobacco Dependence: Global Public Health Potential for New Medications Development and Indications]=== 


*The marketing of a mint-flavored form of nicotine gum in the United States increased the market for nicotine gum by more than 25% and contributed to increasing numbers of smokers finding a treatment that was acceptable and thereby successfully quitting smoking.
*There is clearly a need for increased forms of nicotine delivery, possibly including those that more closely mimic the pharmacokinetics of cigarettes.
*PDF Version
*Citation: HENNINGFIELD, J. E., FANT, R. V., GITCHELL, J., & SHIFFMAN, S. (2006). Tobacco Dependence: Global Public Health Potential for New Medications Development and Indications. Annals of the New York Academy of Sciences, 909(1), 247–256. doi:10.1111/j.1749-6632.2000.tb06686.x

=Use of Flavors (Youth to Sr. Citizens)= 

===2021: [https://thr.ams3.cdn.digitaloceanspaces.com/strapi/0cbd3b34cef86dad0032528c324d2f7b.pdf THE CASE FOR FLAVOURS IN TOBACCO HARM REDUCTION, TO SAVE LIVES]===
*Unfortunately, several governments are contemplating banning flavours in ENDS, apparently to prevent youth initiation. This review argues for the responsible and regulated use of flavours, to maximise the harm reduction effect of ENDS and its role in smoking cessation.
*Report by: Konstantinos Farsalinos, MD, MPH
*[https://www.youtube.com/watch?v=BwlJVEBk1o8&t=121s Webinar]
**This webinar discussed the above flavors report and took place on 15 December 2021, and featured Dr Konstantinos Farsalinos, Dr Delon Human, Dr Kgosi Letlape, Prof Heino Stöver, and Charles A. Gardner, PhD.

===2020: [https://pubmed.ncbi.nlm.nih.gov/33748862/ Choice and variety-seeking of e-liquids and flavour (flavor) categories by New Zealand smokers using an electronic cigarette: a longitudinal study]=== 


*'''Variety-seeking behaviour (behavior) was common and typically reported within the first 12 weeks of participants’ e-cigarette-assisted attempt to transition away from smoking.'''
*Policies allowing diverse e-liquid flavours at specialist stores could support users’ variety-seeking and potentially create opportunities to couple e-liquid purchasing occasions with cessation advice during the first months of a transition attempt.
*Citation: Mei-Ling Blank, MPH, Janet Hoek, PhD, Choice and variety-seeking of e-liquids and flavour categories by New Zealand smokers using an electronic cigarette: a longitudinal study, Nicotine & Tobacco Research, , ntaa248, doi:10.1093/ntr/ntaa248

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022703/ Changing patterns of first e-cigarette flavor used and current flavors used by 20,836 adult frequent e-cigarette users in the USA]=== 


*Adult frequent e-cigarette users in the USA who have completely switched from smoking cigarettes to using e-cigarettes are increasingly likely to have initiated e-cigarette use with non-tobacco flavors and to have transitioned from tobacco to non-tobacco flavors over time. '''Restricting access to non-tobacco e-cigarette flavors may discourage smokers from attempting to switch to e-cigarettes'''.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022703/pdf/12954_2018_Article_238.pdf PDF Version]
*Citation: Russell C, McKeganey N, Dickson T, Nides M. Changing patterns of first e-cigarette flavor used and current flavors used by 20,836 adult frequent e-cigarette users in the USA. Harm Reduct J. 2018 Jun 28;15(1):33. doi: 10.1186/s12954-018-0238-6. PMID: 29954412; PMCID: PMC6022703.

===2015: [https://academic.oup.com/ntr/article-abstract/17/10/1255/1028251?redirectedFrom=fulltext The Impact of Flavor Descriptors on Nonsmoking Teens’ and Adult Smokers’ Interest in Electronic Cigarettes]=== 


*Nonsmoking teens’ interest in e-cigarettes was very low.
*Adult smokers’ interest was significantly higher overall and for each flavor.
*Teen interest did not vary by flavor, but adult interest did.
*Past-30-day adult e-cigarette users had the greatest interest in e-cigarettes, and their interest was most affected by flavor.
*'''Nonsmoking teens who had never tried e-cigarettes had the lowest interest in flavors''', followed by adults who had never tried e-cigarettes
*[https://www.casaa.org/wp-content/uploads/Shiffman-on-flavors-1255-62.pdf PDF Version]
*Citation: Saul Shiffman, PhD, Mark A Sembower, MS, Janine L Pillitteri, PhD, Karen K Gerlach, PhD, MPH, Joseph G Gitchell, BA, The Impact of Flavor Descriptors on Nonsmoking Teens’ and Adult Smokers’ Interest in Electronic Cigarettes, Nicotine & Tobacco Research, Volume 17, Issue 10, October 2015, Pages 1255–1262, doi: 10.1093/ntr/ntu333

===2013: [https://www.sciencedirect.com/science/article/abs/pii/S1054139X12004090 Adolescent Males' Awareness of and Willingness to Try Electronic Cigarettes]=== 


*Only two participants (< 1%) had previously tried e-cigarettes.
*Among those who had not tried e-cigarettes, most (67%) had heard of them. Awareness was higher among older and non-Hispanic adolescents.
*Nearly 1 in 5 (18%) participants were willing to try either a plain or flavored e-cigarette, but '''willingness to try plain versus flavored varieties did not differ'''.
*Smokers were more willing to try any e-cigarette than nonsmokers.
*Nonsmokers who had more negative beliefs about the typical smoker were less willing to try e-cigarettes.
*[https://sci-hub.st/10.1016/j.jadohealth.2012.09.014# PDF Version]
*Citation: Pepper, J. K., Reiter, P. L., McRee, A.-L., Cameron, L. D., Gilkey, M. B., & Brewer, N. T. (2013). Adolescent Males’ Awareness of and Willingness to Try Electronic Cigarettes. Journal of Adolescent Health, 52(2), 144–150. doi:10.1016/j.jadohealth.2012.09.014

=Youth= 

===2020: [https://cei.org/issue_analysis/perverse-psychology/ Report Summary: Perverse Psychology How Anti-Vaping Campaigners Created the Youth Vaping “Epidemic”]=== 


*It is reasonable for anti-tobacco advocates to worry about youth experimentation with nicotine, but the evidence is clear that their interventions have backfired and made the problem worse. Their attempts to dissuade teenagers from vaping increased their awareness of the behavior, made it more attractive, and convinced them that everyone around them was doing it.
*Anti-tobacco advocates argue that the government can end the “epidemic” by raising the minimum tobacco age to 21, '''banning non-tobacco e-cigarette flavors''', and increasing funding for anti-vaping education. But, as this paper has demonstrated, '''these measures will not only fail, they will actually make matters worse by increasing the coolness of vaping and youth attraction to it'''.
*Teen vaping did not escalate despite the increased anti-vaping messaging. Adolescents’ curiosity and subsequent experimentation with vaping rose because of anti-vaping messaging.
*[https://cei.org/sites/default/files/Michelle%20Minton%20-%20Perverse%20Psychology.pdf PDF of Full report]

===2020: [https://www.nber.org/papers/w26811 Paper: Intended and Unintended Effects of Banning Menthol Cigarettes]=== 


*'''Menthol bans significantly increased non-menthol cigarette smoking among youths, resulting in no overall net change in youth smoking rates'''.
*Menthol bans shifted smokers’ cigarette purchases away from grocery stores and gas stations to First Nations reserves (where the menthol bans do not bind).
*[https://sci-hub.st/10.3386/w26811# PDF Full Paper]

===2020: [https://www.youtube.com/watch?v=O4_l-klxqCQ Video: Vaping: what people are getting wrong]=== 


*The Economist
*A youth vaping “epidemic” and a mysterious outbreak of lung disease in America has led to curbs on e-cigarette flavours. A backlash against vaping is perpetuating myths about nicotine-based e-cigarette products that are not backed up by scientific research. (UK / English)

===2019: Article: [https://www.clivebates.com/the-us-vaping-flavour-ban-twenty-things-you-should-know/ The US vaping flavour (flavor) ban: twenty things you should know]=== 


*A well researched article that touches on many of the myths and fears about youth use of flavored vapor products.
*[https://www.clivebates.com/documents/Flavours20Nov2019.pdf PDF Version]

===2017: Blog: [http://mommavape.blogspot.com/2017/12/paint-me-green-and-hear-me-roar.html Confessions of an e-liquid mixologist]=== 


*Certain things really bother me. Like when anti-tobacco activists do things to destroy my pride in being an ex-smoker and helping other people quit smoking. The most hurtful thing of all, is to pervert the effort I put into creating flavors of e-liquids to appeal to adult smokers and accuse me of marketing to children, of trying to addict the next generation of kids on nicotine.
*Not once did I create a flavor and go “hmmmm, I bet a 12 year old would like this”. Not once. I’m not a monster, I’m a mom, an aunt, a grandma, and a great grandma. All I wanted to do is help people quit smoking so they could live long enough to enjoy their extended families. I wanted to help people quit smoking so kids would no longer be exposed to 2nd hand smoke. I wanted to make the world a better place.

=Addressing Myths About Flavors= 

===2020: Article: [https://vaping360.com/learn/popcorn-lung-diacetyl/ Does Diacetyl in Vaping Cause Popcorn Lung?]=== 


*While almost anything is possible, there’s simply no evidence that vaping causes popcorn lung.

===2019: Cancer Research UK: [https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/does-vaping-cause-popcorn-lung Does vaping cause popcorn lung?]=== 


*No. There’s no good evidence that e-cigarettes could cause the lung condition called popcorn lung. There’s been no confirmed cases of popcorn lung reported in people who use e-cigarettes.

===2019: [https://www.cmaj.ca/content/re-vape-related-popcorn-lung-debunked-years-ago RE: Vape related "Popcorn Lung" debunked years ago]=== 


*There is 750x more diacetyl in a pack of cigarettes than there is in a days worth of vaping nicotine fluid, and to date we have no confirmation that smokers are getting popcorn lung.

===2018: [http://www.ecigarette-research.org/research/index.php/research/2018/262-flavors Paper: E-cigarette flavors and aldehyde emissions: another failure to verify findings from a previous study]=== 


: Our results were revealing in identifying a very small contribution of flavorings on aldehyde emissions. In fact, aldehyde levels were so low that consumption of 5 grams liquid per day would expose vapers to less formaldehyde and acetaldehyde than just staying at home and breathing air. For acrolein, exposure was orders of magnitude lower compared to NIOSH-defined recommended safety limits. To give you an idea of the differences in results, the authors of the original study found up to 7000 ug/g formaldehyde, while we found a maximum of 62 ug/g.
*2017: [https://sci-hub.se/10.1016/j.fct.2018.02.059 Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?]
: In conclusion, we confirmed that flavouring compounds can contribute to aldehyde emissions from ECs, but such contribution, detected in only 3 liquids and two flavours herein, was minimal.

===2017: [https://pubs.acs.org/doi/10.1021/acs.est.6b06030 Comment on “Flavoring Compounds Dominate Toxic Aldehyde Production during E Cigarette Vaping”]=== 


*We would like to point out that the finding is in a stark contrast to previous results.
*The high levels only happen under dry puff conditions, something avoided by vapers as it is very unpleasant.

===2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/234-bo Medical journal MISPRESENTS a case of hypersensitivity pneumonitis as popcorn lung disease caused by e-cigarette]=== 


*It was shocking to see a public statement reporting a case of popcorn lung disease in a patient using e-cigarettes. The title of the public release is: “Case report finds 'popcorn lung' in patient using e-cigarettes. Report points to possibility of diacetyl, a flavoring agent in e-cigarettes, to bronchiolitis obliterans syndrome”
*The article then goes on to explain why it can’t be popcorn lung and calls for the retraction of the study.

===2015 [http://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking]=== 


*There's just one minor fact that is omitted completely in the article, as well as in all the media coverage.
*That fact: All conventional cigarettes produce tobacco smoke that contains diacetyl, and the levels of diacetyl in cigarettes are a lot higher than those produced by e-cigarettes.

=Quotes / Graphics= 

===Scott Gottlieb, MD - Former USA FDA Commissioner=== 
[https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-efforts-reduce-tobacco-use-especially-among-youth Source]


[[File:GottliebFlavors.jpg|Scott Gottlieb on Flavors]]
 

===American Association of Public Health Physicians=== 


[[File:AAPHP.jpg|AAPHP flavor statement]]

===Observation on the variety of flavored products used=== 


[[File:Flavors_for_smoking_cessation.jpg|NRT vs. ENDS: Does it matter?]]

===American Academy of Pediatricts=== 


[[File:Flavored_NRT.jpg|Flavored NRT ]]

===FDA approved manufacturers of Nicotine Replacement Therapy understand the importance of flavors=== 


[[File:Nicorette_flavors.jpg|FDA approved NRT comes in flavors]]

===Age demographics of people who eat cotton candy=== 


[[File:Cotton_candy.png|Cotton Candy]]

===Senator Dick Durbin endorses banning flavors (1)=== 


[[File:Senator_Durbin_Ice_Cream.jpg|Senator Durbin Ice Cream ]]

===Senator Dick Durbin endorses banning flavors (2)=== 


[[File:Senator_Durbin_Candy.png|Senator Durbin Candy]]

=Further Reading=
===2023: Yale School of Public Health: [https://ysph.yale.edu/news-article/tobacco-purchases-rise-following-restrictions-on-e-cigarette-sales/ Tobacco purchases rise following restrictions on e-cigarette sales]===
===2021: Policy Analyst Testimony: [https://www.cga.ct.gov/2021/PHdata/Tmy/2021SB-00326-R000208-Stroud,%20Lindsey,%20Policy%20Analyst-Taxpayers%20Protection%20Alliance-TMY.PDF Testimony before the Connecticut Public Health Committee Regarding Prohibiting the Sale of Flavored Tobacco and Vapor Products]===
===2021: Commentary: [https://www.myjournalcourier.com/opinion/article/Commentary-Lindsey-Stroud-Want-fewer-teen-16184278.php Want fewer teen smokers? Stop all the bans]===
===2020: Policy Paper: [https://241yjo5ffc43s84vz4462arn-wpengine.netdna-ssl.com/wp-content/uploads/2020/09/WHY-VAPE-FLAVORS-MATTER-POLICY-PAPER.pdf Why Vape Flavors Matter]===
===2020: Policy Blog: [https://vaping.org/yale-study-finds-that-vaping-flavors-help-adults-quit/ YALE STUDY FINDS THAT VAPING FLAVORS HELP ADULTS QUIT]===
===2020: Policy Blog: [https://reason.org/commentary/montana-should-reject-proposed-ban-on-flavored-vaping-products/ Montana Should Reject Proposed Ban on Flavored Vaping Products]===
===2020: Opinion: [https://insidesources.com/flavors-arent-main-driver-of-youth-e-cigarette-use/ Flavors Aren’t Main Driver of Youth E-Cigarette Use]===
===2020: Policy Blog: [https://reason.org/commentary/how-californias-flavored-tobacco-ban-will-hurt-communities-and-budgets/ How California’s Flavored Tobacco Ban Will Hurt Communities and Budgets]===
===2020: Policy analyst Testimony: [https://www.house.leg.state.mn.us/comm/docs/3437294b-d481-4a34-b22c-887092b85054.pdf Testimony before the Minnesota House Committee on Commerce]===
===2020: Flavor Ban Letter: [https://vaping.org/ava-urges-florida-governor-to-veto-backdoor-flavor-ban-bill/ AVA URGES FLORIDA GOVERNOR TO VETO BACKDOOR FLAVOR BAN BILL]===
===2020: Policy Blog: [https://reason.org/events/the-costs-and-unintended-consequences-of-tobacco-and-vaping-flavor-bans/ The Costs and Unintended Consequences of Tobacco and Vaping Flavor Bans]===
===2020: Policy Blog: [https://reason.org/commentary/in-2020-congress-replaced-war-on-marijuana-with-a-war-on-flavored-tobacco-products/ In 2020, Congress Replaced the War on Marijuana With a War on Flavored Tobacco Products]===
===2020: Policy Blog: [https://reason.org/commentary/cdc-survey-shows-flavors-arent-driving-youth-vaping/ CDC Survey Shows Flavors Aren’t Driving Youth Vaping]===
===2020: Policy Blog: [https://reason.org/commentary/the-negative-impacts-of-massachusetts-flavored-tobacco-ban/ The Negative Impacts of Massachusetts’ Flavored Tobacco Ban]===
===2019: Policy Paper: [https://www.heartland.org/_template-assets/documents/Tobacco%20Harm%20Reduction%20pdf.pdf TOBACCO HARM REDUCTION 101: A GUIDEBOOK FOR POLICYMAKERS]===
===2019: Article: [https://dailygazette.com/2019/07/08/editorial-vote-no-on-flavored-vaping-ban/?fbclid=IwAR1zS8EeRnRi8ItYlqDa68emLywJpHUcccRRT1SOPdZoGROzk7Taea8XkqA EDITORIAL: Vote no on flavored vaping ban]===
===2019: [https://vaportechnology.org/wp-content/uploads/2019/11/Dunham-Economic-Impact-of-Flavor-Ban-11-21-19.pdf The Economic Impact of a Ban on Flavored Vapor Products ]===
*[https://vaportechnology.org/wp-content/uploads/2019/11/New-Economic-Analysis-Demonstrates-Significant-Negative-Impact-of-a-National-Flavor-Ban50808.pdf NEW ECONOMIC ANALYSIS DEMONSTRATES SIGNIFICANT NEGATIVE IMPACT OF A NATIONAL FLAVOR BAN ]
===2019: Policy Blog: [https://reason.org/commentary/albanys-proposed-flavored-tobacco-ban-misses-the-mark/ Albany’s Proposed Flavored Tobacco Ban Misses the Mark]===
===2019: Policy Blog: [https://reason.org/commentary/the-public-health-case-for-e-cigarette-flavors/ The Public Health Case for E-Cigarette Flavors]===
===2019: Policy Blog: [https://reason.org/wp-content/uploads/michigan-e-cigarette-flavors-explainer.pdf E-Cigarette Flavor Ban Creates Public Health Problems]===
===2018: Testimony to FDA: [https://reason.org/commentary/comments-on-fdas-advance-notice-of-proposed-rulemaking-on-flavored-tobacco-products/ Comments on FDA's Advance Notice of Proposed Rulemaking on Flavored Tobacco Products]===
===2018: Policy Blog: [https://reason.org/commentary/san-francisco-flavored-vapes-and-the-next-prohibition-disaster/ San Francisco, Flavored Vapes, and the Next Prohibition Disaster]===
===2018: Policy Blog: [https://reason.org/commentary/californias-plan-to-ban-vaping-flavors-would-hurt-public-health/ California’s Plan to Ban Vaping Flavors would Hurt Public Health]===
===2017: Blog: [http://tobaccoanalysis.blogspot.com/2017/05/vape-shop-air-sampling-by-california.html Vape Shop Air Sampling by California State Health Department Suggests that Secondhand Vape Exposure is Minimal]===
===2017: Blog: [https://www.clivebates.com/flavors Are e-liquid flavours really 'hooking another generation of kids'?]===

=Other Resources=

===[https://docs.google.com/document/d/1CWfu0QLj347Ud07tb9NdNWESXZRqAzW9MX_VbU_NAss/edit?usp=sharing Document of pre-written tweets about flavors]===

=Suggested Studies, Papers, Surveys, and Articles to Add to This Page= 
*If you prefer not to add information to this page yourself, drop the links here and one of our editors will do it for you

===2026: [https://pubmed.ncbi.nlm.nih.gov/42004573/ E-CIGARETTE FLAVOR RESTRICTIONS' EFFECTS ON TOBACCO PRODUCT SALES]===

===2025: [https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5705282 Restricting Sales of Flavored Nicotine Vaping Products: Effects on Cigarette and Nicotine Vaping Product Sales in Canada]===

===2024: [https://pubmed.ncbi.nlm.nih.gov/39787830/ The impact of non-tobacco e-cigarette flavoring on e-cigarette uptake, cigarette smoking reduction, and cessation: A secondary analysis of a nationwide clinical trial]===

===2024: [https://jamanetwork.com/journals/jama-health-forum/fullarticle/2828404 Flavored E-Cigarette Sales Restrictions and Young Adult Tobacco Use]===

=Page Editor Instructions= 
*'''PAGE EDITORS - Please add Studies, Surveys, Papers in this format to keep page consistent for all viewers.'''
**Topic
**Year (list new to old) Name of Study (In link format to the study)
**Note here if animal study (leave blank if not)
**Brief Summary
**Link to PDF Version
**Citation
**Acknowledgements (funded by, helped by)
**Keywords
**Other


[[Category:Studies, Surveys, and Papers]]
[[Category:Media - Movies, Videos, Vlogs, Blogs, OpEds, News, etc.]] [[Category: FAQ Question]]
</translate>

Nicotine - Retracted Studies, Papers, and Articles

2026-04-26T10:47:43Z

Skip: /* 2026: RETRACTED: Evidence on vaping e-cigarettes as a risk factor for cancer: A systematic review */

[[File:Corrections.png|center|]]
 

<big>'''On this page, we'll explore how mistakes in published works can happen, log commentaries on some published works, and list some examples of retracted papers.'''</big>

=How Mistakes Can Happen=

==Journals==

===2024: (Preprint) [https://www.preprints.org/manuscript/202410.2456/v2 Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy]===
*"This review explores methodological considerations for maximizing the precision and accuracy of observational cohort studies assessing the risk profiles of tobacco and nicotine products. These considerations, informed by the ROBINS framework for minimizing statistical bias, are anchored in a comprehensive characterization of exposure to all tobacco products currently or formerly used, with corroboration of dose-response relationships."
**Citation: Cohen, G., & Cook, S. (2024). Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy. Preprints. https://doi.org/10.20944/preprints202410.2456.v2

===2024: [https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1433626/full Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols]===
*"Updating and improving testing standards to incorporate basic conditions of experimental quality is necessary to achieve a more objective evaluation of the risk profile of ECs, which will provide valuable information to all stakeholders (consumers, health professionals, regulators, and the industries themselves)."
**Citation: Sussman RA, Sipala FM, Ronsisvalle S and Soulet S (2024) Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols. Front. Chem. 12:1433626. doi: 10.3389/fchem.2024.1433626

===2022: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis]===
*"Studies based on cross-sectional data with no information on age of e-cigarette initiation and age of diagnosis invariably overestimate associations by including cases that were diagnosed before e-cigarette exposure. Although the authors of those studies did not make causal claims in the reports, university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."
**Citation: Rodu B, Plurphanswat N. Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Intern Emerg Med. 2023 Jan;18(1):319-323. doi: 10.1007/s11739-022-03141-3. Epub 2022 Nov 25. PMID: 36434423.
*Commentary: [https://reason.com/wp-content/uploads/2022/12/Polosa-Commentary-IAEM-2022.pdf A tale of flawed e‑cigarette research undetected by defective peer review process]
*Article: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Diseases That Studies Linked to E-Cigarettes Generally Were Diagnosed Before Subjects Began Vaping]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018638/ Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research]===
*Conclusion: "Our critical appraisal reveals common, preventable flaws, the identification of which may provide guidance to researchers, reviewers, scientific editor, journalists, and policy makers. One striking result of the review is that a large portion of the high-ranking papers came out of US-dominated research institutions whose funders are unsupportive of a tobacco harm reduction agenda..."
**Citation: Hajat C, Stein E, Selya A, Polosa R; CoEHAR study group. Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research. Intern Emerg Med. 2022 Apr;17(3):887-909. doi: 10.1007/s11739-022-02967-1. Epub 2022 Mar 24. Erratum in: Intern Emerg Med. 2022 Aug;17(5):1561. PMID: 35325394; PMCID: PMC9018638.
*Article: [https://filtermag.org/vaping-research-quality/ Researchers Expose the Pitiful Quality of Highly Cited Vaping Studies]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506048/ A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol]===
*Abstract: "The inhalation of metallic compounds in e-cigarette (EC) aerosol emissions presents legitimate concerns of potential harms for users. We provide a critical review of laboratory studies published after 2017 on metal contents in EC aerosol, focusing on the consistency between their experimental design, real life device usage and appropriate evaluation of exposure risks. All experiments reporting levels above toxicological markers for some metals (e.g., nickel, lead, copper, manganese) exhibited the following experimental flaws: (i) high powered sub-ohm tank devices tested by means of puffing protocols whose airflows and puff volumes are conceived and appropriate for low powered devices; this testing necessarily involves overheating conditions that favor the production of toxicants and generate aerosols that are likely repellent to human users; (ii) miscalculation of exposure levels from experimental outcomes; (iii) pods and tank devices acquired months and years before the experiments, so that corrosion effects cannot be ruled out; (iv) failure to disclose important information on the characteristics of pods and tank devices, on the experimental methodology and on the resulting outcomes, thus hindering the interpretation of results and the possibility of replication"
**Citation: Soulet S, Sussman RA. A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol. Toxics. 2022 Aug 29;10(9):510. doi: 10.3390/toxics10090510. PMID: 36136475; PMCID: PMC9506048.

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787926/ Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===
*Abstract: "We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and “dry puffs”. The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design."
**Citation: Soulet S, Sussman RA. Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions. Toxics. 2022 Nov 22;10(12):714. doi: 10.3390/toxics10120714. PMID: 36548547; PMCID: PMC9787926.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769337/ Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations]===
*Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context.
**Citation: Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. PMID: 29375395; PMCID: PMC5769337.

===2017: [https://pubmed.ncbi.nlm.nih.gov/28864295/ E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions]===
*The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
**Citation: Farsalinos KE, Voudris V, Spyrou A, Poulas K. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions. Food Chem Toxicol. 2017 Nov;109(Pt 1):90-94. doi: 10.1016/j.fct.2017.08.044. Epub 2017 Aug 31. PMID: 28864295.

===2015: [https://pubmed.ncbi.nlm.nih.gov/25996087/ E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions]===
*Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid.
**Citation: Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. PMID: 25996087.

==Articles/Blogs==

===2024: [https://www.thefirebreak.org/p/formaldehyde-in-vapes-exposing-another Formaldehyde In Vapes? Exposing Another Chemical Scare]===
*"The same can be said of smokers who are discouraged from switching to vapes. In the name of reducing formaldehyde exposure that is already vanishingly small, the anti-vaping warriors have effectively urged people to continue using tobacco products that contain vastly higher quantities of the compound and kill some six million users annually. They manipulate public policy and deprive people–in this case smokers looking to quit–of products that could preserve their health and even save their lives."

===2024: [https://rodutobaccotruth.blogspot.com/2024/04/are-vape-aerosols-really-toxic.html Are Vape Aerosols Really Toxic?]===
*Addresses several studies

=Science Hygiene, the efforts to correct mistakes or seek retractions by experts=
*'''Notes:'''
**'''Dates denote when comments were published, not the paper's publication date.'''
**'''Clicking the link following "Comments RE" takes you to the comment. The article the comment is addressing will be linked under "Referring to."'''

==Addiction / Dependence / Use==
*To learn more about addiction/dependence, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine_-_Addiction/Dependence Nicotine - Addiction/Dependence]

===2024: Comments RE: [https://pubpeer.com/publications/40A35E1B6BCE23874F886C76971576 E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective]===
*Waa’s “Indigenous perspective” on e‐cigarette policies claiming Māori (the Indigenous people of New Zealand) were being exploited [1] omits some important context... (Lists examples)... Finally, Māori people have diverse views on vaping. For example, the Manager of the National Tobacco Control Advocacy Service, Hapai Te Hauora said in 2019, “Do you know who has a vested interest in vaping? Anyone who is sick of losing 5,000 whānau [family] members a year to tobacco; anyone who acknowledges the growing body of research showing vaping is helping many to break free of their tobacco addiction; anyone who cares about our people”. (Mendelsohn, Glover)
**Referring to: Waa A. E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective. Addiction. 2024 May 24. Epub ahead of print. PMID: 38794822. [https://onlinelibrary.wiley.com/doi/10.1111/add.16573 doi: 10.1111/add.16573].
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16462 E-cigarettes: A framework for comparative history and policy]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16660 Evidence and policy is certainly more complex than it seems]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16597 A tobacco control policy analysis framework that extends into the future]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16577 Adopting the Berridge et al.: Framework to understand differences in the e-cigarette policy between the Nordic countries]

===2024: Comments RE: [https://pubpeer.com/publications/E128EE4F19CD39411FAFDDB6A88FED Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity]===
*Despite the authors correcting recognizing that “no trends… should be inferred” between 2020 and 2021, they infer trends between 2021 and 2022, thus making the very same error, as the artifact relates to NYTS 2021 alone, not 2021 and every year thereafter. (Selya)
**Referring to: Mattingly DT, Hart JL. Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity. JAMA Netw Open. 2024;7(2):e2354872. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814427 doi:10.1001/jamanetworkopen.2023.54872]

===2024: Comments RE: [https://pubpeer.com/publications/DEF986999C6287FCD8FD4048A0B8EE Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022]===
*"Overall, Zhang et al. improperly conclude that there is a true uptick in dual- and poly-use of nicotine and tobacco in NYTS, but did not attribute any of their findings to a well-documented methodological artifact in NYTS 2021 which renders the findings inconclusive, as (in the words of official NYTS publications) 'differences between estimates might be due to changes in methodology, actual behavior, or both.' ” (Selya)
**Referring To: Zhang, B., Bannon, O., Chen, D. T., & Filippidis, F. T. (2024). Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022. Addictive Behaviors, 152, 107970. [https://www.sciencedirect.com/science/article/pii/S0306460324000194 https://doi.org/10.1016/j.addbeh.2024.107970]

===2023: Comments RE: [https://pubpeer.com/publications/3BF65B1CBECA15D0EC1068CF8628BC#2 Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth]===
*"Readers may be interested to know that there is now a comment to the Pierce et al paper from Shiffman and Hannon. The commenters raise questions about the conclusions drawn by the original authors and report alternative analyses of the same dataset." (Gitchell)
*"To this last point, Pierce and Strong’s response now reports a relevant analysis, and it directly contradicts their assertion in the original paper: they demonstrate that dependence among JUUL users in each age cohort was not different from dependence in users of other ENDS brands (though the trend is evidently for lower dependence among JUUL users)." (Shiffman)
**Referring To: Pierce JP, Leas EC, Strong DR. Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth. Pediatrics. 2023 Apr 1;151(4):e2022059158. PMID: 36942497. doi: https://doi.org/10.1542/peds.2022-059158

===2022: Comments RE: [https://pubpeer.com/publications/1FF8B75DFC81492DEBC8E214F63098 Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study]===
*A re-analysis of the data by Foxon & Shiffman (2) revealed that those analyses did not include replicate weights as specified in guidance from the PATH study team. Foxon & Shiffman (2) show that when the above analyses are performed with the replicate weights included, the associations above are statistically non-significant. (Foxon, Shiffman)
*(2) [https://www.mdpi.com/1660-4601/20/18/6715 Full Comment]
**Referring to: Wang Y, Duan Z, Weaver SR, Popova L, Spears CA, Ashley DL, Pechacek TF, Eriksen MP, Huang J. Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study. International Journal of Environmental Research and Public Health. 2022; 19(17):10837. [https://doi.org/10.3390/ijerph191710837 https://doi.org/10.3390/ijerph191710837]

===2021: Comments RE: [https://pubpeer.com/publications/57A74561DC4B1B43B91E18A95A24A5 Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users]===
*In summary, by imputing respondents who reported that they “don’t know” which ENDS brand they used to the non-JUUL group even if they may have used JUUL, and by relying on ‘any’ JUUL use definitions which defined as JUUL users those who “usually” used a different ENDS brand, the original analysis systematically biases against the focal brand (JUUL) being studied. (Foxon, Shiffman)
*In summary, the results of Mantey et al. are invalid, because they were based on a definition of JUUL use that is not justified by the brand information in the 2020 National Youth Tobacco Survey.(Rodu)
**Referring to: Mantey DS, Case KR, Omega-Njemnobi O, Springer AE, Kelder SH. Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users. Drug Alcohol Depend. 2021 Nov 1;228:109078. Epub 2021 Sep 24. PMID: 34614433; PMCID: PMC8595823. [https://doi.org/10.1016/j.drugalcdep.2021.109078 https://doi.org/10.1016/j.drugalcdep.2021.109078]

===2019: Comments RE: [https://pubpeer.com/publications/1F7BA5A2DEC4EF71CA4E7F34C69806 Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys]===
*These (improbable) increases conflict with official data from Statistics Canada that were released shortly after the publication of the paper drawn from the Canadian Community Health Survey, with a representative sample of 65,000. (Bates)
*The Counterfactual: [https://clivebates.com/canada-takes-a-wrong-turn-after-a-flawed-paper-induces-moral-panic-about-youth-vaping-and-smoking/ Canada takes a wrong turn after a flawed paper induces moral panic about youth vaping and smoking]
**Referring to: Hammond D, Reid JL, Rynard VL, Fong GT, Cummings KM, McNeill A, Hitchman S, Thrasher JF, Goniewicz ML, Bansal-Travers M, O'Connor R, Levy D, Borland R, White CM. Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys. BMJ. 2019 Jun 20;365:l2219. Erratum in: BMJ. 2020 Jul 10;370:m2579. PMID: 31221636; PMCID: PMC6582265. [https://doi.org/10.1136/bmj.l2219 doi: 10.1136/bmj.l2219]
**[https://www.bmj.com/content/370/bmj.m2579 Corrections]: "The authors of this paper (BMJ 2019;365:l2219, doi:10.1136/bmj.l2219, published 20 June 2019) have provided an update on estimates of smoking among adolescents and vaping from the ITC Youth and Vaping Surveys conducted in Canada, England, and the United States (see supplementary file for details).
**I note with interest that another paper in BMJ includes the same red-box Correction. However with this one, upon clicking, it opens a page displaying a direct and complete explanation of the correction and a pledge that the paper itself will be updated (it has been). It would be welcome if the journal would apply the same level of rigor to the Hammond et al paper (Gitchell).

===2018: Comments RE: [https://pubpeer.com/publications/58B4D5D27C6A7C45EE3A094D324368 Prevalence and correlates of JUUL use among a national sample of youth and young adults]===
*The results from this article are uninformative, because the authors did not include simple crosstabs of the raw numbers showing the overlap in current use of ENDS, JUUL and combustible products. They failed to denote current ENDS use in the model for Table two. (Rodu)
**Referring to: Vallone DM, Bennett M, Xiao H, Pitzer L, Hair EC. Prevalence and correlates of JUUL use among a national sample of youth and young adults. Tob Control. 2019 Nov;28(6):603-609. Epub 2018 Oct 29. PMID: 30377241. [https://doi.org/10.1136/tobaccocontrol-2018-054693 https://doi.org/10.1136/tobaccocontrol-2018-054693]

===2014: Comments RE: [https://sci-hub.wf/10.1001/jamapediatrics.2014.733 Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents]===
*"In a cross-sectional study, the observed relationship between e-cigarette use and higher and more sustained levels of smoking does not imply causation. Moreover, such studies do not take into account other population characteristics, which may play a crucial role when determining potential causation.2,3 Although the authors acknowledged this limitation in the text, they ended up drawing a conclusion that misleads the public into thinking e-cigarettes are leading to smoking initiation and addiction among adolescents." (Farsalinos, Polosa)
*"Although Dutra and Glantz highlighted an important trend in e-cigarette use among our nation’s youth, failing to consider e-cigarette use in the context of other tobacco products may place undue emphasis on e-cigarettes, overshadowing the importance of the current use of multiple tobacco products as well as experimentation with cigars, smokeless tobacco, and hookah in this population." (Delnevo, Bover Manderski,Giovino)
**Referring to: Dutra LM, Glantz SA. Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. JAMA Pediatr. 2014;168(7):610–617. [https://jamanetwork.com/journals/jamapediatrics/fullarticle/1840772 doi:10.1001/jamapediatrics.2013.5488]

==Cancer==

===2024: Comments RE: [https://pubpeer.com/publications/AC3CFEABA70EC0D0AEBD1568368478 Vaping, Smoking and Lung Cancer Risk]===
*There are 10 issues with this study - Reverse Causality, Combining of Current & Ex-Smokers, Temporal Confounding, Contradiction with National Lung Cancer Trends, Absence of a Dose-Response Relationship, Unclear Definition and Consistency of Use Measures, Recall and Reporting Bias, Biological Implausibility, Uniform Effect Across Histologic Cell Types, Age at smoking initiation not adjusted for. [see commentary for further details] (Herzig)
**Referring to: Bittoni MA, Carbone DP, Harris RE (2024) Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther 9: 10229. https://doi.org/10.29011/2574-710X.10229.

==Cardiovascular==

===2024: Comments RE: [https://pubpeer.com/publications/CD0E2CD6E82EB2F69173F5A1193331#1 Electronic Cigarette Use and Myocardial Infarction]===
*"The research question posed is an important one, since the number of people who have never smoked and who report using e-cigarettes appears to have increased in recent years. However, we are concerned that the methods used in the Alzahrani study [1] make the reported findings highly suspect and the conclusion reached unlikely. This includes: 1) temporality concerns; 2) measurement, diagnosis, and biological plausibility concerns; 3) sample size concerns; 4) model design concerns; and 5) uncareful language." (Foxon, Polosa, Niaura, Cummings, Siegel, Benowitz)
**[https://twitter.com/FloeFoxon/status/1748004148987965469 Tweetorial]
*See also: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055619/ Questionable Effects of Electronic Cigarette Use on Cardiovascular Diseases From the National Health Interview Survey (NHIS, 2014-2021)]
**The study by Alzahrani made erroneous claims and overstated the association between e-cigarettes and myocardial infarction. Our replication shows that the association is driven by age and there were no statistically significant associations with other cardiovascular diseases, coronary heart diseases, and stroke.
***Referring to: Alzahrani T (November 06, 2023) Electronic Cigarette Use and Myocardial Infarction. Cureus 15(11): e48402. [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction doi:10.7759/cureus.48402]

===2022: Comments RE: [https://pubpeer.com/publications/B1574611ED725601C17C3766DB164E Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular disease. A recent analysis by my research group of data from the Population Assessment of Tobacco and Health, which contains this essential temporal information, provides definitive evidence that the results from Osei et al. are deficient and unreliable." (Rodu)
**Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Benjamin EJ, Hall ME, DeFilippis AP, Stokes A, Bhatnagar A, Nasir K, Blaha MJ. Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers. Am J Med. 2019 Aug;132(8):949-954.e2. doi: [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction#!/ 10.1016/j.amjmed.2019.02.016]. Epub 2019 Mar 8. PMID: 30853474.

===2022: Comments RE: [https://pubpeer.com/publications/D075EB2EED18CA0311BAC77C783777 Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use]===
*"The study by Vindhyal et al. used the National Health Interview Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
**Referring to: Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS. Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use. Cureus. 2020 Aug 8;12(8):e9618. [https://pubmed.ncbi.nlm.nih.gov/32923219/ doi: 10.7759/cureus.9618]. PMID: 32923219; PMCID: PMC7478662.

===2020: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-smoking-vaping-and-stroke-risk/ Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults]===
*“These findings arise from subgroup analysis involving multiple hypothesis tests and are therefore unreliable. Contrary to the authors’ claim, this study provides no evidence that vaping increases the risk of stroke accrued from smoking tobacco.” (Britton)
*“While the paper itself is careful in interpreting the finding, the press release is grossly misleading. The study provides no justification for the claim that vaping increases the risk of stroke.” (Hajek)
*"While this paper highlights the need to continue studying the potential health effects of e-cigarette use, the results should be interpreted with caution as the observed associations may be simply due to unmeasured confounding and reverse causality.” (Shahab)
**Referring to: Parekh T, Pemmasani S, Desai R. Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults. Am J Prev Med. 2020 Mar;58(3):446-452. [https://pubmed.ncbi.nlm.nih.gov/31924460/ doi: 10.1016/j.amepre.2019.10.008]. Epub 2020 Jan 7. PMID: 31924460.

===2020-2022: Comments RE: [https://pubpeer.com/publications/E4180AE40B2A0F076D7D07CE0B7961 Association Between Electronic Cigarette Use and Myocardial Infarction]===
*Multiple comments:
**"The study by Alzahrani et al. used data from the National Health Interview Survey, which contains no information about when participants started to smoke or vape, and when they were diagnosed with a myocardial infarction." (Rodu)
**"E-cigarettes first appeared in the US at about 2009 and their use picked up from about 2013. In the cohorts from 2014 and 2016 that this study used, most participants with a history of MI can be expected to have had their MI before they tried e-cigarettes...The authors’ conclusions are thus misleading on an important public health issue. The article has been used e.g. to claim that vaping increases risk of cardiovascular disease by the WHO Director Ghebreyesus (DOI: 10.1016/S0140-6736(19)31730-1). The data that the paper reports show no such thing." (Hajek)
*See also: [https://www.ajpmonline.org/article/S0749-3797(21)00290-7/fulltext 2021]
**"Alzahrani and colleagues rightly point out that their models test for and thus demonstrate statistically independent effects of smoking and vaping, but if vaping and smoking are not actually independent contributors to identifying MI occurrence—that is, if the association between e-cigarette use and MI occurrence varies as a function of combustible cigarette use—then the main-effects model cannot be used to draw conclusions about the association between e-cigarette use and MI, independent of (or regardless of) one's history of combustible cigarette use." (Critcher, Siegel)
*See also: [https://sci-hub.wf/10.1016/j.amepre.2019.03.012 2019]
**"As the debate on the risks−benefits of electronic-cigarettes continues, a rigorous evidence base is critical. Although determining whether the use of e-cigarettes carries excess risk for future MI is important, it is not possible through the analysis of cross-sectional data, such as the National Health Interview Survey data, from which temporality cannot be inferred. Equally important, we were unable to replicate the authors’ findings. Given the importance of this topic to public health, we request that the authors provide a full and comprehensive explanation for the discrepancies noted and temper their conclusions about “increased risk of myocardial infarction” to reflect the limitations of cross-sectional data." (Bover Manderski, Singh, Delnevo)
* See also: [https://sci-hub.wf/10.1016/j.amepre.2018.06.007 2018]
**"Of concern,however, is the fact that 95% of EC users were also former or current tobacco cigarette (TC) smokers, and the timing of the MI relative to onset of EC use is unknown. (Middlekauff, Gornbein)
*See also: [https://sci-hub.se/10.1016/j.amepre.2018.11.013 2018]
**"Our findings show the well-established limitations of cross-sectional studies, which cannot justify any claims about causal inference, as mentioned in the conclusion by Alzahrani and colleagues.1 Therefore, the conclusion of their study is incorrect and should be revised." (Farsalinos, Niaura)
***Referring to: Alzahrani T, Pena I, Temesgen N, Glantz SA. [http://Association%20Between%20Electronic%20Cigarette%20Use%20and%20Myocardial%20Infarction Association Between Electronic Cigarette Use and Myocardial Infarction]. Am J Prev Med. 2018 Oct;55(4):455-461. doi: 10.1016/j.amepre.2018.05.004. Epub 2018 Aug 22. Erratum in: Am J Prev Med. 2019 Oct;57(4):579-584. PMID: 30166079; PMCID: PMC6208321.

==Cessation==
To learn more about smoking cessation, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]

===2024: Comments RE: [https://www.linkedin.com/posts/jeffrey-l-weiss_publichealth-mondaythoughts-thoughtleadership-activity-7231288859165143042-XOSF?utm_source=combined_share_message&utm_medium=member_desktop Adult Smoking Cessation — United States, 2022]===
*"Concealing important information is not meaningfully different from disseminating falsehoods. Smokers who have been unable or unwilling to quit all use of nicotine with traditional smoking cessation medicines deserve to know that they still have alternatives. It should be unacceptable that the “lead federal agency for comprehensive tobacco prevention and control” would keep potentially life-saving information from them." (Weiss)
***Referring to: VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641. DOI: http://dx.doi.org/10.15585/mmwr.mm7329a1

===2024: Comments RE: [https://pubpeer.com/publications/A21E464F1BA2A64B02D7ABF3A88965 Declines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surge]===
*"However, the authors’ conclusions are based on questionable methodological decisions and flawed analyses. Most notably:
**A. The joinpoint analysis of declining cigarette smoking is incorrectly conducted, in a way that obscures more rapid declines in current cigarette smoking after 2002;
**B. Rather than conducting a standard analysis (i.e., a weighted and adjusted analysis of e-cigarette use and smoking trends), authors instead base their conclusions on tallying states that meet certain ad hoc and stringent criteria for (unadjusted) e-cigarette use and smoking trends; and
**C. Analyses focus on an inappropriately narrow time window that does not fully capture the relevant dynamics. Together these flaws substantially underestimate the degree to which e-cigarettes may have displaced or offset cigarette smoking among youth and young adults.
**Moreover, the conclusion that e-cigarette uptake is independent of the declines in cigarette smoking runs counter to a large and varied body of evidence that e-cigarettes substitute for or displace cigarettes. The authors only discuss two such papers, attempting to undermine their conclusions using some of the same flaws that underlie their own analyses, and neglect to mention the larger body of evidence. Together, this yields an article that could cause readers to hold a distorted view of the available evidence on these important issues." (Selya, Gitchell, Foxon, Sembower, Niaura)
***Referring to: Pierce JP, Luo M, McMenamin SB, et alDeclines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surgeTobacco Control Published Online First: 08 November 2023. [https://tobaccocontrol.bmj.com/content/early/2023/11/08/tc-2022-057907 doi: 10.1136/tc-2022-057907]

===2016-2020: Comments RE: [https://pubpeer.com/publications/E2628F04937D0DBD870E115CB41C8B E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis]===
*Multiple Comments, many linking to more information
**"The most obvious issue is that the result is based on studies that have no bearing on whether e-cigarettes are effective or not. This is because vapers who successfully quit smoking were excluded and only those who failed to do so were retained. The studies were not at fault, they were just not set up to evaluate quit rates in smokers who try and not try vaping. The fault is with misinterpreting their results. The letter in LRM referenced above provides more details." (Hajek)
*[https://www.sciencemediacentre.org/expert-reaction-to-meta-analysis-looking-at-e-cigarette-use-and-smoking-cessation/ Expert Reaction]
**“Publication of this study represents a major failure of the peer review system in this journal.” (West)
**"The current paper represents the latest attempt to bring together the existing literature on e-cigarettes for smoking cessation. While its breadth is to be commended, its conclusions (that e-cigarettes don’t work for smoking cessation) are at best tentative and at worst incorrect. The main reason for this is that attempting to directly compare the results of a body of literature that uses such a wide range of study designs and includes such variable (and often poorly defined) populations and outcomes is difficult, if not impossible. Some of the observational studies included in the review, in particular, suffer from a range of limitations that don’t allow us to reliably assess whether e-cigarettes help smokers quit." (Bauld)
**“Evidence from practice in England shows that two out of three smokers who combined e-cigarettes with additional expert support from a local stop smoking service quit successfully and while dual use is a complex issue, many vapers report using an e-cigarette to cut down and ultimately quit." (O'Connor)
**“This review is grossly misleading in my opinion. There are several problems with the way studies were selected and used, but the main flaw is simple, though not easy to spot. The studies that are presented as showing that vaping does not help people quit only recruited people who were currently smoking and asked them if they used e-cigarettes in the past. This means that people who used e-cigarettes and stopped smoking were excluded. The same approach would show that proven stop-smoking medications do not help or even undermine quitting." (Hajek)
**“This review is not scientific. The information included about two studies that I co-authored is either inaccurate or misleading. In addition, the authors have not included all previous studies they could have done in their meta-analysis. I believe the findings should therefore be dismissed. I am concerned at the huge damage this publication may have – many more smokers may continue smoking and die if they take from this piece of work that all evidence suggests e-cigarettes do not help you quit smoking; that is not the case." (McNeill)
*[https://clivebates.com/who-will-be-duped-by-error-strewn-meta-analysis-of-e-cigarette-studies/ Who will be duped by error-strewn ‘meta-analysis’ of e-cigarette studies?]
**"There are multiple challenges with interpreting the e-cigarette studies routinely appearing in the scientific literature – and over-interpretation is all too easy or even deliberate." (Bates)
*[https://web.archive.org/web/20151026231500/http://truthinitiative.org/sites/default/files/2015.06.30%20E-Cig%20FDA%20Workshop%20Docket%20FINAL.pdf Legacy Foundation (now Truth Initiative) submission to the FDA]
**"While the majority of the studies we reviewed are marred by poor measurement of exposures and unmeasured confounders, many of them have been included in a meta-analysis that claims to show that smokers who use e-cigarettes are less likely to quit smoking compared to those who do not.[73] This meta- analysis simply lumps together the errors of inference from these correlations. As described in detail above, quantitatively synthesizing heterogeneous studies is scientifically inappropriate and the findings of such meta-analyses are therefore invalid."
**"Findings from the studies with the strongest methodologies suggest that e-cigarettes are effective in helping adult smokers to quit or to reduce their cigarette consumption and that rates of smoking cessation with e-cigarettes are similar to rates of cessation with nicotine replacement therapy."
*[https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(16)30024-8.pdf Correspondence]
**"There are other problems—such as selective inclusion of studies, and selective reporting of data from studies that were included —and limitations the authors acknowledge in the text but ignore in their conclusions. Detailed criticism of the methods is, however, not needed, because lumping incongruous studies together—which were mostly not designed to evaluate the efficacy of e-cigarettes, and contain no useful information on this topic unless misinterpreted—makes no scientific sense in the first place." (Hajek, McRobbie, Bullen)
*[https://antithrlies.com/2016/01/17/sunday-science-lesson-what-is-meta-analysis-and-why-was-glantzs-inherently-junk/ Sunday Science Lesson: What is “meta-analysis”? (and why was Glantz’s inherently junk?)]
**"Glantz’s meta-analysis is not just junk science because of details about the studies, though those are problems in themselves. It is junk science because there are probably not even two of the studies in his collection that are similar enough to average together, let alone all of them." (Phillips)
***Referring to: Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016 Feb;4(2):116-28. [https://pubmed.ncbi.nlm.nih.gov/26776875/ doi: 10.1016/S2213-2600(15)00521-4]. Epub 2016 Jan 14. PMID: 26776875; PMCID: PMC4752870.

==COVID==

===2022: Comments RE: [https://pubpeer.com/publications/362B01D2B4E5398302F22585990F19#1 Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review]===
*"It is important to state that there is no empiric evidence of transmission of the SARS-CoV-2 virus or any other pathogen through vaping expirations. None of the sources cited by the authors on this issue (references cited in the first paragraph above) provide such evidence, they merely speculate about it in very vague general terms.
*Given the lack of experimental detection, the potential plausibility and scope of this pathogen transmission should be discussed through well structured models based on the theory and data of pathogen transmission mechanisms. Unfortunately, the authors missed three extensive articles in which we undertook this task (links to the articles). (Sussman)
**Referring to: Singhal S, Degano C, Berenbaum E, Keller-Olaman S. Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review. [https://pubmed.ncbi.nlm.nih.gov/35881057/ J Can Dent Assoc. 2022 Jan;88:m1]. PMID: 35881057.

===2020: Comments RE: [https://pubpeer.com/publications/CEB008BBD48F89272321EB50092793 Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19]===
*Multiple Comments:
**"This article is getting severe criticism on Twitter. This thread summarises one issue and links to threads on other, more classic, problems." (Brown) Further comments by the same author (Brown) point out some errors in tables.
**"The authors surveyed and controlled for socioeconomic factors, ethnicity and compliance with confinement precautions, but not for other risk behaviors besides smoking or vaping (such as alcohol drinking, substance usage, unprotected sex). The lack of this important comparative context further weakens the conclusions of this study." (Sussman)
**"Flaws in the paper itself are only one part of the problem that needs to be addressed by the authors. The other is the public relations offensive mounted on the back of the paper once it was published in the Journal of Adolescent Health on August 11." "Unsurprisingly, such an incendiary claim generated considerable media coverage, even though there is no basis for it in fact or evidence." "Finally, there was a political dimension. On the same day as the article was published, August 11, 2020, Illinois Congressman Raja Krishnamoorthi, Chairman of the Subcommittee on Economic and Consumer Policy, found time to write a press release and letter to the Commissioner of the Food and Drug Administration, Dr. Stephen Hahn demanding FDA "clear the market of e-cigarettes" in response to the study." (Bates)
*See Also:[https://www.qeios.com/read/A58MQC Qeios 1]
**"In this brief peer review, we argue that the data reported by Gaiha et al (https://doi.org/10.1016/j.jadohealth.2020.07.002) regarding associations between vaping and COVID-19 testing are so suspect that any conclusions drawn from it cannot be relied upon. We discuss six main areas of concern and conclude that the paper should be retracted." (Gitchell, Kleykamp, Niaura, Shiffman, Cummings, Sweanor, Abrams)
*[https://www.qeios.com/read/TCEJ7G Qeios 2]
**"In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study." (Farsalinos, Niaura)
***Referring to: Gaiha SM, Cheng J, Halpern-Felsher B. Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19. J Adolesc Health. 2020 Oct;67(4):519-523. [https://www.jahonline.org/article/S1054-139X(20)30399-2/fulltext doi: 10.1016/j.jadohealth.2020.07.002]. Epub 2020 Aug 11. PMID: 32798097; PMCID: PMC7417895.

==Diabetes and Prediabetes==

===2022: Comments RE: [https://pubpeer.com/publications/D3C8E2035BE5C164E9BC19D8D50571 E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey]===
*"The results by Atuegwu et al. are deficient and unreliable, because the authors used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease." (Rodu)
**Referring to: Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM. E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey. Drug Alcohol Depend. 2019 Dec 1;205:107692. [https://pubmed.ncbi.nlm.nih.gov/31707269/ doi: 10.1016/j.drugalcdep.2019.107692]. Epub 2019 Oct 28. PMID: 31707269; PMCID: PMC6893144.

===2022: Comments RE: [https://pubpeer.com/publications/3638F392BE76DCA7CA57ABC8E554BF#1 The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018]===
*"The study by Zhang et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Their results are deficient and unreliable, because a recent analysis by my research group provides definitive evidence that the vast majority of diseases reported by vapers in cross-sectional surveys had been diagnosed before survey participants initiated the behavior." (Rodu)
*2022 Article: [https://www.acsh.org/news/2022/03/08/ignore-headlines-theres-no-science-linking-vaping-prediabetes-16172 Ignore The Headlines: There's No Science Linking Vaping To Prediabetes] (English)
**Limitations of this study include self-report of tobacco use and lack of medical confirmation of prediabetes and other diet information
**BRFSS is a cross-sectional survey, so a causal relationship between E-cigarette use and prediabetes cannot be inferred.
***Referring to: Zhang Z, Jiao Z, Blaha MJ, Osei A, Sidhaye V, Ramanathan M Jr, Biswal S. The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018. Am J Prev Med. 2022 Jun;62(6):872-877. [https://www.ajpmonline.org/article/S0749-3797(22)00024-1/fulltext doi: 10.1016/j.amepre.2021.12.009]. Epub 2022 Mar 3. PMID: 35597566.

==EVALI==

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
**Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Flavors==
*For more information about flavors, please see our page: [https://safernicotine.wiki/mediawiki/index.php/ENDS_Flavors ENDS Flavors]

===2022: [https://pubpeer.com/publications/62DEA1F7805686A6D0172A6B69EFFA Levels of menthol, nicotine and cooling agents measured in JUUL products purchased across a three-year period]===
*The implications made about JUUL products in this study are contradicted by our own contemporaneous and detailed product and manufacturing records and are more readily explained by a methodological artifact that the authors have not fully reported, even after a direct prompt before submitting the manuscript. (Gillman)
**[https://tobaccocontrol.bmj.com/content/33/2/e1 Correction to original paper]
*The PubPeer entry from Juul Labs Inc. (JLI) raises a number of serious questions about this research, the research conduct of the authors, and the editorial practices of the journal. (Bates)
*Referring To: Yassine A, El Hage R, El-Hellani A, et al. Levels of menthol, nicotine, and cooling agents measured in JUUL products purchased across a three-year period Tobacco Control 2022;31:s234-s237. [https://doi.org/10.1136/tc-2022-057506 https://doi.org/10.1136/tc-2022-057506]

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
*Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Gateway==
*To learn more about Gateway, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_are_a_gateway_to_smoking Myth: Alternative nicotine products are a gateway to smoking]

===2024: Comments RE: [https://pubpeer.com/publications/EAD2B506813B485178822E76F2377F Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey]===
*"Causation vs. association. While the authors are careful in most places to avoid claiming that this association is causal, the authors seem to ultimately conclude in favor of a (causal) gateway hypothesis, which is inappropriate given unmeasured confounding by other “common liability” factors, and the cross-sectional nature of the data." (Selya)
*Referring to: Li S, Zeng X, Di X, Liu S. Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey. Front Public Health. 2024 Jan 15;11:1272680. PMID: 38288432; PMCID: PMC10823011 [https://pubmed.ncbi.nlm.nih.gov/38288432/ doi: 10.3389/fpubh.2023.1272680]

===2022: Comments RE: [https://pubpeer.com/publications/9F3E9313EAE06ED991EE4834D69C8E Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study]===
*"The present re-analysis shows that the report of a gateway effect in the NYTS data by Harrell et al. is not supported by these data when appropriate statistical methodology is applied." (Foxon)
*Referring to: Harrell MB, Mantey DS, Chen B, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Prev Med. 2022 Nov;164:107265. Epub 2022 Sep 22. PMID: 36152819; PMCID: PMC10381788. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381788/ doi: 10.1016/j.ypmed.2022.107265]

===2021: Comments RE: [https://www-sciencemediacenter-de.translate.goog/alle-angebote/research-in-context/details/news/e-zigaretten-als-einstieg-zum-zigarettenrauchen/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en-US Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking]===
*Statements:
*; Prof. Dr. Ute Mons, Head of the Cardiovascular Epidemiology of Aging Working Group, Clinic III for Internal Medicine, Cologne University Hospital : “Since there was no statistical control for possible disruptive factors, a causal interpretation, as it is heard between the lines by the authors, is not justified. It should also be taken into account that the study period ran from 2013 to 2017, but the sale of e-cigarettes to young people in the USA was not banned until 2016.For a long time, e-cigarettes were simply more readily available to young people than conventional cigarettes."
*; Prof. Dr. Daniel Kotz, Professor of Addiction Research and Clinical Epidemiology, Institute for General Practice, University Hospital Düsseldorf : “Overall, there is no clear scientific evidence that e-cigarettes are an entry point into tobacco consumption for adolescents and young adults. It is more likely that a personal basic inclination towards nicotine products and the social environment influence the consumption of e-cigarettes or tobacco independently of one another (so-called common liability theory). International studies show that tobacco smoking is falling among adolescents, even in countries where the consumption of e-cigarettes has increased [2]. This contradicts the so-called gateway theory."
*;Prof. Dr. Heino Stöver, Managing Director of the Institute for Addiction Research Frankfurt (ISFF), Frankfurt University of Applied Sciences : “The study is not suitable for making valid statements about e-cigarettes. The main weak point of the study is that it does not take into account the motives for smoking. According to the current state of research, there is no significant causal relationship between the use of e-cigarettes and subsequent smoking. The research situation points in the opposite direction: The majority of adolescents use e-cigarettes no more than experimenting or occasionally using them. In the future, a research design is required that not only examines correlation but also real causality. Unfortunately, this is still not the case. Not even in this study. Such shortcomings underestimate the great and positive role of the e-cigarette in smoking cessation.With 95 percent fewer pollutants than conventional cigarettes, they are well suited for smokers who want to get rid of their addiction and minimize their risk."
*Refering to: John P. Pierce, Ruifeng Chen, Eric C. Leas, Martha M. White, Sheila Kealey, Matthew D. Stone, Tarik Benmarhnia, Dennis R. Trinidad, David R. Strong, Karen Messer; Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking. Pediatrics February 2021; 147 (2): e2020025122. [https://publications.aap.org/pediatrics/article/147/2/e2020025122/36274/Use-of-E-cigarettes-and-Other-Tobacco-Products-and?autologincheck=redirected 10.1542/peds.2020-025122]

===2018: Comments RE: [https://rodutobaccotruth.blogspot.com/2018/01/tobacco-gateway-report-omits-important.html Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015]===
*The Chaffee article emphasizes odds ratios but omits or obscures important contextual information. While teens who try one tobacco product are more likely to try another, the dominant gateway in the PATH survey was from no previous tobacco use to cigarettes. (Rodu)
*Referring to: Watkins SL, Glantz SA, Chaffee BW. Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015. JAMA Pediatr. 2018;172(2):181–187. [http://doi:10.1001/jamapediatrics.2017.4173 doi:10.1001/jamapediatrics.2017.4173]

===2016: Comments RE: [http://tobaccoanalysis.blogspot.com/2016/06/new-pediatrics-study-provides.html E-Cigarettes and Future Cigarette Use] (#1)===
*The study counted anyone who had even puffed a cigarette once as being a smoker. So theoretically, a subject could have had a single puff of an e-cigarette and hated it, and then had a single puff of a cigarette and hated it, and they would be considered someone who initiated smoking because of vaping first. (Siegel)
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-e-cigarettes-and-future-cigarette-use/ E-Cigarettes and Future Cigarette Use] (#2)===
*Prof. Ann McNeill, Professor of Tobacco Addiction at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London : “The gateway hypothesis in the addictions field is frequently used but is highly contested as it has a poor evidence base in general. This study does nothing to strengthen that evidence base.”
*Prof. Peter Hajek, Director of the Tobacco Dependence Research Unit at Queen Mary University of London : "Like several previous studies of this type, this one just shows that people who try things, try things."
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://tobaccoanalysis.blogspot.com/2016/08/new-study-purports-to-show-that-e-cigs.html E-cigarette use is differentially related to smoking onset among lower risk adolescents ]===
*"To be clear, the rest of the story is that this new study provides no evidence that e-cigarettes are a gateway to smoking. Instead, it confirms that actual drug-related risk-taking behavior is a much better predictor of other drug-related risk-taking behavior than simply asking a kid if he thinks he will try another drug in the future or asking a kid how rebellious he is or how much his parents support him."
*"This second problem is that smoking initiation was measured by any experimentation with cigarettes, even if just a puff. So many of the youth in the sample may have puffed on a single e-cigarette at baseline and then puffed on a single cigarette some time over the next year and that would be considered as providing evidence that e-cigarettes are a "gateway" to smoking." (Siegel)
*Referring to: Wills TA, Sargent JD, Gibbons FX, et al E-cigarette use is differentially related to smoking onset among lower risk adolescents [https://tobaccocontrol.bmj.com/content/26/5/534 Tobacco Control 2017;26:534-539].

===2026: Comments RE: Flavored Electronic Cigarette Use and Smoking Among Youth===
*"The problems are obvious to those with any experience in statistics; the paper suffers from recall bias, sampling bias, and drawing causal conclusions from a cross-sectional survey. One of those confounders would be troubling yet the paper contains all of them." ([https://www.acsh.org/news/2016/11/07/all-animals-arent-cows-all-tobacco-isnt-cigarettes-and-surveys-arent-science-10412 Campbell])
*"This is a great example of the widespread bias against e-cigarettes that has taken hold in the tobacco control movement. Instead of presenting the study as showing equivocal results, the investigators and the American Academy of Pediatrics have both "chosen sides." This is not science; it is biased interpretation and presentation of science." ([https://tobaccoanalysis.blogspot.com/2016/11/investigators-botch-interpretation-of.html Siegel])
*Referring to: Hongying Dai, Jianqiang Hao; Flavored Electronic Cigarette Use and Smoking Among Youth. Pediatrics December 2016; 138 (6): e20162513. 10.1542/peds.2016-2513

===2014: Comments RE: [https://tobaccoanalysis.blogspot.com/2014/08/politicians-lie-to-public-about.html Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study]===
*"In a press release issued Monday by 13 members of Congress, a group of politicians claimed that there is "more" evidence that electronic cigarettes are a gateway to smoking...The reference which supports this assertion is a study by Dutra and Glantz which purports to provide data showing that electronic cigarettes are aggravating the tobacco epidemic among youth...The authors of this study make one of the most cardinal errors in all of epidemiology. They ignore the principle that correlation does not equal causation." (Siegel)
*Referring to: Dutra LM, Glantz SA. Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study. JAMA Pediatr. 2014 Jul;168(7):610-7. [http://doi:%2010.1001/jamapediatrics.2013.5488 doi: 10.1001/jamapediatrics.2013.5488]. Erratum in: JAMA Pediatr. 2014 Jul;168(7):684. PMID: 24604023; PMCID: PMC4142115.

==HPHC - Harmful and Potentially Harmful Constituents==

===2024: Comments RE: [https://www.pubpeer.com/publications/2D5B14D827614B6D4EFC821DCD2715 In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting]===
*"As a summary: the study by Beard et al [1] was conducted under such unrealistic conditions that its results (including its cytotoxic analysis) have little relevance to consumers and regulators." (Soulet, Sussman)
*Referring to: Beard JM, Collom C, Liu JY, Obiako P, Strongin RM, Zavala J, Sayes CM. In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting. Toxicology. 2024 Jun 13;506:153865. doi: 10.1016/j.tox.2024.153865. Epub ahead of print. PMID: 38876198.

===2024: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-observational-study-of-lead-and-uranium-levels-in-urine-of-teen-vapers/ Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring]===
*"More important, to me as a statistician at least, is that this research can’t establish that the higher levels of lead and uranium in the urine of participants who said they vaped more often were actually caused by their vaping." (McConway)
*"No control group (i.e., adolescents without any e-cigarette use) was included in the analysis...This study therefore cannot tell us anything about absolute increase in exposure to heavy metals from e-cigarette use in this population, only about relative exposure among less and more frequent e-cigarette users." (Shahab)
*See Also: [https://pubpeer.com/publications/E1834A07BDF105C94CC44DD0815856 PubPeer] "The reported mean values are then consistently far below the limit of detection. To draw any conclusions from values below LOD, is bad practice at best."
*Referring to: Kochvar A, Hao G, Dai HD Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring Tobacco Control Published Online First: 29 April 2024. doi: 10.1136/tc-2023-058554

===2023: Comments RE: [https://pubpeer.com/publications/F7311DC3982D9CD03C060190C9CFCB Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study]===
*The article has several serious shortcomings
**REPRODUCIBILITY AND LACK OF CRUCIAL INFORMATION.
**INAPPROPRIATE AIRFLOW FOR SUB-OHM DEVICES.
**ERRONEOUS CONCENTRATION VALUES
**STORAGE (Sussman)
*Referring to: Tehrani MW, Ahererra AD, Tanda S, Chen R, Borole A, Goessler W, Rule AM. Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study. Journal of Environmental Exposure Assessment. 2023; 2(2): 9. http://dx.doi.org/10.20517/jeea.2023.03

===2022: Comments RE: [https://pubpeer.com/publications/C4BE0346C79DAAC7E1BB2DD6B6FAA3#1 Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence]===
*The reader may find the following commentary on Uguna & Snape by Chris Snowdon of interest. It includes a scientific review of the paper by Roberto Sussman that provides a convincing rebuttal of the author's assertions that heated tobacco products generate smoke. (Bates)
*Referring to: Uguna CN, Snape CE. Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence. ACS Omega. 2022 Jun 22;7(26):22111-22124. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260752/ doi: 10.1021/acsomega.2c01527]. PMID: 35811880; PMCID: PMC9260752.

===2022: Comments RE: [https://pubpeer.com/publications/CF1D17EA015361EED28A7886C21CC1#1 Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors]===
*"Conclusion. This study might be a correct and rigorous examination of various processes of the particulate phase of e-cigarette aerosol that are strictly valid under the abnormal overheating testing conditions. The study does not prove that such processes can occur in low powered devices, or even in high powered devices under the recommended power ranges and airflow rates normally used by consumers. The utility to assess the safety profile of e-cigarettes requires the devices to be tested under the best approximation possible to realistic usage. Unfortunately, this study failed to comply with this important consistency condition." (Sussman)
*Referring to: Dada O, Castillo K, Hogan M, Chalbot MG, Kavouras IG. Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors. Sci Rep. 2022 Nov 3;12(1):18571. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633786/ doi: 10.1038/s41598-022-21798-w]. PMID: 36329089; PMCID: PMC9633786.

===2017: Comments RE: [https://pubpeer.com/publications/6E2711F55673ADF831D636E2D701B9 "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions]===
*Multiple Comments
**"Users will operate the equipment in a way that does not lead to harsh dry puff conditions, with associated high VA formation. This is a key human control feedback that does not exist in laboratory equipment. So experiments that just standardise power settings or volume consumption must take care to validate these are realistic proxies for human use for a particular device. In this paper, many of the coil, power and volume settings combinations were not realistic. That could have been avoided through engaging with people with real practical expertise." (Bates)
**"In reality, as power to the coil increases, liquid consumption also increases. In real-world scenarios, human users regulate both power and liquid flow to minimise the risk of dry-puff conditions and therefore avoiding increases in VA emissions." (Barnes)
*Referring to: Soha Talih, Rola Salman, Nareg Karaoghlanian, Ahmad El-Hellani, Najat Saliba, Thomas Eissenberg, and Alan Shihadeh Chemical Research in Toxicology 2017 30 (10), 1791-1793 [https://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00212 DOI: 10.1021/acs.chemrestox.7b00212]

===2017: Comments RE: [https://pubpeer.com/publications/E5B66481CC847E532FEDB066434E92 Hidden formaldehyde in e-cigarette aerosols]===
*"The problem for the authors is that cancer is a human condition and their calculation is based exposures measured by a lab machine in conditions that no humans would be able to tolerate." (Bates)
*See also: [https://pubpeer.com/publications/5D8FB0EB72850380D1A37DAA2097D6 PubPeer 2015-2017]
**"Although Jensen et al. mentioned in the 2015 NEJM research letter that the health risks of formaldehyde hemiacetal inhalation are unknown ("How formaldehyde-releasing agents behave in the respiratory tract is unknown..."), they made a calculation that the formaldehyde-attributable cancer risk from e-cigarette use is 5 to 15 times higher than from long-term smoking. These two statements are clearly contradictory, and the calculation of any cancer risk from formaldehyde hemiacetal emissions is invalid since no such risk has been established for these compounds." (Farsalinos)
*See also: [https://pubmed.ncbi.nlm.nih.gov/28864295/ replication study]
**"The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided." (Farsalinos, Voudris, Spyrou, Poulas)
*See also 2015: [https://retractionwatch.com/2015/09/11/researchers-call-for-retraction-of-nejm-paper-showing-dangers-of-e-cigarettes/ Researchers call for retraction of NEJM paper showing dangers of e-cigarettes]
**Links to the efforts to have the referenced paper retracted.
*Referring to: Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. [https://www.nejm.org/doi/full/10.1056/nejmc1413069 doi: 10.1056/NEJMc1413069]. PMID: 25607446.

==Marketing / Social Media==

===2019: Comments RE: [https://www.juullabs.com/study-highlights-influence-of-illegal-compatible-products/ Characterising JUUL-related posts on Instagram]===
*A recent study in Tobacco Control relating to an analysis of “JUUL-related” Instagram posts contains serious factual errors and mischaracterizations of JUUL Labs’ historical social-media activity, falsely tying the company to the activities of manufacturers of “JUUL compatible” products that we believe are illegally on the market. (JUUL)
* [https://pubpeer.com/publications/B1DD80F0C868A59D609F0B9699E5F9 Additional comments]: In fact, a completely different story emerges from the data as qualified by Juul's statement. This is that FDA's failure to control newly-introduced Juul look-a-likes (which are illegal if introduced after 8 August 2016) is spawning a lawless industry driven by social media and in conflict with Juul's efforts to control sales of its products to youth. The study does not interrogate the underlying reality and I think Juul is right to react strongly. (Bates)
**Referring to: Czaplicki L, Kostygina G, Kim Y, Perks SN, Szczypka G, Emery SL, Vallone D, Hair EC. Characterising JUUL-related posts on Instagram. Tob Control. 2020 Nov;29(6):612-617. Epub 2019 Jul 2. PMID: 31266903. [https://doi.org/10.1136/tobaccocontrol-2018-054824 doi: 10.1136/tobaccocontrol-2018-054824]

==Multiple Outcomes==

===2024: Comments RE: [https://www.ecigarette-research.org/research/index.php/research/2024/281-ecig-disease Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===
*"The study provides zero evidence on any risk associated with e-cigarette use, whether absolute risk or in comparison with smoking. The question that was supposed to be addressed in this metanalysis CANNOT be examined with the studies included in their analysis." (Farsalinos)
*[https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 See Also]: "The methods look impressive, but the devil is in the dirty details buried in the nearly 100 pages supplemental material. The authors have done an admirable job collecting studies and organizing them, but the conclusions reached are untenable, and unsupportable at least for now." (Cummings)
**Referring to: Glantz SA, Nguyen N, Oliveira da Silva AL. Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes. NEJM Evid. 2024 Mar;3(3):EVIDoa2300229. Epub 2024 Feb 27. PMID: 38411454. [https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300229 doi: 10.1056/EVIDoa2300229]

===2024: Comments RE: [https://tobaccocontrol.bmj.com/content/33/3/373.responses#-comments-on-paper-by-asfar-et-al-%E2%80%9Crisk-and-safety-profile-of-electronic-nicotine-delivery-systems-ends-an-umbrella-review-to-inform-ends-health-communication-strategies%E2%80%9D Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies]===
*"Communicating health risk information about ENDS has to have some context to be meaningful to consumers. A common misconception about tobacco use is that the most dangerous component of the product is nicotine. However, while nicotine can be addictive, it is the other toxicants in tobacco, especially burned tobacco, that are the true culprits of tobacco-related diseases. Thus, when communicating information about the health risks of tobacco products, it makes sense to provide consumers with information about the relative health dangers from burned compared to unburned tobacco products. The example risk messages included in the supplementary materials to the paper appear to be developed with a goal of discouraging anyone from using a vaping product rather than to inform potential users about risks." (Cummings, Smith, Schroeder, Warner, McNeill, Hartmann-Boyce, Levy)
**Referring to: Asfar T, Jebai R, Li W, Oluwole OJ, Ferdous T, Gautam P, Schmidt M, Noar SM, Lindblom EN, Eissenberg T, Bursac Z, Vallone D, Maziak W. Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies. Tob Control. 2022 Sep 8:tobaccocontrol-2022-057495. doi: [https://tobaccocontrol.bmj.com/content/33/3/373 10.1136/tc-2022-057495]. Epub ahead of print. PMID: 36252567; PMCID: PMC10043882.

===2022: Comments RE: [https://colinmendelsohn.com.au/wp-content/uploads/2022/07/Mendelsohn-Wodak-Hall-Borland.-A-critical-analysis-of-Ecigs-and-health-outcomes-systematic-review-of-global-evidence.-DAR-2022.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]===
*Contrary to the conclusions of the Banks review, the evidence suggests that vaping nicotine is an effective smoking cessation aid; that vaping is substantially less harmful than smoking tobacco; that vaping is diverting young people away from smoking; and that vaping by smokers is likely to have a major net public health benefit if widely available to adult Australian smokers. (Mendelsohn)
**Referring to: Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. [https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022.

===2022: Comments RE: [https://pubpeer.com/publications/727EA7B64FB27270F20717729D7629 Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice]===
*Although this new research from Moshensky et al., does add to the scientific literature about previously marketed JUUL products, we believe the conclusions presented in the manuscript are not adequately supported by the study data. In addition, the lack of quantitative data on actual dosing limits the ability to establish relevance to potential human exposures from product use. Furthermore, the lack of a comparison against the effects of tobacco smoke limits the ability to evaluate these study findings in the context of the tobacco product risk continuum, and risk relative to use of combusted cigarettes. (Weil)
**Referring to: Moshensky A, Brand CS, Alhaddad H, Shin J, Masso-Silva JA, Advani I, Gunge D, Sharma A, Mehta S, Jahan A, Nilaad S, Olay J, Gu W, Simonson T, Almarghalani D, Pham J, Perera S, Park K, Al-Kolla R, Moon H, Das S, Byun MK, Shah Z, Sari Y, Heller Brown J, Crotty Alexander LE. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife. 2022 Apr 12;11:e67621. PMID: 35411847; PMCID: PMC9005188. [https://doi.org/10.7554/elife.67621 doi: 10.7554/eLife.67621]

===2018: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-modelling-study-on-electronic-cigarettes-in-the-us/ Quantifying population-level health benefits and harms of e-cigarette use in the United States]===
*"The authors make some very speculative assumptions here, particularly on the ‘gateway’ effect in teenagers – they assume that vaping leads to smoking. The trouble is, all their data on this comes from studies that don’t prove anything of the sort...The authors’ estimate of ‘life years lost’ is primarily driven by their overestimate of e-cig use contributing to a significant increase in the uptake of smoking in kids." (Shahab)
*"This new ‘finding’ is based on the bizarre assumption that for every one smoker who uses e-cigs to quit, 80 non-smokers will try e-cigs and take up smoking. It flies in the face of available evidence but it is also mathematically impossible." (Hajek)
**Referring to: Soneji SS, Sung HY, Primack BA, Pierce JP, Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS One. 2018 Mar 14;13(3):e0193328. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193328 doi: 10.1371/journal.pone.0193328]. PMID: 29538396; PMCID: PMC5851558.

==Respiratory==
*To learn more about Popcorn Lung, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Vaping_causes_Popcorn_Lung Myth: Vaping causes Popcorn Lung]

===2023: Comments RE: [https://pubpeer.com/publications/035039E269389CBFC88FCB9AFD225C#8 E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring]===
*Given all these shortcomings (opaqueness, unrealistic airflow and nicotine, likely overexposure of mice), the results of this study are not reliable to assess potential harms from exposure to e-cigarette aerosol. (Sussman)
*Referring to: Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, Miller RA, Wold LE, Gorr MW. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L676-L682. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722245/ doi: 10.1152/ajplung.00233.2022]. Epub 2022 Oct 11. PMID: 36218276; PMCID: PMC9722245.

===2022: Comments RE: [https://pubpeer.com/publications/D93498039BF8D05DFAE58BFC29DD1B The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Therefore, it is deficient and unreliable." (Rodu)
*Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019 Oct 16;19(1):180. [https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0950-3 doi: 10.1186/s12890-019-0950-3]. PMID: 31619218; PMCID: PMC6796489.

===2022: Comments RE: [https://pubpeer.com/publications/075B90E6B4FEB1AF3BB188690C317F Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017]===
*"The study by Osei et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Osei, A. D., Mirbolouk, M., Orimoloye, O. A., Dzaye, O., Uddin, S. M. I., Benjamin, E. J., Hall, M.E., DeFilippis, A.P., Bhatnagar, A., Biswal, S.S., Blaha, M. J. (2020). Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017. American Journal of Preventive Medicine. [https://www.ajpmonline.org/article/S0749-3797(19)30479-9/fulltext https://doi.org/10.1016/j.amepre.2019.10.014]

===2022: Comments RE: [https://pubpeer.com/publications/8993443E1BA20DF0D8F4E1F51DFB79 Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data]===
*"The study by Wills et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Wills TA, Choi K, Pokhrel P, Pagano I. Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data. Prev Med. 2022 Aug;161:107137. [https://www.sciencedirect.com/science/article/abs/pii/S0091743522001864 doi: 10.1016/j.ypmed.2022.107137]. Epub 2022 Jul 9. PMID: 35820496; PMCID: PMC9328844.

===2022: Comments RE: [https://pubpeer.com/publications/7B80EB6A718B6A0F2B4634DFE56886 E-cigarette use and respiratory disorder in an adult sample]===
*"Their study used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
*Referring to: Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019 Jan 1;194:363-370. [https://www.sciencedirect.com/science/article/abs/pii/S0376871618307622 doi: 10.1016/j.drugalcdep.2018.10.004]. Epub 2018 Nov 7. PMID: 30472577; PMCID: PMC6312492.

===2022: Comments RE: [https://pubpeer.com/publications/9946B2A97F6F6AF0F898D95F7CB23D E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report]===
*"The problem with these studies is disentangling the effects of a smoking career (something more complicated than adjusting for current-, former-, never-smoking status) and subsequent vaping behaviour. Also, the relationships are complicated by reverse causation (was the vaping a response to smoking-induced respiratory symptoms?), a hard-to-define counterfactual (has the vaping displaced smoking or displaced abstinence?), and the fact that respiratory damage arises from cumulative exposure and vaping exposures may be adding incremental risk (would the subject have any symptoms if they hadn't smoked first?)." (Bates)
*Referring to: Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 Dec 1;17(12):e0269760. [https://pubmed.ncbi.nlm.nih.gov/36454742/ doi: 10.1371/journal.pone.0269760]. PMID: 36454742; PMCID: PMC9714717.

===2020: Comments RE: [https://pubpeer.com/publications/EF05B531214379DD314797A20F2D9D Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?]===
*"The problem is that vegetable glycerin (glycerol) is not a lipid it is an alcohol. It cannot cause the lipoid pneumonia symptoms mentioned." (Bates)
*"Endogenous lipoid pneumonia from VG (or PG) inhalation is a speculation and implausible...The experience in the US over the past several months clearly shows that the culprit for the acute lung intoxication cases are black market THC oils which were sold as THC oils, not e-cigarette products." (Farsalinos)
*"visual assessment of lung HRCT scans showed no pathological findings in people vaping daily for more than 3.5 years. In particular, no CT features compatible with early signs of COPD (i.e. parenchymal micronodules, ground-glass opacity, or macroscopic emphysema) or lipoid pneumonia or popcorn lung disease were present." (Polosa)
*Referring to: Eissenberg T, Maziak W. Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury? Am J Respir Crit Care Med. 2020 Apr 15;201(8):1012-1013. [https://pubmed.ncbi.nlm.nih.gov/31917600/ doi: 10.1164/rccm.201910-2082LE]. PMID: 31917600; PMCID: PMC7159422.

===2019-2020: Comments RE: [https://pubpeer.com/publications/7571819CEB7A2BC425BE3D7061410D Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis]===
*Multiple Comments:
**"One of the essential criteria of causal inference is that exposure to the cause precedes disease onset. Three of the diseases Glantz studies — COPD, chronic bronchitis and emphysema — take decades to become clinically apparent and would have been present, even though undiagnosed, in many of his cases long before his study began in 2014, and indeed even before e-cigarettes first became available in the US in about 2007. His findings are also flawed by the fact that most vapers have smoked, and since smoking is a strong cause of chronic lung disease, vapers inevitably carry an increased risk of lung disease long after quitting smoking. Glantz claims to have allowed for this statistically but his approach is simplistic: he lacks the detail of lifetime duration and intensity of smoking required. On these grounds alone his conclusion is specious." (Britton)
**"Donald Kenkel and colleagues at Cornell University conducted a replication of the analysis using econometric techniques...When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco." (Bates)
*Referring to: Bhatta DN, Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020 Feb;58(2):182-190. [https://www.ajpmonline.org/article/S0749-3797(19)30391-5/fulltext doi: 10.1016/j.amepre.2019.07.028]. Epub 2019 Dec 16. PMID: 31859175; PMCID: PMC6981012.

===2019: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-ecig-vapour-and-cancer-in-mice/ Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice]===
*Multiple comments:
**“The comparison between mice breathing vapour and mice breathing air is not statistically significant. There is no sample size justification and no power calculation. There is no message to the public here – I suspect these results are just noise.” (Britton)
**“The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures. The authors assigned the effects they observed to a carcinogen NNK – but NNK has been measured before in human vapers, and it is known that exposure from vaping is either negligible or none.” (Hajek)
*Referring to: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. [https://pubmed.ncbi.nlm.nih.gov/31591243/ doi: 10.1073/pnas.1911321116]. Epub 2019 Oct 7. Erratum in: Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22884. PMID: 31591243; PMCID: PMC6815158.

===2017: Comments RE: [https://pubpeer.com/publications/41F6EA57D0803EEE9DF65162DF0097 Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts]===
*"It is literally true that they "find no evidence...", but that is because this study is completely ill-suited to drawing any policy conclusions about e-cigarettes and COPD. Despite hinting at the limitations of cross-sectional data, the authors draw a negative-sounding conclusion without addressing the key question of how respiratory health changes for a given smoker who uses e-cigarettes to quit or cut down once they are ill from smoking or as a way of preventing COPD." (Bates)
*Referring to: Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. [https://pubmed.ncbi.nlm.nih.gov/28884423/ doi: 10.1007/s11606-017-4150-7]. Epub 2017 Sep 7. PMID: 28884423; PMCID: PMC5698219.

===2016: "Popcorn Lung" Comments RE: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892932/ Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes”]===
**"Over the past five years, we have published the results of several studies in which diacetyl and 2,3-pentanedione levels were measured in various consumer products..."
**"..."hundreds of consumer products (e.g., tea, coffee, citrus juices, butter) contain naturally occurring diacetyl and 2,3-pentanedione...several studies have shown that airborne diketones associated with these products are easily detectable..."
**"Unless one assumes that unflavored coffee beans pose a serious risk of “popcorn lung,” a rare and oftentimes lethal disease, then one should agree that exposures to airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk."
**"Similarly, we measured concentrations of naturally occurring diacetyl and 2,3-pentanedione in mainstream cigarette smoke at levels (200–400 ppm and 30–50 ppm, respectively) that are hundreds of thousands of times higher than the NIOSH and ACGIH OELs, yet cigarette smoking is not associated with “popcorn lung”. Also, as others have noted, diketone exposures from traditional cigarettes are higher than those associated with e-cigarette use, hence switching from tobacco to e-cigarettes may result in reduced diketone exposure."
**"Ironically, suggesting that diketone levels in e-cigarettes are potentially dangerous could actually lead to higher diketone exposures in the smoking population if smokers decide not to switch to e-cigarettes due to as yet unfounded health concerns." (Pierce, Abelmann, Finley) For further information, see authors [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892901/ response] to the comments above.
*See Also: 2016: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892907/ On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings]
**"The 51 e-juices sampled make up a very small proportion of all the products sold, and there is variability in the chemical content of specific products as well as how those chemicals are delivered by different devices. The authors therefore acknowledge that it is impossible to extrapolate their results to all the other products on the market. Importantly, this study did not assess levels of diacetyl, 2,3-pentanedione, and acetoin in actual users, much less health effects. So it’s premature to assume that exposure to these chemicals via e-cigarettes causes health problems." (Arnold)
*See Also: 2015: [https://rodutobaccotruth.blogspot.com/2015/12/is-harvard-e-cigarette-buttery-flavor.html Is the Harvard E-Cigarette Buttery Flavor Study Credible?]
**"As I advised previously, vapers should only use liquids that are certified to be free of buttery flavors that are suspected respiratory toxicants. However, laboratory investigations of e-cigarettes should use validated methods to assure credibility. The results of the Harvard Buttery Flavor Study do not meet this standard." (Rodu)
*See Also: 2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/236-da2 A new study finds diacetyl in e-cigarettes but exaggerates risks and fails to discuss about smoking]
**"In conclusion, the article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes. They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk." (Farsalinos)
*See Also: 2015: [https://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking]
**"Nevertheless, it is disingenuous and actually damaging to the public's health to spread the message that vaping causes fatal lung disease or even that it appears to increase the risk for popcorn lung. And it is especially disingenuous and damaging to send these messages to the public without telling us that smoking produces exposure to diacetyl that is on average about 750 times higher than vaping." (Siegel)
*Referring to: Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 2016 Jun;124(6):733-9. [https://pubmed.ncbi.nlm.nih.gov/26642857/ doi: 10.1289/ehp.1510185]. Epub 2015 Dec 8. PMID: 26642857; PMCID: PMC4892929.

===2016: Comments RE: [https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===
*"The mice were severely overdosed with nicotine, up to the lethal levels for mice, and a huge amount above what any human vaper would get...Regarding the relevance to human health, nicotine poisoning poses normally no risk to vapers or smokers because if nicotine concentrations start to rise above their usual moderate levels, there is an advance warning in the form of nausea which makes people stop nicotine intake long before any dangerous levels can accrue. (Mice in these types of experiments do not have that option)." (Hajek)
*Referring to: Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax. 2016 Dec;71(12):1119-1129. [https://pubmed.ncbi.nlm.nih.gov/27558745/ doi: 10.1136/thoraxjnl-2015-208039]. Epub 2016 Aug 24. PMID: 27558745; PMCID: PMC5136722.

===2015: Comments RE: [https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/5dfe1e98-3100-4102-a425-a647b9459456 Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model]===
*" In other words, to obtain the same exposure in humans the e-cig user should take 11000 – 13000 puffs per day. Assuming 8 hours of sleep per day, in order to acquire such a high number of puffs e-cig users would need to take 11-13 puffs per minute and thus practically take an e-cig puff with each breath. In conclusion we recommend that the results of the discussed study should be interpreted with caution and that more studies with more realistic levels of e-liquid exposure should be conducted." (Mukhin, Rose)
*Referring to: Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. (2015) Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. PLoS ONE 10(2): e0116861. https://doi.org/10.1371/journal.pone.0116861

=Retractions by Journal=

===2025: Comments RE: [https://academic.oup.com/ntr/article/28/2/314/8320356 Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review]===
*Therefore, the Editor is retracting this article because the article was accepted with an undisclosed conflict of interest that would have changed the editorial decision.
**Referring to: Xingyu Liu, Rana Tayyarah, Xiang Chang, Xin Gao, Lisha Chen, Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review, Nicotine & Tobacco Research, 2025; ntaf189, https://doi.org/10.1093/ntr/ntaf189.

===2024: Comments RE: [https://www.science.org/content/article/questionable-firms-tempt-young-doctors-with-easy-publications Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES]===
*"The more they looked at the article, the more problems they saw. The work was based on data from an annual survey on health and nutrition by the U.S. Centers for Disease Control and Prevention (CDC), but the reported number of survey respondents was inexplicably off by an order of magnitude—the survey is completed by about 5000 people a year, but the paper cited 266,058 respondents from 2015 to 2018. The authors also failed to report whether the difference in age of stroke onset between vapers and traditional smokers could simply be due to vapers being younger overall. And those were just a few of the obvious issues, according to Cohen and Foxon, who alerted both the authors and the journal to their concerns." (Joelving)
*See Also: [https://twitter.com/FloeFoxon/status/1786522387338465755 Tweetorial] (Foxon) and [https://pubpeer.com/publications/1F118DC9A92A4FC13507BB5448462D PubPeer] (Richardson and others - 4 comments)
*Retracted: 18th of December, 2025
**Referring to: Patel U, Patel N, Khurana M, Parulekar A, Patel A, Ortiz JF, Patel R, Urhoghide E, Mistry A, Bhriguvanshi A, et al. Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES. Neurology International. 2022; 14(2):441-452. https://doi.org/10.3390/neurolint14020037

===2022: Original: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239491/ Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study]===
*Citation: RC, Dawoodi S, Fabara SP, Asad M, Khayyat A, Chandramohan S, Aslam A, Unachukwu N, Nasyrlaeva B, Jaiswal R, Chowdary SB, Malik P, Rabbani R. Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study. Gastroenterology Res. 2022 Jun;15(3):113-119. doi: 10.14740/gr1490. Epub 2022 Jun 22. Retraction in: Gastroenterology Res. 2023 Jun;16(3):201. PMID: 35836707; PMCID: PMC9239491.
*2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284643/ Retraction Notice to “Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study”]
**Media - Filter: [https://filtermag.org/vaping-liver-disease-study-retracted/ Journal Retracts Study That Linked Vaping to Liver Disease]

===2022: Original: [https://reason.com/wp-content/uploads/2023/01/1438-9260-6-PB.pdf Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study]===
*Citation: Chidharla A, Agarwal K, Abdelwahed S, Bhandari R, Singh A, Rabbani R, Patel K, Singh P, Mehta D, Manaktala PS, Pillai S, Gupta S, Koritala T. Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study. World J Oncol. 2022 Feb;13(1):20-26. doi: 10.14740/wjon1438. Epub 2022 Feb 8. Retraction in: World J Oncol. 2022 Dec;13(6):417. PMID: 35317331; PMCID: PMC8913014.
*2022: [https://reason.com/wp-content/uploads/2023/01/1562-10357-1-PB.pdf Retraction Notice to “Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study”]
**Media - Reason: [https://reason.com/2023/01/04/a-medical-journal-retracts-a-2022-study-that-linked-vaping-to-cancer/ A Medical Journal Retracts a 2022 Study That Linked Vaping to Cancer]

===2019: Original: [https://www.ahajournals.org/doi/10.1161/JAHA.119.012317 Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]===
**Citation: Bhatta DN, Glantz SA. Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health. J Am Heart Assoc. 2019 Jun 18;8(12):e012317. doi: 10.1161/JAHA.119.012317. Epub 2019 Jun 5. Retraction in: J Am Heart Assoc. 2020 Feb 18;9(4):e014519. Erratum in: J Am Heart Assoc. 2019 Nov 5;8(21):e002313. PMID: 31165662; PMCID: PMC6645634.
*2020: [https://www.ahajournals.org/doi/10.1161/JAHA.119.014519 Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]
**[https://pubpeer.com/publications/F177153E02CA8B3E7B9E70BC8DB204 PubPeer]
**Media - USA Today: [https://www.usatoday.com/story/news/health/2020/02/20/nyu-scientists-others-call-taxpayer-funded-ucsf-vaping-study-probe/4805323002/ A study claimed vaping doubles risk for heart attacks. It's been retracted for being 'unreliable']

===2019: Original: [https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.29148 Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non–small cell lung cancer]===
**Citation: Liu Z, Lu C, Zhao G, Han X, Dong K, Wang C, Guan JZ, Wang Z. Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non-small cell lung cancer. J Cell Biochem. 2019 Oct;120(10):18370-18377. doi: 10.1002/jcb.29148. Epub 2019 Jun 12. Retraction in: J Cell Biochem. 2024 Apr 5. doi: 10.1002/jcb.30562. PMID: 31190333.
*[https://pubmed.ncbi.nlm.nih.gov/38577886/ PubMed Retraction]
*Retracted 2024: [https://pubpeer.com/publications/D500DE74010B291A7B27CBB9083FEA PubPeer Comment about retraction]

=Retractions by Author Request=

===2025: [https://link.springer.com/article/10.1038/s41388-024-03269-w Retraction Note: Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis]===
"The authors have retracted this article. After publication, concerns were raised regarding highly similar ex vivo brain images in Figs. 2A (Vehicle, right), 5A (miR-4466 inh., left) and 6E (-Nic.+Stat3i, right). The authors thoroughly checked the underlying data and found that the data were mismanaged, which may have affected the presented results.
**Citation: Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R, Singh R, Li W, Topaloglu U, Ruiz J, Watabe K. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022 May;41(22):3079-3092. doi: 10.1038/s41388-022-02322-w. Epub 2022 Apr 23. Retraction in: Oncogene. 2025 Jan 9. doi: 10.1038/s41388-024-03269-w. PMID: 35461327; PMCID: PMC9135627.

===2024: [https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00998-w The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis]===
**Citation: Tehrani, H., Rajabi, A., Ghelichi- Ghojogh, M. et al. RETRACTED ARTICLE: The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis. Arch Public Health 80, 240 (2022). https://doi.org/10.1186/s13690-022-00998-w
*[https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-024-01345-x Retraction Notice]: The authors have retracted this article because it incorrectly reports the results of several studies included in their review. This impacts the overall results of their meta-analysis. The authors have been offered the opportunity to re-analyse their findings and to submit an updated version to the journal, which will be subjected to robust peer review.

===2024: [https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814489 RETRACTED: Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking A Randomized Clinical Trial]===
**Citation: Liu Z. Notice of Retraction: Lin HX et al. Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. 2024 May 1;184(5):589. doi: 10.1001/jamainternmed.2024.1125. PMID: 38551593.
*[https://pubpeer.com/publications/A3736116C180E920966659A2AEA32F Author's retraction request post on PubPeer]
*Retraction Watch: [https://retractionwatch.com/2024/04/02/paper-claiming-vaping-tops-nicotine-gum-for-smoking-cessation-retracted-from-jama-journal/ Paper claiming vaping tops nicotine gum for smoking cessation retracted from JAMA journal]

=Suggestions to add to this page=

===2026: [https://www.sciencedirect.com/science/article/pii/S2213538325000591 RETRACTED: Evidence on vaping e-cigarettes as a risk factor for cancer: A systematic review]===

===2026: [https://pubmed.ncbi.nlm.nih.gov/42010224/ Retraction Note: Alleviation of nicotine-induced reproductive disorder, clastogenicity, and histopathological alterations by fenugreek saponin bulk and nanoparticles in male rats]===
*[https://pubmed.ncbi.nlm.nih.gov/35182342/ Paper]
*[https://pubpeer.com/publications/8390CD448F7A458E580486AF466E27 PubPeer]

===2025: [https://pmc.ncbi.nlm.nih.gov/articles/PMC12708306/ Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey]===

===2024: [https://www.sciencemediacentre.org/expert-reaction-to-epigenetic-changes-in-cells-of-smokers-and-vapers/ expert reaction to epigenetic changes in cells of smokers and vapers]===

===2024: [https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===

===2022: [https://link.springer.com/article/10.1007/s11739-022-03163-x A tale of flawed e-cigarette research undetected by defective peer review process]===
*[https://www.coehar.org/anti-vaping-narrative-driven-by-low-quality-science-goes-undetected-by-editorial-quality-checks/ Anti-vaping narrative driven by low quality science goes undetected by editorial quality checks]

===2022: [https://www.mdpi.com/2305-6304/10/12/714 Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===

===2025: [https://www.nature.com/articles/s41467-025-59975-w Retraction Note: Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung]===
*"The authors have retracted this article. After publication, concerns were raised regarding highly similar images in the figures, specifically..."

===2025: RE [https://www.amjmed.com/article/S0002-9343(24)00796-4/fulltext Scientific Inaccuracies in Smoking Cessation Guidance]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===

===2025: RE [https://www.pubpeer.com/publications/B604AE5B635D7A1A0E0A6571FDEF16 Exposure to third hand e-cigarette vapour impairs cognitive function in young mice]===

===2025: [https://www.qeios.com/read/FDX7P3 Exposure to Benzene, Toluene, and Xylenes from Electronic Cigarette Use Compared to Working Environment Permissible Exposure Limits: A Risk Assessment Analysis of a Recent Publication]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntae232/7780360?login=false Electronic cigarettes during pregnancy: Another tool for discontinuing smoking?]===
*note: this isn't formatted for placement in the correct section
*[https://x.com/ArielleSelya/status/1839786888099463656 Twitter thread]

===2025: [https://www.qeios.com/read/9XT2GU Critical Appraisal of Exposure Studies on E-Cigarette Aerosols Generated by High-Powered Devices]===
*note: this isn't formatted for placement in the correct section

===[https://pubmed.ncbi.nlm.nih.gov/31712273/ Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes]===
*note: this isn't formatted for placement in the correct section
*[https://www.sciencemediacentre.org/expert-reaction-to-case-study-linking-lung-inflammation-to-vaping-in-a-16-year-old/ Expert Comments]

===Paper: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00253 Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]===
*Comment: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00367 Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]
*Response: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00414 Response to Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]

===Paper: [https://gh.bmj.com/content/9/2/e013866 Pharmaceuticalisation as the tobacco industry’s endgame]===
*Comment: [https://pubpeer.com/publications/374B1C6D333BD84814E878DF9D1611 Title: Errors in one sentence - oversights or indicators of other problems?]

===[https://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/233-pm A new study reports that e-cigarettes emit toxins to the environment but the authors did not really find any…]===

 

[[File:Retracted 2.png|center|]]
[[Category:Studies, Surveys, and Papers]]

Nicotine - Stigma

2026-04-06T09:17:48Z

Skip: /* 2018: Substance use, recovery, and linguistics: The impact of word choice on explicit and implicit bias */

[[File:Support Not Stigma smokers.png|center|]]
 
 

<big>'''Stigma and stigmatizing language lead to viewing people as less worthy and can lead to bias and [https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addiction discrimination]. Stigma can affect the mental health of the stigmatized, may inhibit their ability to achieve wanted changes in their lives, and may cause them to avoid [https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-language-showing-compassion-care-women-infants-families-communities-impacted-substance-use-disorder medical care] or helpful services. This page explores the use of Person-First Language and the consequences of stigmatizing people, with a focus on those who use nicotine.'''</big>
 
 

='''Smoking (Nicotine) Stigma and the use of "Smoker"'''=

=='''Publication Policies/Author Guidelines - Person-First Language (PFL)'''==

==='''Mentions "Smoker" '''===

====2021: ACS/ACS CAN: [https://www.cancer.org/content/dam/cancer-org/online-documents/en/pdf/flyers/health_equity_inclusive_language_writing_guide.pdf Inclusive Language and Writing Guide]====
*Terms to avoid: smokers/former smokers
**Suggested Replacement: people who smoke/used to smoke/ quit smoking
**Rationale: removes stigmatizing or shaming/blaming language and keeps people first

====[https://www.elsevier.com/__data/promis_misc/AJPM%20Revision%20Checklist.pdf ''American Journal of Preventative Medicine'']====
*2023 AJPM Revision Guide: "Person-first language is used throughout (“people who smoke” preferred instead of “smokers”; “persons who use drugs” preferred instead of “drug users”, etc.)."

====[https://www.chestcc.org/authinfo_prep ''Chest Critical Care'']====
*Avoid Lung cancer patient. Preferred Patient/person with lung cancer
*Avoid Smoker. Preferred Patient/person with active tobacco use OR patient/person who smokes
*Avoid Nicotine addict Preferred Patient/person with nicotine dependence
*Avoid Former smoker Preferred Patient/person with smoking history
*Avoid Nonsmoker Preferred Patient/person who doesn’t smoke

====John Hopkins Bloomberg School of Public Health: [https://publichealth.jhu.edu/offices-and-services/office-of-external-affairs/communications-and-marketing/bloomberg-school-editorial-style-guide Bloomberg School Editorial Style Guide]====
*To avoid stigmatizing language, do not use these terms:
**smoker(s)
**tobacco [or other acceptable product term] user(s)
**non-smoker(s)
**never smoker(s)
**vaper(s)
**user(s)
*Use person-first language:
**person who smokes/people who smoke
**person who uses tobacco/people who use tobacco [or other acceptable product term]
**people who report no current smoking
**people who use heated tobacco products
**He has never smoked.
**She uses e-cigarettes.

====[https://onlinelibrary.wiley.com/pb-assets/assets/15422011/JMWH%20Style%20Guide%20March-1680518218383.pdf ''Journal of Midwifery & Women’s Health'' (JMWH)]====
*Do not label people with their condition.
**Avoid: alcoholic, addict, user, abuser, smoker, asthmatic, epileptic, obese.
**Preferred: people with opioid use disorder, person who smokes, individuals who have asthma, people with epilepsy, person with obesity.
*An exception to this guidance is in cases where persons prefer to be identified by a condition.
**Example: Deaf person, pregnant person.

====''Journal of the National Comprehensive Cancer Network'' (JNCCN) [https://www.nccn.org/docs/default-source/about/nccn-guidance-on-inclusive-language.pdf?sfvrsn=53c8c78f%201 NCCN Language Guidance: Sensitive, Respectful, and Inclusive Language for NCCN Publications]====
*Patients should not be belittled or made to feel stigmatized by their age, their size, or their past or current behaviors.
*Individuals should not be defined by their substance use. Feeling stigma can prevent people with a substance use disorder from seeking treatment, and implicit or explicit bias of health care professionals can impact the care they provide to individuals with substance use disorders. NCCN publications use person-first language and avoid terms associated with stigma and negative bias when discussing substance use.
*Instead of "smokers," use "people who smoke."

====[https://www.jto.org/content/authorinfo ''Journal of Thoracic Oncology'']====
*End Stigma: For example, instead of “smoker,” use “person who smokes.”

====[https://www.jtocrr.org/content/authorinfo ''JTO Clinical and Research Reports'']====
*Use Person-First Language: For example, instead of “lung cancer patient,” use “patient/person with lung cancer.”
*End Stigma: For example, instead of “smoker,” use “person who smokes.”

====[https://pubs.rsna.org/page/radiology/blog/2023/2/ryblog_02222023 ''Radiology'']====
*Remember person-first language. Participant who currently smokes, not “smoker.”

====''Tobacco Control'': [https://tobaccocontrol.bmj.com/content/32/2/133 New policy of people-first language to replace ‘smoker’, ‘vaper’ ‘tobacco user’ and other behaviour-based labels]====
*..."Tobacco Control is instituting a new policy of people-first language when referring to people who use tobacco and related products. Terms such as ‘smoker’, ‘vaper’ and ‘tobacco user’ (and their various iterations) should no longer be used as general descriptors."
*"However, people-first language does not invalidate how people may choose to self-identify. It provides a broader conceptualisation which reduces the potential for stigma, resists tobacco industry narratives and promotes greater precision and accuracy, as well as creating space which recognises these self-claimed identities can change."

==='''Doesn't Mention "Smoker" (Person (people)-First, Person-Centered, Person-Forward)'''===

====[https://www.sciencedirect.com/journal/advances-in-nutrition/publish/guide-for-authors ''Advances in Nutrition'']====
*Strongly recommends the use of “people-first language.”

====[https://academic.oup.com/alcalc/pages/General_Instructions ''Alcohol and Alcoholism'']====
*“Words Matter” - Guidance on Language and Terminology
*Please use “person first” language (e.g. “person/patient/participant with alcohol use disorder”, rather than “alcoholic”). Person-first language helps to reduce stigma against people who use drugs by not implying that they are their disorder. “Addict” and “alcoholic,” while often used among some patients and the public, can be stigmatizing, dehumanizing, and do not reflect the very human condition of addiction.
*Preferred terms for the disease include substance use disorder, alcohol use disorder, drug use disorder, gambling disorder, and addiction. Use of terms in other diagnostic systems are acceptable provided the terms are used as defined. Examples include “dependence” when referring to pre-DSM 5 or International Classification of Diseases (ICD) diagnoses, or the ICD diagnosis “Harmful Use.” Note that “drug” should not be used when the more appropriate term is “substance” (i.e., drug, alcohol, and tobacco) or “medication” (i.e., drug intended for medical use).“Person who uses drugs” should be used rather than “drug user.”

====[https://www.atia.org/wp-content/uploads/2023/07/ATOB-Author-Guidelines_2023.docx ''Assistive Technology Outcomes and Benefits Journal'' (ATOB) ]====
*"Authors should use “person-first” language..."

====[https://journals.sagepub.com/doi/10.1177/1079063218783798 ''Association for the Treatment and Prevention of Sexual Abuse'' - ATSA]====
*Authors are encouraged to be thoughtful about the connotations of language used in their manuscripts to describe persons or groups. Person-first language (e.g., “persons with sexual offense histories”, “individual who has been adjudicated for…”, “child/adolescent with sexual behavior problems”) is generally preferred because it is often more accurate and less pejorative than terms like “sex offender”. Terms like “sex offender” imply an ongoing tendency to commit sex offenses, which is inaccurate for many persons who have been convicted for sex offenses given current sexual recidivism base rates. Similarly, the term suggests a homogeneous group defined and stigmatized on the basis of criminal behaviors that may have taken place infrequently or many years in the past.

====[https://academic.oup.com/cid/pages/Manuscript_Preparation ''Clinical Infectious Diseases'']====
*Authors should use inclusive and person-first language in manuscripts. Describe people as having a condition or disease, experiencing a circumstance, or doing something specific rather than the condition, disease, circumstance, or activity being part of their identity. For example, they should use “people with obesity,” “person with HIV,” “person who injects drugs,” and so forth, rather than “obese people” “HIV positive” or “drug user.”

====[https://c4disc.pubpub.org/guidelines-on-inclusive-language-and-images-in-scholarly-communication Coalition for Diversity and Inclusion in Scholarly Communications]====
*"In most cases it is preferable to emphasize the person over the attribute. For example, “person with cancer” instead of “cancer patient”, “man in prison” instead of “inmate.” Emphasizing the attribute can reduce the person to a label and dehumanize them."

====[https://www.sciencedirect.com/journal/current-developments-in-nutrition/publish/guide-for-authors ''Current Developments in Nutrition'']====
*Strongly recommends the use of “people-first language.”

====[https://www.elsevier.com/journals/drug-and-alcohol-dependence/0376-8716/guide-for-authors ''Drug and Alcohol Dependence'']====
*Drug and Alcohol Dependence is committed to eliminating stigmatizing language by adopting "person forward" language when publishing reports of addiction science findings.

====[https://eco2024.org/?p=person-first-language-guide European Association for the Study of Obesity]====
*The European Association for the Study of Obesity requires use of person-first language and non-stigmatizing images in all written and verbal communications.

====[https://www.japha.org/content/authorinfo ''Journal of American Pharmacists Association'' (JAPhA)]====
*To the greatest extent possible, inclusive language should be used throughout the text. Authors are encouraged to use person-first language (e.g., "a person experiencing homelessness" rather than "a homeless person" or "patients with diabetes" rather than "diabetics").

====[http://cfs.cbcs.usf.edu/publications/JBHSRAuthorguidelines.pdf ''Journal of Behavioral Health Services & Research'' (JBHS&R)]====
*Authors are expected to use "person/people first" language (e.g., "individuals with chronic mental disorders" rather than "the chronic mentally ill").

====[https://jneuroengrehab.biomedcentral.com/submission-guidelines/preparing-your-manuscript/research-articles ''Journal of NeuroEngineering and Rehabilitation'']====
*Journal of NeuroEngineering and Rehabilitation recommends the use of person-first language to speak appropriately about individuals with a disability. For example, when referring to a person with a stroke, refer to the person first using a phrase such as 'a person with a stroke' or 'a person who has a stroke'. Avoid terms such as 'victim', 'the handicapped', 'the disabled', or 'brain damaged'.

====[https://heller.brandeis.edu/lurie/pdfs/inclusive-language.pdf Lurie Institute for Disability Policy]====
*People-first language, like “people with addictions,” “people in recovery,” and “people with substance use disorder” is preferable. Avoid terms like addict, substance abuse, junkie, and drug abuse

====[https://www.nami.org/getattachment/About-NAMI/Policy-Platform/Public-Policy-Platform-up-to-12-09-16.pdf NAMI - Public Policy Platform of The National Alliance on Mental Illness]====
*Our language always respects the integrity and the individuality of the people affected by these illnesses. All NAMI documents and NAMI co-authored documents use language that puts people first. For example, "individuals living with serious mental illness" instead of "mentally ill people" or "the mentally ill"; “people living with schizophrenia” instead of “schizophrenics,” and "people who are not criminally responsible" instead of "the criminallyinsane."

====[https://js.sagamorepub.com/index.php/palaestra/about/submissions ''PALAESTRA'']====
*"Reference is to individuals with disabilities, not handicaps, handicapping conditions, or impairments. Authors should apply this person-first policy in their manuscripts."

====[https://publications.aap.org/pediatrics/pages/author-instructions?autologincheck=redirected ''Pediatrics'']====
*Person-first language, which emphasizes the individual or group rather than the condition, disease, or situation, should generally be used, eg, “child(ren) with diabetes” and “child(ren) with obesity” rather than “diabetic child(ren)” and “obese child(ren).” Exceptions to first-person language include certain identity-first language for individuals and groups who prefer it, eg, “Deaf child(ren)” or “autistic child(ren).”

====[https://journals.sagepub.com/pb-assets/cmscontent/poi/Microsoft%20Word%20-%20Recommended%20Terminology_200713.pdf ''Prosthetics and Orthotics International'']====
*Prosthetics and Orthotics International requires that authors use inclusive language, conveying respect to all people and acknowledging diversity.
*When preparing submissions, authors are encouraged to use person-first language emphasising the person and not their disability. For example, authors should use terms such as “a person with an amputation” or “a person who has diabetes”, instead of “amputee” or “diabetic."

====[https://us.sagepub.com/en-us/nam/inclusive-language-guide ''Sage'']====
*Sage is committed to promoting equity throughout our publishing program, and we believe that using language is a simple and powerful way to ensure the communities we serve feel welcomed, respected, safe, and able to fully engage with the publishing process and our published content.
*Person-first language emphasizes the person. Examples:
**“person living with a mental health condition” instead of “mentally ill.”
**“person with a substance use disorder” instead of “addict.”

====[https://academic.oup.com/sleep/pages/General_Instructions ''Sleep'' (official publication of the Sleep Research Society -SRS)]====
*Guidance for improving the language researchers use to talk to and about people with studied health conditions has been issued in several fields. The Editors of SLEEP® endorse the use of people-centered language in research communications. Our recommendations for people-centered language for sleep/circadian research publications can be [https://academic.oup.com/sleep/article/40/4/zsx039/3062257 found on this page].

====[https://journals.sagepub.com/author-instructions/SAJ ''Substance Abuse''] (2024 changing to ''Substance Use and Addiction Journal'')====
*"Non-Pejorative Language - SAj supports the mission AMERSA which is “to improve health and well-being through interdisciplinary leadership in substance use education, research, clinical care, and policy.” The SAj Editorial Team believes that improving health and well-being requires interdisciplinary leadership regarding the language that we use in our scholarship. We ask authors, reviewers, and readers to carefully and intentionally consider the language used to describe alcohol and other drug use and disorders, the individuals affected by these conditions, and their related behaviours, comorbidities, treatment, and recovery in our publication. Specifically, we make an appeal for the use of language that:
**Respects the worth and dignity of all persons (“people-first language”)
**Focuses on the medical nature of substance use disorders and treatment
**Promotes the recovery process
**Avoids perpetuating negative stereotype biases using slang and idioms

====[https://www.sciencedirect.com/journal/the-american-journal-of-clinical-nutrition/publish/guide-for-authors ''The American Journal of Clinical Nutrition'']====
*Strongly recommends the use of “people-first language”

====[https://academic.oup.com/jid/pages/Instructions_For_Authors ''The Journal of Infectious Diseases'' (JID)]====
*Authors should use inclusive and person-first language in manuscripts. Describe people as having a condition or disease, experiencing a circumstance or doing something specific rather than the condition, disease, circumstance or activity being part of their identity. For example, use “people with obesity,” “person with HIV,” “person who injects drugs,” “people experiencing homelessness,” etc.

====[https://www.sciencedirect.com/journal/the-journal-of-nutrition/publish/guide-for-authors ''The Journal of Nutrition'']====
*Strongly recommends the use of “people-first language”

=='''Person/People First Language - Recommendations, Guidelines, Commitments'''==

==='''PFL - Smoking, Tobacco, Nicotine'''===

====American Psychiatric Nurses Association: [https://www.apna.org/wp-content/uploads/2021/03/Tobacco_Dependence_Treatment_Position_Statement_07_20.pdf POSITION STATEMENT: Psychiatric-Mental Health Nursing’s Role in Tobacco Treatment]====
*"Smoking and tobacco use are widely recognized as an addiction, not merely a personal choice, and health care clinicians increasingly address this chronic, relapsing disease using recovery-oriented language. Terms such as “cessation” are being replaced with “treatment” and “smoker” replaced with person-first language such as “person who smokes.”

====Anesthesia Experts - [https://anesthesiaexperts.com/uncategorized/person-first-language-anesthesiology-care/ Person-First Language in Anesthesiology Care]====
*So, is person-first language objectively superior to nonperson-first language? An increasing body of research suggests that it is. Many of the diseases and conditions frequently used to stand in for a person with the condition are those in which there is an unstated or even explicit implication that lifestyle choices are responsible for the condition (alcoholic, addict, diabetic, cirrhotic) or otherwise telegraph shame directed at the patient with the diagnosis (obese, epileptic, smoker). Using person-first language promotes respect and dignity for patients. Describing someone as “a patient with diabetes” rather than “a diabetic” acknowledges that the person is more than just their illness and recognizes their individuality. Using person-first language also helps to avoid stigmatization and discrimination, which can have a negative impact on a patient’s mental and physical well-being (Diabetes Spectr 2018;31:58-64). This may be especially true for mental health conditions, substance use disorders, painful syndromes, eating or body image-related conditions, and in obstetric care (Int J Drug Policy 2010;21:202-7).

====CDC - Centers for Disease Control and Prevention: [https://www.cdc.gov/health-communication/php/toolkit/preferred-terms.html Preferred Terms for Select Population Groups & Communities]====
*Instead of this… "Smokers," Try this... "People who smoke"

====Change Lab Solutions - [https://www.changelabsolutions.org/sites/default/files/2022-03/Justice-in-the-Air-Framing-Tobacco-Related-Health-Disparities_FINAL_20220307A.pdf Justice In The Air: Framing Tobacco-Related Health Disparities A FrameWorks Strategic Brief ]====
*Use person-first language. Avoid labeling people as “smokers” or “tobacco users.” Instead, start with people, then add any necessary qualifiers: people who smoke, people with a dependence on nicotine.

====[https://www.denverhealth.org/-/media/files/departments-services/behavioral-health/cam/cam2310-43-words-matter-language-guide-web-d-final Denver Health Center for Addiction Medicine (CAM)]====
*Use tobacco use disorder instead of smoker.
*Person-first language can reduce stigma – a patient “has” rather than “is” a condition
*Avoids negative bias, punitive attitudes, and blame

====NCSCT - [https://twitter.com/NCSCT/status/1727984982897910117 The National Centre for Smoking Cessation and Training]====
*The NCSCT has committed to using ‘people first’ language wherever possible, so instead of ‘smoker’ we will talk about ‘people who smoke’ or just ‘people’

====2024: [https://www.nice.org.uk/corporate/ecd1/chapter/talking-about-people NICE style guide - Talking about people]====
*[https://www.nice.org.uk/media/default/About/what-we-do/wg1-style-guide.docx NICE style guide (downloadable document)]
*'''Smoker: Do not use. In line with our house style, we do not label people. Use 'people who smoke'.''' [emphasis added]
*Don't label people with their condition: we would never say 'epileptics', 'schizophrenics', 'smokers', 'drug-takers'. Use the following as a guide: 'people with epilepsy', 'people with schizophrenia', 'people who smoke', 'people who take drugs'.

====NYC - [https://www.nyc.gov/assets/doh/downloads/pdf/survey/tobacco-inequities-2022.pdf Addressing New York City’s Smoking Inequities]====
*Use person-first language (“person who smokes” not “smoker”).

====Rosh Review - [https://www.roshreview.com/blog/inclusive-language-for-medical-education-and-qbanks-an-evolving-guide/ Inclusive Language for Medical & Health Education: An Evolving Guide]====
*Instead of: smoker (e.g., patient is a smoker)
**Use: smokes (e.g., patient smokes cigarettes)

====STR - [https://thoracicrad.org/wp-content/uploads/2022/01/4083-STR-Newsletter-r5.pdf Society of Thoracic Radiology]====
*STR’S COMMITMENT TO NON-STIGMATIZING LANGUAGE IN LUNG CANCER CARE
*"Whether we as chest imagers realize it or not, our very language can have a negative impact on the care for the patients we serve. As published studies continue to demonstrate, smoking-related language bias often stigmatizes our patients with a smoking history and results in suboptimal care and less than desirable clinical outcomes... Instead of a report stigmatizing the patient as a “smoker,” consider describing the patient as a “person who smokes.” Rather than a “nicotine addict,” an expression such as a “person with a nicotine dependence” attenuates the common stigmatization of these patients. One will notice these alternative descriptors utilize a person-first approach rather than a habit-based one. This approach can and should be adopted in publications, society and conference presentations as well as in daily training with residents and fellows. Ultimately, this language shift more precisely aligns itself with a core underpinning of our approach to care – respect for our patients.

====Truth Initiative's Ex Program - [https://www.theexprogram.com/resources/blog/how-to-reduce-mental-health-stigma-smoking-stigma-in-the-workplace/ How to Reduce Mental Health Stigma, Smoking Stigma in the Workplace]====
*It can be tempting to dismiss these kinds of negative labels as simply semantics, but research has shown that language matters. Using person-first language like “people who smoke” instead of “smokers” acknowledges the tenacity of this disease, conveys dignity and greater respect, and can reduce smoking-related stigma.

====University of Melbourne - [https://www.canceraustralia.gov.au/sites/default/files/the_program_tools_guidance_information_and_communication_workforce_considerations_and_aboriginal_and_torres_strait_islander_considerations_for_a_lcsp_-_the_university_of_melbourne_-_2022_-_.pdf Melbourne School of Population and Global Health]====
*All communications materials aimed toward potential and enrolled LCS participants must be created sensitively and incorporate the plain English guidelines to be accessible to those with low levels of health literacy. This includes clear, short sentences that use active verbs. It is also important to avoid stigmatizing language, as this can affect the care provided to patients, impact the attitude of other health care providers towards the patient, and can adversely impact health outcomes. Therefore, language used within such materials – from promotion materials to results letters – must aim to reduce the burden of stigma already experienced by these high-risk populations.
*As part of a communications strategy, the International Association of Lung Cancer (IALSC) Language Guide should be adopted across all communications tools and resources and be included as part of HCP education and training.
**IASLC’s four simple principles:
***Use person-first language. For example, instead of “lung cancer patient” use “patient/person with lung cancer.”
***Eliminate blaming language. For example, replace “patient failed treatment” with “treatment failed patient.”
***End stigma. For example, instead of “smoker” use “person who smokes.”
***Equity. Follow best practices regarding race, ethnicity, gender, socioeconomic, and geographic descriptions to promote cultural humility and sensitivity.

==='''PFL - Not Tobacco'''===

====ADA National Network - [https://adata.org/factsheet/ADANN-writing Guidelines for Writing About People With Disabilities]====
*In general, refer to the person first and the disability second. People with disabilities are, first and foremost, people. Labeling a person equates the person with a condition and can be disrespectful and dehumanizing. A person isn’t a disability, condition or diagnosis; a person has a disability, condition or diagnosis. This is called Person-First Language.
*However, always ask to find out an individual’s language preferences. People with disabilities have different preferences when referring to their disability. Some people see their disability as an essential part of who they are and prefer to be identified with their disability first – this is called Identity-First Language. Others prefer Person-First Language. Examples of Identity-First Language include identifying someone as a deaf person instead of a person who is deaf, or an autistic person instead of a person with autism.

====INPUD: [https://inpud.net/words-matter-language-statement-reference-guide/ Words Matter! Language Statement & Reference Guide]====
*Recommends person-first language.
*"Compiled by INPUD and the Asian Network of People who Use Drugs (ANPUD), this guide aims to explain our current position on the use of language and to provide clear advice on what is acceptable to us as communities of people who use drugs. We want to encourage all people to be thoughtful about the language and words they use, and have therefore provided a reference guide that identifies stigmatising language and gives non-judgemental, strengths-based, and respectful alternatives."

====Massachusetts Down Syndrome Congress - [https://mdsc.org/programs/people-first-language/ People First Language]====
*As part of the disabilities rights movement, MDSC promotes the use “People First language” because people with disabilities are NOT their diagnoses or disabilities. They are PEOPLE first. MDSC is not only committed to using People First language in all materials, statements, and interactions. We also work to educate and encourage the community at large to do the same.

====Minnesota Organization for Habilitation and Rehabilitation - [https://mohrmn.org/blog/165-people-first-language MOHR supports People First Language]====
*Although a disability has an impact, it is only a small part of a person’s identity. No one is their disability. We encourage you to see people with disabilities as people, first. Using the “People First” language we describe is one way to let people know you see them, not just their disability. When you see people first, you and they will notice the difference.

====[https://www.narcolepsy.org.uk/resources/%E2%80%98narcoleptic%E2%80%99-or-%E2%80%98-person-narcolepsy%E2%80%99 Narcolepsy UK]====
*The Narcolepsy Charter champions the right for people with narcolepsy “to live in a society that understands and recognises the impact of narcolepsy” and encourages “the ability to talk about narcolepsy without fear or judgement”. Given that referring to “narcoleptics” rather than “people with narcolepsy” is very likely to perpetuate unhelpful stereotypes and negative attitudes, Narcolepsy UK encourages people with and without narcolepsy to put people first and avoid the term “narcoleptics” or “narcolepsy patients” in favour of “people with narcolepsy”.

====United Nations Office at Geneva - [https://www.ungeneva.org/sites/default/files/2021-01/Disability-Inclusive-Language-Guidelines.pdf DISABILITY-INCLUSIVE LANGUAGE GUIDELINES]====
*This document contains recommendations that United Nations staff, experts and collaborators can use in their oral and written communications on disability or other subjects, including speeches and presentations, press releases, social media posts, internal communications and other formal and informal documents.
*People-first language is the most widely accepted language for referring to persons with disabilities. It is also the language used in the Convention on the Rights of Persons with Disabilities. People-first language emphasizes the person, not the disability, by placing a reference to the person or group before the reference to the disability. For example, we can use expressions such as “children with albinism”, “students with dyslexia”, “women with intellectual disabilities” and, of course, “persons with disabilities”.
*However, the people-first rule does not necessarily apply to all types of disabilities. There are some exceptions. (Deaf, Blind, Autistic)

=='''Publication Policies - Language (General)'''==

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/add.16302 How ''Addiction'' handles disagreements over potentially harmful terminology]===
*[https://twitter.com/KeithNHumphreys/status/1684288642834137088 Twitter(X) Thread by Lead Author]
*Editors, reviewers, authors and readers of ''Addiction'' agree that journal articles should not contain terminology that harms vulnerable groups, but disagree about which terms those are and what should replace them. ''Addiction'' therefore promotes principled, civil discussion when such disagreements occur.
*PRINCIPLE 1: EVERYONE IS ALLOWED TO REFER TO THEMSELVES AS THEY WISH
*PRINCIPLE 2: WHETHER A POPULATION WANTS TO BE CALLED A PARTICULAR TERM IS AN EMPIRICAL QUESTION
*PRINCIPLE 3: WHETHER ANY PARTICULAR TERM IS HARMFUL IS AN EMPIRICAL QUESTION
*PRINCIPLE 4: HISTORICAL ACCURACY IS A SCHOLARLY OBLIGATION
*Article: [https://www.theatlantic.com/ideas/archive/2023/08/addiction-drug-policy-language-harm-evidence/674907/ The Burden of Proof Is on the Language Police]

=='''Speaker/Presenter Policies'''==

===[https://academicmedicaleducation.com/person-first-language Academic Medical Education]===
*We are proud to support and officially endorse the [https://peoplefirstcharter.org/ People First Charter]! Language matters - the use of positive and inclusive language is a vital tool in tackling stigma and discrimination. Person-first language simply puts people before their condition, recognizing that people are people, and are not defined by their condition. In HIV care, we should avoid terms like 'HIV-infected people' and use 'people living with HIV'. As a participant, faculty member, or abstract presenter at one of our programs, we encourage you to consult these guidelines as you prepare program-related materials.

===[https://acpacares.org/annual-meeting/abstract-submission/abstract-guidelines-2024-annual-meeting/ American Cleft Palate Craniofacial Association (ACPA) Annual Meeting]===
*When preparing an abstract, remember that ACPA requires that all abstracts use person first language, e.g., instead of “cleft patient” use “patient with a cleft.”

===[https://web.archive.org/web/20231126125124/https://amersa.confex.com/amersa/2023/cfp.cgi AMERSA National Conference]===
*‘PEOPLE FIRST’ language is required for the abstracts (e.g. person with alcohol use disorder instead of ‘alcoholic’). Examples of appropriate terminology are provided in the editorial in Substance Abuse, cited below, and accessible at https://pubmed.ncbi.nlm.nih.gov/24911031/
*Broyles, L.M., Binswanger, I.A., Jenkins, J.A., Finnell, D.S., Faseru, B., Cavaiola, A., Pugatch, M. & Gordon, A.J. (2014). Confronting inadvertent stigma and pejorative language in addiction scholarship: A recognition and response. Substance Abuse, 35(3), 217221.

===[https://www.aptapa.org/assets/committees/Practice-Research/2023/Abstract%20Submission%20Guidelines.2023.pdf APTA Pennsylvania Annual Conference ]===
*American Physical Therapy Association - Pennsylvania
*5. Professional Presentation/Quality
**a. Adherence to formatting requirements evident.
**b. Abstract clearly and concisely written.
**c. Use of correct spelling and proper grammar.
**d. Use of people first and inclusive language.

===[https://web.archive.org/web/20231126185644/https://files.sciconf.cn/upload/file/20230804/20230804172139_14226.pdf Asian Congress on Nutrition]===
*Oral Abstract Presentation Guidelines... Use people-first language: We encourage presenters to use people-first language when referring to individuals. This means describing individuals as people with a medical condition rather than focusing on their diseases or disabilities. This promotes inclusivity and respect.

===[https://www.croiconference.org/abstract-guidelines-and-submission/#1695946522329-9dcf2cdc-4ef0 Conference on Retroviruses and Opportunistic Infections (CROI)]===
*It is important to use “people first” language such as “people with HIV” rather than “HIV-infected people.” Similarly, do not characterize people by their conditions. “People with diabetes” is preferred over “diabetics”; “patients with cirrhosis” rather than “cirrhotics;” and “people who inject drugs” rather than “drug abusers.” Out of respect for their contributions to our scientific advances, avoid calling study volunteers “subjects.” The preferred terms are study “participants” or “volunteers.”

===[https://eacs-conference2023.com/abstracts/abstract-guidelines/ European AIDS Conference (EACS)]===
*We strongly encourage anyone who submits an abstract or clinical case to use people first language.

===[https://eco2024.org/?p=abstract-submission European Congress on Obesity]===
*Please ensure that you refer to the EASO Person First Language Guide when preparing your abstract AND developing your presentation. Please note that '''abstracts that do not use Person First Language will be rejected'''.

===[http://interestworkshop.org/abstracts/ INTEREST 2024]===
*Abstract submitters are strongly encouraged to use person-first language in their abstracts.

===[https://www.ilcn.org/the-iaslc-language-guide-a-lexicon-of-healing-for-lung-cancer-and-beyond/ International Association for the Study of Lung Cancer - The IASLC Language Guide: A Lexicon of Healing for Lung Cancer and Beyond 2021]===
*The Guide is not long, dense, or difficult to understand. It encourages everyone to “take conscious steps to be thoughtful in the language we use,” and boils down to four simple, subtle principles:
**Use Person-First Language: For example, instead of “lung cancer patient,” use “patient/person with lung cancer.”
**Eliminate Blaming Language: For example, replace “patient failed treatment” with “treatment failed patient.”
**End Stigma: For example, instead of “smoker,” use “person who smokes.”
**Equity: Follow best practices regarding race, ethnicity, gender, socioeconomic, and geographic descriptions to promote cultural humility and sensitivity.
*“We came together from different places, with different methods and different training, but we all agree that words matter, and that it is possible to change the language we use to talk to and about persons with lung cancer, as well as about people who use tobacco,” Dr. Ostroff said. “And we can do that in a way that that conveys respect, inclusivity, and equity.”
**'''Follow-up on new policy''': 2024: Preprint: [https://www.jtocrr.org/article/S2666-3643(24)00081-X/pdf Brief Report: Precision Language and Deletion of the “S” Word 2022]
**"In 2021 the International Association for the Study of Lung Cancer (IASLC) published the IASLC Language Guide as guidance on preferred language and phrasing in oral and written communications, including presentations at conferences. This study analyzed presentations from the 2022 IASLC World Conference on Lung Cancer (WCLC) one year after implementation of the Language Guide to identify adoption rates of non-stigmatizing language and to determine correlations with presenter characteristics."
**We searched each presentation, including images, for discussion of tobacco use, and the use of the term “smoker,” which is an indicator of stigmatizing language.
**Of 177 presentations that discussed smoking status 77 presenters used non-stigmatizing language while 100 presenters used the stigmatizing term "smoker". Male MDs and female PhDs and non-medicine subspecialties and advocates were more likely to use non-stigmatizing language.
**Encouragingly, only after one year post release of the Language Guide, greater than one-third of the presenters at the WCLC used non-stigmatizing language. This finding represents a step towards improving respectful and inclusive language surrounding smoking within the thoracic oncology community.

===[https://media.nutrition.org/wp-content/uploads/2023/04/N23-Abstract-Presentation-Guidelines.pdf NUTRITION 2023]===
*As you prepare for your presentation at NUTRITION 2023, ASN strongly recommends that presenters use people-first language. This includes describing individuals as people with a medical condition rather than as diseases or disabilities. Terms such as “adults with obesity” and “children with diabetes” are preferred over “obese adults” and “diabetic children”. For more information consult “Use of people-first language with regard to obesity” Am J Clin Nutr 2018;108:201 or “The Effect of Words on Health and Diabetes” Diabetes Spectrum 2017;30:11- 16.

===[https://web.archive.org/web/20231126130140/https://obesityweek.org/wp-content/uploads/2023/04/TOS-OW23-Late-Breaking-Call-for-Abstracts-Instructions.pdf Obesity Society's 41st Annual Scientific Meeting]===
*PEOPLE FIRST LANGUAGE: The Obesity Society requires use of person-first language and nonstigmatizing images in all written and verbal communications. For more information please visit: https://obesityweek.org/abstracts/speaker-resources/person-first/.

===[https://www.pas-meeting.org/wp-content/uploads/2024-Tips-for-Quality-Abstracts.pdf Pediatric Academic Societies Meeting]===
*Please use People-First Language in your abstracts and presentations to respectfully refer to individuals with chronic conditions and disabilities. This language refers to the person first, not the condition or disability. It serves to eliminate bias, labels, stigma, and discrimination. Some examples: “children with obesity” instead of “obese children,” or a “child with a developmental delay” instead of a “developmentally delayed child.”

===[https://aso.org.uk/ukco/abstracts UK Congress on Obesity (UKCO)]===
*The use of People-First Language is mandatory for the abstract to be accepted. Abstracts not using People-First Language will be rejected.

=='''Guidelines - Journalists and Editors'''==

===[https://www.seebeyondscotland.com/language-and-media See Beyond – See the Lives – Scotland, Language and Media]===
*While this guide does not mention smoking or nicotine, it provides helpful suggestions on ways to avoid stigma when writing about the use of substances, that are applicable to smoking and nicotine.

=='''Videos'''==

===2024: Breathe Easy Maine Webinar [https://www.youtube.com/watch?v=vdH__irCcY8 Addressing the Harmful Effects of Tobacco-Related Stigma]===
*Presenter: Derek Bowen, MaineHealth Center for Tobacco Independence
*Stigma is the public’s effect of marking disgrace of a certain quality within a targeted community. People who use tobacco are faced with stigma and the challenges it brings day by day, and it leaves a great impact on the individual’s quality of life, mental health, and likeliness to stop using tobacco further down the road. Within the webinar, we will discuss different types of stigmas, the effects of stigma, and ways to reduce and prevent stigma when it comes to individuals who use tobacco.

===2021: E-Cigarette Summit: [https://vimeo.com/572107642 Stigma and tobacco harm reduction: what we can learn from other health behaviors]===
*[https://www.e-cigarette-summit.us.com/speaker/prof-scott-leischow/ Prof Scott Leischow]
*Stigmatizing smoking has been at the heart of tobacco control efforts for decades, which may drive more people to quit but at the same time potentially create new difficulties for smokers, including self-isolation, creation of social groups that might become ‘hardened’ to changing smoking behaviors, and perceptions by the user and society that complete abstinence is the only option. The stigma associated with a wide variety of behaviors has impeded progress toward improving population health in some cases, such as the reticence in making products and services available that could reduce the risk of communicable disease (eg needle exchanges), as well as harm reduction products that could benefit users and society when an individual addicted to a substance is not able to or chooses not to become completely abstinent (eg NRT, ENDS, smokeless tobacco). This presentation will explore some of the conflicting aspects of stigma in tobacco control, explore similarities and differences regarding the stigma of using of different addicting substances, and consider some research, practice and policy directions.

===2017: Video: [https://vimeo.com/246425657 Sarah Jakes]===
*Ecig Summit UK

===[https://vimeo.com/314638943 Let's Break the Stigma]===
*How are you doing? How are you really doing?

=='''Studies, Papers, Reports - Smoker'''==

===2022: [https://www.mdpi.com/1660-4601/19/9/5628/htm A Person-Centered Approach to Moralization—The Case of Vaping]===
*The public should be educated about the difficulties in exercising self-control in addictions, such as nicotine addiction, and other lifestyle-related afflictions, such as obesity, so that moralization and its social consequences are less likely to occur. Such cognitively-oriented initiatives should be accompanied by emotionally oriented ones, aiming to sensitize the public to the moralized groups’ suffering.

===2021: [https://cdn.ymaws.com/www.srnt.org/resource/resmgr/racial_equity/sheffer_-_tobacco_related_di.pdf Tobacco-Related Disparities Viewed Through the Lens of Intersectionality]===
*Changes in our language can convey a less stigmatizing description of individuals (eg, person who smokes instead of “smoker”).

===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238180/ Internalized stigma among cancer patients enrolled in a smoking cessation trial: The role of cancer type and associations with psychological distress]===
*To balance these factors, complementary campaigns can address the role of media and the tobacco industry in promoting smoking, making it clear that smoking is not solely driven by personal decision making, emphasize that smoking is a physical and behavioral addiction and not a personal moral failing, '''use person-first language (people who smoke vs. smokers)''', emphasize the positive benefits of quitting, and acknowledge that quitting is difficult and may take multiple tries but there are treatment strategies that can help. [emphasis added]

===2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733058/ Changing the Language of How We Measure and Report Smoking Status: Implications for Reducing Stigma, Restoring Dignity, and Improving the Precision of Scientific Communication]===
*However, the descriptors we commonly use to classify people who smoke may inadvertently perpetuate harmful, stigmatizing beliefs and negative stereotypes. In recognizing the power of words to either perpetuate or reduce stigma, Dr. Nora Volkow—Director of the National Institute on Drug Abuse—recently highlighted the role of stigma in addiction, and the movement encouraging the use of person-first language and eliminating the use of slang and idioms when describing addiction and the people whom it affects.
*In this commentary, '''we make an appeal for researchers and clinicians to use person-first language (eg, “people who smoke”) rather than commonly used labels (eg, “smokers”)''' in written (eg, in scholarly reports) and verbal communication (eg, clinical case presentations) to promote greater respect and convey dignity for people who smoke. We assert that the use of precise and bias-free language to describe people who smoke has the potential to reduce smoking-related stigma and may enhance the precision of scientific communication. [emphasis added]

===2020: [https://ajph.aphapublications.org/doi/ref/10.2105/AJPH.2020.305628 Stigma, Opioids, and Public Health Messaging: The Need to Disentangle Behavior From Identity]===
*"Indeed, an oft-spoken proverb among those who work in tobacco control is''' “There is no such thing as a ‘smoker,’ there are only people who smoke." '''This framing intentionally creates space to decouple behavior from identity, so that unhealthy behavior (i.e., smoking) can be actively denormalized without perpetuating stigma against those who engage in it. It underscores that individuals who smoke maintain their core humanity and value as human beings, despite engaging in a socially unacceptable behavior. Once they change this target behavior, they are no longer targeted for disapproval." [emphasis added]

===2020: [https://facesandvoicesofrecovery.org/wp-content/uploads/2020/06/Zgierska-2020-JAM-Language_Matters52.pdf Language Matters: It Is Time We Change How We Talk About Addiction and its Treatment]===
*Stigmatizing language can worsen addiction-related stigma and outcomes. Although non-professional terminology may be used by individuals with addiction, the role of clinicians, educators, researchers, policymakers, and community and cultural leaders is to actively work toward destigmatization of addiction and its treatment, in part through the use of non-stigmatizing language.
**Stigmatizing Language: Smoker
**Proposed Terminology: Person with cannabis and/or tobacco or nicotine use disorder, or addiction involving cannabis / tobacco / nicotine use.

===2019: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.14696 The ironic effects of stigmatizing smoking: combining stereotype threat theory with behavioral pharmacology]===
*Related Article: [https://anderson-review.ucla.edu/smoking-stereotype/ Shaming Smokers Actually Increases Their Urge to Light Up]
**In a study, smokers who were confronted with negative stereotypes commonly associated with smoking were more compelled to light up sooner than smokers who weren’t thusly goaded.

===2016: [https://academic.oup.com/ntr/article/18/8/1684/2492710 Exploring Issues of Comorbid Conditions in People Who Smoke]===
*For the purposes of this manuscript, we have attempted to reduce the stigma associated with smoking and support a more holistic approach by referring to''' “individuals who smoke” or “patients who smoke” rather than referring to people as “smokers.” '''In other words, tobacco dependence is just one component of an individual’s health behaviors and diagnoses. [emphasis added]

===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042508/ Confronting Inadvertent Stigma and Pejorative Language in Addiction Scholarship: A Recognition and Response]===
*"For these reasons, the Editorial Team of ''Substance Abuse'' seeks to formally operationalize respect for personhood in our mission, our public relations, and our instructions to authors. To our knowledge, few journals have explicitly taken this step,7–12 and we are the first scientific addiction journal to do so. Our overarching call is threefold. First, we are asking authors to carefully and intentionally consider the language they use to describe alcohol and other drug use and disorders, the individuals affected by these conditions, and their related behaviors, comorbidities, treatment, and recovery..."

===2013: [https://irp.cdn-website.com/a4ee3539/files/uploaded/PIC_Tasmania_Report_2013.pdf Partners in Change Report on participation in a health behaviour change course to address smoking in pregnancy in support of a fair and equal Tasmania]===
*Appendix C. Comments on antcipated changes to practce:''' 'people who smoke' not 'smoker' '''[emphasis added]

===2013: [https://journals.sagepub.com/doi/abs/10.1177/009145091304000107 After the Smoke Has Cleared: Reflections from a Former Smoker and Tobacco Researcher]===
*[https://sci-hub.se/10.1177/009145091304000107 Sci-Hub (full paper)]
*I use the terms “tobacco user” and “people who smoke” to counter the pejorative implications of the term “smoker(s)”
*I found that most of the tobacco and health advocates I encountered held dismissive and demeaning views about people who smoke...

===2012: [https://academic.oup.com/ntr/article-abstract/15/2/552/1058604 Crossing the Smoking Divide for Young Adults: Expressions of Stigma and Identity Among Smokers and Nonsmokers]===
*The themes identified illustrated how nonsmokers’ perception of smoking as illogical and self-destructive supported harsh reactions, including stigmatizing behaviors that antagonized smokers.
*A supportive/empathic tobacco-control denormalization approach could enhance young adult smokers’ willingness to make the transition from smoker to smoke free and elicit stronger support for their efforts from nonsmokers.

=='''Editorials, Articles, Websites, Blogs - Smoker (Some from Journals)'''==

===2025: Nicotine and Tobacco Research: Editorial: [https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntaf003/7944756 Person-First Language in Nicotine and Tobacco Research]===
*Click on "PDF" to read the editorial
*"Embracing person-first language is a crucial step toward scientific precision in language use, and will help to achieve an equitable and respectful approach to research on nicotine and tobacco use. By prioritising the individual over their behaviour, we as a research community can foster a culture of linguistic accuracy and precision, which also demonstrates empathy and understanding towards those who use nicotine or tobacco containing products."

===2024: International Journal of Drug Policy: Editorial: [https://www.sciencedirect.com/science/article/pii/S0955395924002007 Guiding principles for breaking down drug-related stigma in academic writing]===
*“…although stigma relating to alcohol, tobacco and prescription medicines is increasingly well documented…This stigmatisation is produced through words like “criminal”, “abuser”, “junkie”, “alcoholic”, "smoker" and “addict”. These kinds of words have functioned in tandem with corresponding normative reactions such as fear and disgust, to justify and legitimise stereotyping, discrimination, punishment, social control and exclusion, and create significant obstacles to treatment, harm reduction, support, health and wellbeing.”

===2023: The Lancet Oncology: Editorial: [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00465-5/fulltext Patient first; person first]===
*"Dehumanising and stigma-laden terminology is rife in medicine, with oncology being no exception, and blame-ridden language is too often used when referring to people at risk for or who have cancer. Although not coming from a place of malice, or indeed reflective of an intentional effort to offend, these phrases are typically used as shorthand in an effort to aid communication, but the lack of empathy and awareness that accompanies the use of such language could also be linked with apathetic attitudes."
*"Presenters at the conference promoted the benefits of implementing the IASLC Language Guide, which emphasises the importance of using person-first language (eg, using patient or participant rather than subject, and person with active tobacco use rather than smoker), eliminating blame language (using unable to comply rather than non-compliant), and ending stigma (such as noting a person who does not smoke rather than a non-smoker)."

===2023: Filter: Article: [https://filtermag.org/smoker-person-first-language/ Is It Time to Abandon the Term “Smoker”?]===
*It’s exactly that stigma that society has attached to the word—leaving little room for nuance or reinvention in the fixed, judgemental glare of a label—that’s prompting growing numbers to move away from its use.

===2023: FINN Partners: Blog: [https://www.finnpartners.com/news-insights/watch-your-language-words-matter-in-scientific-and-health-communications/ Watch Your Language: Words Matter in Scientific and Health Communications]===
*"While some language conventions have stagnated, others have started to move in more positive directions. For example, terms such as “diabetic” or “smoker” are being replaced with “a person living with diabetes” and “a person who uses cigarettes.” While the former terms were always clearly understood, they had the effect of defining the individuals as their disease or risk factor. The latter terms acknowledge the person first."

===2022: Nicotine & Tobacco Research: Editorial: [https://academic.oup.com/ntr/article/24/12/1847/6710205 Time to Stop Using the Word “Smoker”: Reflecting on the Role of Language in Advancing the Field of Nicotine and Tobacco Research]===
*From legislatures to schools to workplaces, as well as in scientific discourse and clinical practice, the past few decades have seen a move away from labels such as “user,” “addict,” or “alcoholic,” for their lack of precision, negative connotation, and the way they equate the person with behavior or condition. Despite this, “smoker” remains in use in tobacco research, as well as in clinical settings and public health policy.

===2022: John Oyston: Blog: [https://oyston.com/blog/pws/ PWS – People Who Smoke]===
*The word “smoker” is a disparaging term, like “addict” or “alcoholic”
*The use of a label such as “smoker”, “addict” or “illegal” divides people up into “us” and “them”. It is a slippery slope toward calling certain groups or tribes “vermin” or “cockroaches”

===2022: EX Program by Truth Initiative: Blog: [https://www.theexprogram.com/resources/blog/how-to-reduce-mental-health-stigma-smoking-stigma-in-the-workplace/ How to Reduce Mental Health Stigma, Smoking Stigma in the Workplace]===
*It can be tempting to dismiss these kinds of negative labels as simply semantics, but research has shown that language matters. '''Using person-first language like “people who smoke” '''instead of “smokers” acknowledges the tenacity of this disease, conveys dignity and greater respect, and can reduce smoking-related stigma.
*People who smoke are often perceived as having negative personality and social traits.
*These aren’t silent biases either: these negative perceptions influence attitudes about people who smoke, which in turn influence non-smokers’ willingness to interact with people who smoke.
*...there are 21 states that do not offer employment protection to tobacco users, allowing employers to refuse to hire people who smoke. Unsurprisingly, people who smoke have a harder time getting hired. For example, the chances of getting a job within a year is reduced by 24% for unemployed job seekers who smoke compared to non-smokers, even when other factors like criminal history are considered.
*And even with a job, the stigma still carries through, as people who smoke earn 20% less compared to non-smokers.
*Stigma associated with many mental health conditions like depression is now a well-recognized issue. By acknowledging this stigma, it has allowed considerable progress to be made. Unfortunately, the same progress has not been made in reducing the stigma of substance use disorders like nicotine addiction.

===2021: ECOG-ACRIN Cancer Research Group: Blog: [https://blog-ecog-acrin.org/a-new-guide-encourages-the-use-of-language-that-is-respectful-of-patients-free-of-stigma-inclusive-and-equitable/ A New Guide Encourages the Use of Language that is Respectful of Patients, Free of Stigma, Inclusive, and Equitable]===
*'''End stigma: Promote judgment-free, bias-free language. Try 'person who smokes' rather than 'smoker.' ''' [emphasis added]
*'A person with nicotine dependence' instead of 'a nicotine addict.'

===2021: [https://www.apna.org/news/psychiatric-mental-health-nursings-role-in-tobacco-treatment/ American Psychiatric Nurses Association]===
*"Smoking and tobacco use are widely recognized as an addiction, not merely a personal choice, and health care clinicians increasingly address this chronic, relapsing disease using recovery-oriented language. Terms such as “cessation” are being replaced with “treatment” and “smoker” replaced with person-first language such as “person who smokes.”"
*[https://web.archive.org/web/20230326001139/https://www.apna.org/news/psychiatric-mental-health-nursings-role-in-tobacco-treatment/ Link on WayBack Machine]

===2019: Filter: Article: [https://filtermag.org/how-widespread-anti-smoker-stigma-is-harmful-as-well-as-wrong/ Widespread Anti-Smoker Stigma Is Harmful, as Well as Wrong]===
*"Ordinarily, stigmatizing a disease or observing medical practitioners making decisions based on social characteristics would raise the hackles of the public health community. With smoking, however, this hasn’t been the case. In fact, many anti-smoking campaigns actually turn to stigmatization as a behavioral control tactic."

===Comments by people who don't smoke===
*2021: [https://cfrankdavis.files.wordpress.com/2014/12/masterhatefinalc45x30-custom.jpg The Wall of Hate]
**130 comments found online. Some of those comments suggest violence against people who smoke
**[https://wall-of-hate.quora.com/The-Wall-Of-Hate-The-Wall-Of-Hate-For-best-close-up-reading-visit-the-poster-size-and-freely-downloadable-external-imag Wall of hate info]
*2014: [https://newrepublic.com/article/116553/smoking-and-stigma-war-smoking-has-gone-too-far Let's Not Wage War on Smokers]
**In 2006, sociologist Hannah Farrimond and psychologist Helene Joffe asked 40 British adults what they thought about smokers. It wasn’t nice. Non-smokers use terms such as ‘outcast’, ‘persecuted’, ‘lepers’, ‘under-class’ and ‘blacklisted’ to describe smokers’ status in society….Non-smoking participants associate smokers with a strong negative aesthetic. This comprises two aspects, smell (e.g. ‘reek’, ‘pong’, ‘stink’, ‘stale’, ‘old’) and negative appearance (‘stained yellow fingers’, ‘grey, dry, wrinkly skin’, ‘brown teeth’)…several non-smokers see smokers as lacking in cleanliness and engaging in poor self-care.

===2021: [https://www.medicalnewstoday.com/articles/lung-cancer-stigma-holds-back-treatment-research MNT investigates: How lung cancer stigma holds back research and treatment]===
*Drs. Carter-Harris and Williamson both encourage people to use person-first language when talking about smoking. One example of this is describing someone as “a person who formerly smoked” rather than “a former smoker.”
*“By labeling someone as a smoker, you’ve depersonalized them, and you’ve identified them by a behavior that’s stigmatized,” Dr. Carter-Harris said.

===2014: [https://theindefatigablefrog.blogspot.com/2014/09/the-indefatigable-frog-or-why-this-wont.html The Indefatigable Frog, or Why this won't stop us!]===
*"Remember that poor woman who ignited her oxygen tube with a lighter? Seek it out – look at the comments and see what the public thinks of smokers. The vitriol and hatred is something to behold. A poor woman made a horrible mistake whilst still under the effects of a general anaesthetic and what did the public say? She deserved it. Why? Because she was a smoker."

===2014: [https://newrepublic.com/article/116553/smoking-and-stigma-war-smoking-has-gone-too-far Let's Not Wage War on Smokers]===
*In 2004, a team of health scientists at Oxford interviewed 45 people with lung cancer and found that felt even more stigma than other cancer patients: Participants experienced stigma commonly felt by patients with other types of cancer, but, whether they smoked or not, they felt particularly stigmatized because the disease is so strongly associated with smoking… Some patients concealed their illness, which sometimes had adverse financial consequences or made it hard for them to gain support from other people.

=='''Tweets about discontinuing the use of "Smoker," or using person-first language'''==

===[https://twitter.com/MarewaGlover/status/1719683510368424372 Prof Marewa Glover]===
*I encourage authors who submit to Harm Reduction Journal Tobacco Section to use person-centred language. People are not defined by 1 behaviour they do.

===[https://twitter.com/tarahaelle/status/1718367680825053260 Tara Haelle]===
*I write “people who smoke/have smoked.” I haven’t read any research on this particular term, but referring to “smokers” in journalistic articles never sat well w me bc it reduces people’s identity to a single activity that may be one they’ve tried to quit.

===[https://twitter.com/imaracingmom/status/1557396600636547072 Skip Murray]===
*What would it take for me to convince the scientific and public health communities to switch from the stigmatizing word "smokers" and switch to something else? Perhaps "people who smoke (PWS)."

===[https://twitter.com/CrisDelnevo/status/1557455819301482496 Cristine Delnevo, PhD, MPH, FAAHB]===
*You're 100% correct - admittedly, when on autopilot, I've written "smokers" and revised when editing. I'm a fallible human, a work in progress, and trying to do better. What would it take? keep calling us out on it! we need to retrain our brains.

===[https://twitter.com/MaloneRuth/status/1557478522800574471 Ruth Malone PhD]===
*This is right & we’ve had a lot of conversations about this at TC_BMJ but I know some still slip through. Anyway, the point is our concern ought to focus on these horrible products, not on individual behaviors. Thank you for this reminder.

===[https://twitter.com/AmandaPalmerPhD/status/1579874426598068229 Amanda Palmer, PhD]===
*When reviewing articles that use the word "smoker" or something similar, I suggest to the authors to use person-centered language and then write a nice note to the editor encouraging wiggle room with the word limit
**Reply by [https://twitter.com/bentollphd/status/1580225898917552129 Benjamin Toll]: This is a great thread! I also want to alert everyone to Jamie Ostroff's great article on same topic: https://ncbi.nlm.nih.gov/pmc/articles/PMC7733058/ I am thrilled to see @MaloneRuth considering for @TC_BMJ & I hope you are addressing word limits? It is the major hurdle for me with papers and grants
**Reply by [https://twitter.com/larryhawkjr/status/1580157877934645250 Larry Hawk]: Old habits are hard to break, but we are behavior change specialists. I'm committed to change and will roll with the occasional slips/relapses. PWS, not smokers. PWS, not smokers...

===[https://twitter.com/Dana_Bourne/status/1542200997061197828 Dana Elizabeth Bourne, MPH]===
*Hearing "smoker" a lot....at @healthvermont we prefer "person who uses tobacco" or "tobacco user" to remove the stigma, and use people-first language.

===[https://x.com/RamezBathish/status/1829008643527979483 Ramez Bathish]===
*New paper - Centering authors' responsibility to engage w/ people who use drugs & respect their preferences, we argue using people-first strengths-based & inclusive language with care breaks down #DrugStigma & builds equitable values policies & practices

===[https://x.com/CarrieLWade/status/1829103064944410688 Carrie Wade]===
*Subject near and dear to my heart …. People in every area of drug research would benefit from reading, but particularly those in tobacco control and tobacco industry. None of us are off the hook.

=='''Examples: People Who Smoke'''==

===2022: [https://ash.org.uk/wp-content/uploads/2022/05/ASH-Housing-LIN-Smoking-and-Social-Housing-May-2022.pdf Smoking and social housing from LIN and ASH]===
*''' "People who smoke" '''are mentioned 16 times in this report. One example: "These particular examples also shine a light on the potential of e-cigarettes for people who smoke and live in social housing. Reviews of the evidence by the National Academies of Sciences, Engineering and Medicines in the US and the UK Committee on Toxicity have concluded that the relative risk of adverse health effects from e-cigarettes are likely to be substantially lower than from smoking. E-cigarettes have also been shown to be an effective aid for quitting, in clinical trials and at population level, with some evidence suggesting they are even more effective than traditional forms of nicotine replacement therapy, like patches and gum. They also appear to have been particularly valuable among groups who face higher levels of addiction and more barriers to quitting, for example among people experiencing homelessness and people with mental health conditions. Considered alongside the evidence from the ‘Swap to-Stop scheme, e-cigarettes therefore present a real opportunity to substantially benefit people who smoke and live in social housing."

===[https://www.canada.ca/en/health-canada/news/2021/05/health-canada-announces-funding-for-a-tobacco-cessation-project-to-mark-world-no-tobacco-day-2021.html Health Canada]===
*"Today, to mark World No Tobacco Day, the Honourable Patty Hajdu, Minister of Health, announced $3 million in funding for a national social marketing campaign to encourage '''people who smoke''' to quit."

===[https://www.cancer.org/healthy/stay-away-from-tobacco/e-cigarettes-vaping/what-do-we-know-about-e-cigarettes.html American Cancer Society]===
*"Some '''people who smoke''' choose to try e-cigarettes to help them stop smoking. Stopping smoking clearly has well-documented health benefits...People who have already switched completely from smoking to e-cigarettes should not switch back to smoking (either solely or along with e-cigarettes), which could expose them to potentially devastating health effects."

=='''Studies, Papers, Reports - Smoking (Stigma)'''==

===2023: [https://www.sciencedirect.com/science/article/pii/S0376871623012711 How has the brain disease model of addiction contributed to tobacco control?]===
*"Tobacco denormalisation deliberately encourages beliefs that people who smoke are selfish, unattractive, ‘addicts’, of ‘lower class.'" "Critics argue that this approach to tobacco denormalisation is discriminatory, stigmatises people who smoke, and may prevent smokers from seeking help to quit or be treated for tobacco-related diseases."
*"There is little evidence that the BDMA [brain disease model of addiction] has reduced the stigma suffered by people who smoke cigarettes." "Indeed, in many studies, people who smoke report experiencing significant stigma. Stigma has also arguably increased as cigarette smoking has become concentrated in the least educated and most socially disadvantaged groups in the populations of high-income countries."
*"In principle, public acceptance of a BDMA for smoking could have produced a more sympathetic response to people who smoke cigarettes, but survey evidence suggests that this has not happened. On the contrary, as population smoking prevalence has declined, the stigmatisation of smokers seems to have increased because smoking is concentrated among the most disadvantaged members of the population. Furthermore, the strategy of labelling people who smoke as “addicts” may increase the association between smoking and a spoiled identity. In principle, the BDMA could support policies that promote the use of less harmful forms of nicotine delivery to people who are unwilling or unable to quit smoking. In practice, however, it seems more likely to be used to justify bans on the sale of products that deliver nicotine in less harmful ways than combustible cigarettes, because these products can produce addiction."

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086928/ What low-income smokers have learned from public health pedagogy: A narrative inquiry]===
*Frohlich et al and others have suggested that public health educational messages may have the unintended consequence of marginalizing low-income smokers and unintentionally contributing to health disparities. Our study participants also point to healthcare professionals as an important group who may be contributing to these feelings. With this in mind, efforts to educate healthcare providers on how their actions may be perceived as judgmental or lacking in compassion about the effects of nicotine withdrawal are warranted.

===2020: [https://www.mdpi.com/1660-4601/17/12/4345/htm Stigma and Smoking in the Home: Parents’ Accounts of Using Nicotine Replacement Therapy to Protect Their Children from Second-Hand Smoke]===
*However, smoking prevalence remains disproportionally high in socioeconomically disadvantaged groups.
*Smoking stigma, particularly self-stigma, underpinned accounts, with two overarching themes: interplaying barriers and enablers for creation of a smoke-free home...
*Personal motivation to abstain or stop smoking empowered participants to reduce or quit smoking to resist stigma. For those struggling to believe in their ability to stop smoking, stigma led to negative self-labelling.
*Whilst denormalisation of smoking has been a useful public health tool for reducing smoking rates in the UK, it is arguable that this can lead to unhelpful stigmatisation of already vulnerable disadvantaged groups.

===2019: [https://www.jto.org/article/S1556-0864(19)30813-5/fulltext ES13.05 Stigma and Impact of Tobacco Control Policy]===
*The stigma reduces the funding available for lung cancer research. In the US, federal funding for lung cancer research per lung cancer death is only 15% of the funding amount for breast cancer per breast cancer death.
*In a Global Lung Cancer Coalition survey, one in five people (21%) agreed with the statement that they have less sympathy for people with lung cancer than for people with other types of cancer.
*Stigmatization of smokers has the greatest impact on the socioeconomically deprived, the disadvantaged populations. These populations have the highest prevalence of smokers and encounter the stigma of their race or disadvantage (poverty, disability, sexual preference, behavioral health etc.) in addition to the stigma associated with smoking.
*This stigmatization leads people who smoke to be less likely to seek medical care when they have symptoms, more likely to lie about their smoking, more likely to be refused access to care including curative surgery for early stage lung cancer unless they quit smoking, less likely to be offered smoking cessation help if they are uncomfortable disclosing their smoking status due to stigma and bias from their healthcare professional.

===2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625812/ DOES IT HELP SMOKERS IF WE STIGMATIZE THEM? A TEST OF THE STIGMA-INDUCED IDENTITY THREAT MODEL AMONG U.S. AND DANISH SMOKERS]===
*"Thus, stigmatization led smokers toward emotional, cognitive, and attitudinal reactions that might make them less likely to quit."

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297009/ Smoking-Related Stigma: A Public Health Tool or a Damaging Force?]===
*This study suggests that perceived smoking-related stigma may be associated with more quit attempts, but less successful quitting among smokers. It is possible that once stigma is internalized by smokers, it may function as a damaging force.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319257/ Internalized smoking stigma in relation to quit intentions, quit attempts, and current e-cigarette use]===
*Consistent with previous research we have found that smokers’ who reported greater feelings of stigmatization about their smoking were more likely to report having made recent quit attempts and report a stronger intention quit smoking in the future.
*It is also important to recognize the potential negative consequences associated with stigmatizing smokers, who may seek ways to evade stigma by segregating themselves into groups accepting of smoking and perhaps fostering the development of fatalistic attitudes about their ability to change their smoking behavior, which make quitting smoking harder to accomplish. Thus, behavioral interventions for smoking cessation might include addressing stigma-related issues as part of the quitting process.

===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675843/ Validity and Reliability of the Internalized Stigma of Smoking Inventory: An Exploration of Shame, Isolation, and Discrimination in Smokers with Mental Health Diagnoses]===
*In addition to the health disparities experienced by smokers, psychosocial factors such as smoking stigma can cause additional strain on health, and may thwart positive behavior change. Smoking stigma can be defined as a social process by which exclusion, rejection, blame or devaluation occurs,7 in this case related to smoking or being identified as a smoker. Stigma can be categorized as: 1) internally-focused self-stigma resulting from the internalization of public stigma and characterized by statements about the individual's worth, e.g., “I am worth less because I smoke”; 2) perceived or felt stigma, which is an awareness of devaluation or stereotype in work, social, and everyday situations, and includes fear of being stigmatized, experiencing external blame, and social isolation; or 3) enacted stigma, which refers to acts of discrimination perpetrated on stigmatized individuals.
*We would consider, however, efforts to induce stigma as abjectly wrong and avoidable. Instead, treatment engagement strategies could emphasize stigma-reduction as an ancillary benefit – i.e., messaging that quitting smoking can reduce stigma, rather than messaging aimed at increasing stigma to induce quitting.

===2012 [https://digitalscholarship.unlv.edu/jhdrp/vol5/iss1/2/ Self-stigma, Stress, and Smoking among African American and American Indian Female Smokers: An Exploratory Qualitative Study]===
*However, continued smoking was also a source of negative emotion, as women felt shame, guilt and low self-esteem over their inability to quit, which was perceived by some as indicative of weakness. These negative self-perceptions are consistent with stigmatized views of smokers held by the public. Women also expressed feelings of defiance about their smoking despite pressure to quit and identified external factors which contributed to their inability to quit. The negative emotions, self-stigma and shame experienced by low income American Indian and African American women smokers may contribute to continued smoking and disrupt quit attempts. Additional research is needed in order to develop effective tobacco cessation interventions for this group.

===2009: [https://asara.org.ar/wp-content/uploads/2014/08/IX-JORNADAS-INTERNACIONALES-stigma-chapter.pdf The Psychological Effects of Social Stigma: Applications to People with an Acquired Hearing Loss]===
*To various extents, people who smoke are devalued as individuals and discredited as a member of society; they are stigmatized.

===2008: [https://tobaccocontrol.bmj.com/content/17/1/25 Markers of the denormalisation of smoking and the tobacco industry]===
*Results: We caution about some important negative consequences arising from the stigmatisation of smokers. (note: paper gives several examples)

===2008: [https://www.tandfonline.com/doi/abs/10.1080/09581590802687358 Tobacco control and the inequitable socio-economic distribution of smoking: smokers’ discourses and implications for tobacco control]===
*[https://sci-hub.se/10.1080/09581590802687358 Full Study on Sci-Hub]
*Few low SES smokers questioned their smoking status, instead framing smoking as a ‘fact of life’. However, there was also a clear sense that tobacco control, and its adherents, are contributing to a sense of stigmatised identity for these smokers.

===2006: [https://onlinelibrary.wiley.com/doi/abs/10.1002/casp.896 Pollution, peril and poverty: a British study of the stigmatization of smokers]===
*Stigma is a mark of social disgrace that arises within social interaction (Goffman, 1963). It disqualifies bearers of the mark from full social acceptance.
*The results suggest that British smokers are identified via a negative aesthetic marker, consisting of smell and appearance. Like all stigmatized marking, they are not assessed merely at a cognitive level, but emotionally too (Jones et al., 1984). Non-smokers report repulsion, dislike, irritation, sickness and, most often, disgust in the face of them.
*[https://sci-hub.st/10.1002/casp.896 Full Study on Sci-Hub]

=='''Articles, Websites, Blogs - Smoking/Nicotine (Stigma)'''==

===2023: [https://filtermag.org/stigma-nicotine-research-newhouse/ Watch: Stigma Hampers Recruitment for Nicotine Research]===
*“The political climate and the concerns of the anti-tobacco and anti-smoking advocacy groups has made it harder to do this kind of research,” he explained. “It has impacted our ability to recruit people to our studies.”

===2022: [https://filtermag.org/smoking-stigma-harm-reduction/ The Stigmatization of Smoking Is Not Harm Reduction]===
*Instead of stigma, we need an open and unfettered discussion.

===2015: [https://www.fredhutch.org/en/news/center-news/2015/11/smoking-stigma-backfires-hurts-efforts-quit.html Smoking stigma can hurt efforts to quit]===
*Public health campaigns that stigmatize smoking can backfire, according to a study published Monday, leading some people to become so angry and defensive that they refuse to quit and others feeling so bad about themselves that they give up trying.
*Smokers reported feeling shame, guilt and embarrassment for their smoking behavior and used words such as “leper,” “outcast,” “bad person,” “low-life” and “pathetic” to describe themselves, the study found. These feelings increased after failed attempts to quit smoking.

=='''Studies, Papers, Reports, Articles, Blogs, Videos, etc. - Stigma, Smoking, and Lung Cancer'''==

===2025: [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2841677 Age-Based Screening for Lung Cancer Surveillance in the US]===
*"Unlike risk-based lung cancer screening focused exclusively on tobacco smoking, universal breast and colorectal cancer programs have simplified access and increased participation.28 Risk-specific guidelines may deter participation by implying lifestyle blame or creating eligibility confusion, compounded by stigma."

=== 2025: Article: [https://archive.ph/hvzZd The hidden reason lung cancer screening is not working]===
*By: Lisa Carter-Bawa, Ph.D., M.P.H., N.P.

===2025: IASLC Podcast: [https://www.iaslc.org/iaslc-news/lung-cancer-considered/please-dont-tell-my-family-stigma-and-lung-cancer “Please Don’t Tell My Family”: Stigma and Lung Cancer]===
*Featuring: Narjust Florez MD - Lisa Carter-Bawa PhD, MPH, APRN - Jamie L. Studts PhD

===2023: Article: [https://medicalxpress.com/news/2023-09-stigmatization-smoking-related-diseases-barrier-problem.html Stigmatization of smoking-related diseases is a barrier to care, and the problem may be on the rise]===
*"The study, conducted by a team of researchers led by Nathan Harrison, a behavioral scientist and Ph.D. student from Flinders University, in Australia, aimed to identify and synthesize existing interventions to combat stigma associated with lung cancer and smoking-related respiratory diseases, including chronic obstructive pulmonary disease (COPD)."

===2023: Op-Ed: [https://filtermag.org/lung-cancer-vaping-misinformation/ Stigma and Misinformation Maintain the Devastating Toll of Lung Cancer]===
*By: Skip Murray

===2022: [https://www.sciencedirect.com/science/article/pii/S2772628222000103 Reducing stigma triggered by assessing smoking status among patients diagnosed with lung cancer: De-stigmatizing do and don't lessons learned from qualitative interviews]===
*Patients expressed clear preferences for CCPS to refrain from using judgmental labels when assessing smoking history, including a preference for questions such as ''' “have you smoked cigarettes in the past 30 days” rather than “are you a smoker?” '''. This perspective is consistent with the broader clinical efforts and dissemination of resources to reduce illness-related stigma through the increased use of person-first language and other bias-free language in clinical care and research. [emphasis added]

===2021: [https://www.lungcancercoalition.org/wp-content/uploads/2021/03/Great-Britain-national-data-pack-FINAL.pdf Great Britain: symptom awareness and attitudes to lung cancer Findings from a global study]===
*One in four (25%) people in the UK agreed that they have less sympathy for people with lung cancer than other forms of cancer. Globally, one in five (21%) people agreed that they have less sympathy for people with lung cancer than other forms of cancer.

===2018: [https://pubmed.ncbi.nlm.nih.gov/29800746/ Multilevel Opportunities to Address Lung Cancer Stigma across the Cancer Control Continuum]===
*"Attention to the robust causal connection between smoking and lung cancer, although crucial for tobacco control, may have unintended consequences that generate blaming responses and biased negative perceptions toward patients with lung cancer..."

===2018: Article: [https://connection.asco.org/do/helping-patients-face-lung-cancer-stigma “Please Don’t Tell My Family!”: Helping Patients Face Lung Cancer Stigma]===
*By: Narjust Florez, MD, FASCO

===2017: [https://journalofethics.ama-assn.org/article/decreasing-smoking-increasing-stigma-anti-tobacco-campaigns-public-health-and-cancer-care/2017-05 Decreasing Smoking but Increasing Stigma? Anti-tobacco Campaigns, Public Health, and Cancer Care]===
*"Public health researchers, mental health clinicians, philosophers, and medical ethicists have questioned whether the public health benefits of large-scale anti-tobacco campaigns are justified in light of the potential for exacerbating stigma toward patients diagnosed with lung cancer. Although there is strong evidence for the public health benefits of anti-tobacco campaigns, there is a growing appreciation for the need to better attend to the unintended consequence of lung cancer stigma. We argue that there is an ethical burden for creators of public health campaigns to consider lung cancer stigma in the development and dissemination of hard-hitting anti-tobacco campaigns. We also contend that health care professionals have an ethical responsibility to try to mitigate stigmatizing messages of public health campaigns with empathic patient-clinician communication during clinical encounters."

===2015: [https://pubmed.ncbi.nlm.nih.gov/25736473/ Lung cancer stigma as a barrier to medical help-seeking behavior: Practice implications]===
*"Findings support an association between lung cancer stigma and delayed medical help-seeking behavior. Therefore, lung cancer stigma is a potential barrier to timely medical help-seeking behavior in lung cancer symptoms, which can have important patient outcome implications."

===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634635/ Lung Cancer Stigma, Anxiety, Depression and Quality of Life]===
*Regardless of smoking status, lung cancer patients have reported stigmatization from clinicians, family members and friends due to strong associations between smoking and lung disease.
*The results of this study confirm our previous findings that LCS [lung cancer stigma] is positively correlated with anxiety and depression and negatively correlated with QOL [quality of life].

===2012: [https://link.springer.com/article/10.1186/1471-2407-12-184 A systematic review of the impact of stigma and nihilism on lung cancer outcomes]===
*"There is qualitative evidence that from the patients’ perspectives public health programs contribute to stigma about lung cancer and this was supported by published commentary."

=='''Studies, Papers, Reports - Employment and/or Insurance (People Who Use Nicotine)'''==

===2024: [https://econtent.hogrefe.com/doi/10.1027/1866-5888/a000352 When Job Opportunities Go Up in Smoke]===
*"In the present study, 400 Canadian and US hiring professionals evaluated a candidate’s resume and then cybervetted their social media page which disclosed their gender and smoking status (i.e., cigarette smoker, vaper, or nonsmoker). Revised evaluations post-cybervetting were lower for applicants discovered as smokers and vapers than for nonsmokers, but vapers were perceived as negatively as smokers."

===2023: [https://www.virginiamercury.com/2023/03/14/youngkin-says-he-will-sign-legislation-ending-higher-insurance-premiums-for-tobacco-users/ Youngkin says he will sign legislation ending higher insurance premiums for tobacco users ]===
*“Tobacco users tend to have lower incomes, which is often a barrier to coverage,” Barber said. “Charging them more to access the care they need … is harmful and inequitable. The VPHA is cautiously optimistic that this barrier will go away, and people will be able to afford quality coverage and get the care they need for their tobacco use and beyond.”

===2020: [https://www.sciencedirect.com/science/article/pii/S2352827320302354 Occupying multiple stigmatized identities: Smoking and unemployment stigmas among the unemployed]===
*Study findings support the need to examine stigma – in particular, multiply occupied stigmas – as an important social determinant of health. Stigma may relate to job-seekers’ employment opportunities, efforts to quit smoking, and physical and mental health. Greater attention to multiply occupied stigmas and experimental investigations to identify novel strategies to reduce stigma are warranted.
*In addition to the health and financial harms associated with smoking, the “smoker” label today may also carry stigma
*The association of smoking and unemployment stigmas with depressive symptoms is consistent with prior findings of an association between lung cancer stigma and the severity of depressive symptoms

===2018: [https://psycnet.apa.org/record/2017-40480-001 A qualitative review of tobacco research related to public and structural stigma.]===
*Our review found that some smokers experience self-stigma such as self-loathing and shame as a result of public stigma. The few studies on structural interventions suggest that they affect some smokers in counterproductive ways, such as eliciting defiance and/or prompting public and self-stigma.
*Importantly, no studies examine stigma-related impact of newer structural interventions, such as higher insurance premiums or worksite policies to employ only nonsmokers.
*'''To advance the field, it will be critical to pinpoint whether, when, and how denormalization becomes stigmatization.''' [emphasis added]
*Removing the stigmatizing aspects of existing approaches, and creating new interventions that avoid stigmatizing smokers, may help further enhance the reach and effectiveness of tobacco control.

===2017: [https://www.cambridge.org/core/journals/journal-of-law-medicine-and-ethics/article/abs/stigmatizing-the-unhealthy/A5459EB669E1C69C9326C13915D6E379 Stigmatizing the Unhealthy]===
*[https://sci-hub.se/10.1177/1073110517750582 Sci-Hub (full paper)]
*The very fact that the Affordable Care Act moved away from health status-based rating in the individual market, with conspicious exceptions for tobacco use and wellness program participation, is telling. The ACA then suffers from an internal tension. On one hand, its supporters framed it as “a civil rights bill for the sick.” On the other, despite eliminating health insurance practices that explicitly disadvantage people based on health, the ACA permits — even encourages — health insurers to charge more to people who use tobacco. Pursuant to the tobacco surcharge, an insurer can opt to charge a tobacco user up to fifty percent more for the same health plan. While many health insurance companies may not opt to charge the full penalty, the ones that do could price out smokers and other tobacco users.
*It then comes as no real surprise that the Affordable Care Act’s tobacco surcharge may actually backfire, leading people to drop health insurance rather than to quit smoking. Given both the intervention’s ineffectiveness and its lack of a clear justification for regulating tobacco use and no other health status, we propose that singling out tobacco users may be the result of animus.
*The tobacco surcharge singles out smokers and other tobacco users, thus communicating
**(1) that tobacco use has social meaning as a category,
**(2) that using tobacco is socially undesirable,
**(3) that classifying people based on their tobacco use is acceptable, and
**(4) that tobacco users should face disadvantage in the form of a heightened premiums.
*In other words, the tobacco surcharge mirrors the process of stigmatization. Thus, even if the tobacco surcharge is not driven by animus against smokers, the ACA could lay the foundation for stigmatizing tobacco users.
*Smokers face similar kinds of regulation outside health insurance. Some employers refuse to hire nicotine users of any kind. As one set of authors explain, workplace bans, “by sanctioning discrimination, abrogate smoker’s rights as ‘ordinary citizens’ by placing ‘them’ in a category that separates smokers from ‘us’(non-smokers).

===2016: [https://researchonline.stthomas.edu/esploro/outputs/graduate/Smoking-Cessation-and-the-Role-of/991015131652903691 Smoking Cessation and the Role of Stigma: A Systematic Review]===
*What emerged from this review is current anti-smoking campaigns are not effective for smokers who are living in poverty. These findings suggest that anti-smoking campaigns need to limit stigma and build programs that are effective for all socio-economic classes.
*Anti-smoking campaigns have been used for the last three decades, and while there has been a decrease in smokers across the US, the number of smokers living in poverty has remained relatively unchanged. The research points to the use of stigma as a possible reason for smokers who are living in poverty to not stop smoking. The use of stigma to help a population, who may be stigmatized for multiple reasons, has shown through the research, to be a poor tool in moving them towards a smoke free life. The use of stigma in public health campaigns may lead to making things worse for smokers who live in poverty through discrimination in hiring policies and other unintended consequences.

===2016: [https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2513450 Likelihood of Unemployed Smokers vs Nonsmokers Attaining Reemployment in a One-Year Observational Study]===
*Smokers had a lower likelihood of reemployment at 1 year and were paid significantly less than nonsmokers when reemployed.

===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630105/ The Downside of Tobacco Control? Smoking and Self-Stigma: A systematic review]===
*While there is evidence that internalizing smoking stigma may prompt some individuals to quit smoking, this review also suggests that smoking self-stigma can have profoundly negative consequences for some smokers and may make quitting more difficult.
*Currently, there may be an overreliance on strategies which focus on negative reinforcement including both strategies to change smoking norms and increase smoke-free public spaces as well as more structurally stigmatizing policies such as basing hiring decisions and health insurance costs on smoking status.

===2013: [https://www.nejm.org/doi/full/10.1056/NEJMp1301951 The Ethics of Not Hiring Smokers]===
*Many health care organizations, such as the Cleveland Clinic and Baylor Health Care System, and some large non–health care employers, including Scotts Miracle-Gro, Union Pacific Railroad, and Alaska Airlines, now have a policy of not hiring smokers — a practice opposed by 65% of Americans, according to a 2012 poll by Harris International. We agree with those polled, believing that categorically refusing to hire smokers is unethical: it results in a failure to care for people, places an additional burden on already-disadvantaged populations, and preempts interventions that more effectively promote smoking cessation.

===2008: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006698/ Smoking and the emergence of a stigmatized social status]===
*Structural forms of discrimination perpetrated against smokers and former smokers (e.g., company policies against hiring smokers) are also related to smoker-related stigma.

=='''Articles, Websites, Blogs - Employment and/or Insurance (People Who Use Nicotine)'''==

===2023: [https://economictimes.indiatimes.com/wealth/insure/life-insurance/you-can-save-80-on-your-term-life-insurance-premium-if-you-quit-smoking-when-and-how-to-buy-it/articleshow/102713832.cms You can save up to 80% on your term life insurance premium if you quit smoking; when and how to buy it]===
*"How do most life insurance companies define 'smoker'? Usually, life insurance companies use very specific questions to find out whether you are a smoker or not. "The insurance companies consider an individual as a smoker if they take nicotine in any form like bidi, cigarettes, cigars, hookahs, chew tobacco, etc," says Pankaj Goenka, Assistant Vice-President & Head-B2B Business, Insurance Dekho. Even if you use a nicotine patch or gum, the insurer can classify you as a smoker."

===2020: [https://filtermag.org/u-haul-nicotine-policy/ U-Haul’s Hateful Policy of Barring Nicotine Users From Employment]===
*At the turn of the year, U-Haul announced that starting in February, they will “decline job applicants who are nicotine users” in the 21 states* where it’s legal to do so. And it doesn’t matter if the nicotine comes from a cigarette, a patch, gum or a vape.

===2019: [https://www.foxnews.com/health/ohio-citys-ban-on-hiring-smokers-vapers-could-be-slippery-slope-some-fear Ohio city's ban on hiring smokers, vapers could be 'slippery slope,' some fear]===
*More bad news for smokers and vapers: The city of Dayton, Ohio, says it will no longer hire anyone who uses nicotine or tobacco.

===2014: [https://web.archive.org/web/20201128142523/https://www.forthealthcare.com/wp-content/uploads/2014/06/smoking-ban-for-employees.pdf Smoking Ban for New Hires Spread Across the United States]===
*" These new policies essentially treat cigarettes like illegal narcotics. Applications now explicitly warn of “tobacco-free hiring,” job seekers must submit to urine tests for nicotine, and new employees caught smoking face termination."
*"Federal laws allow nicotine-free hiring because they don't recognize smokers as a protected class. There’s no data on how many U.S. businesses won't hire smokers, but the trend appears strongest with hospitals."

===2013: [https://www.nejm.org/doi/full/10.1056/NEJMp1303632 Conflicts and Compromises in Not Hiring Smokers]===
*"These policies engender controversy, and we recognize that they risk creating or perpetuating injustices. One set of concerns arises from the fact that tobacco use is more concentrated in groups with lower socioeconomic status. Hospitals do better than most institutions at creating employment and advancement opportunities for disadvantaged populations. So even though most members of lower socioeconomic groups do not use tobacco, and even though anti-tobacco hiring policies are not intended to reduce jobs for these populations, they are likely to do so inadvertently, at least somewhat."

===2011: [https://www.nytimes.com/2011/02/11/us/11smoking.html Hospitals Shift Smoking Bans to Smoker Ban]===
*Smokers now face another risk from their habit: it could cost them a shot at a job.

===2005: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309686/ WHO will not hire smokers]===
*"Smokers will no longer be eligible for employment at the World Health Organization, the agency has announced. Effective immediately, all job applicants will be asked if they smoke, and if so, whether they are willing to quit. The application process will be terminated in the case of smokers who refuse to stop."
*"The rule will extend to users of chewing or snuff tobacco."

='''"Relapse"'''=
*Suggested words to use instead of relapse(d): recurrence (appears to be the most widely used), return, resume (resumption), slip, lapse, (use) episode, substance use (no strings attached to current, former, daily, random), revert, recent use... these and other suggestions can be found on this question posed on [https://twitter.com/imaracingmom/status/1519975031778033665 Twitter] in the comments.

==Articles, Websites, Blogs - Relapse==

===2019: [https://denicarise.medium.com/its-time-to-quit-using-stigmatized-words-like-relapse-87c1ab14fa56 It’s Time to Quit Using… Stigmatized Words Like Relapse]===
*Much of society associates the term “relapse” with failure because of an antiquated and baseless condemnation of individuals with substance use disorder who do not become “cured” with their first treatment. Very often, there is immediate judgment.
*I propose that if we want to help erase stigma, we choose to use the word recurrence rather than relapse. “Recurrence of substance use disorder” creates a more accurate connotation, one that is more consistent in the medical world.
*Our language activates implicit cognitive scripts that give meaning to what we try to convey and communicate.

='''Use of Stigma/Shame to Prevent Initiation or to Encourage Cessation'''=

===1993: [https://tobaccocontrol.bmj.com/content/tobaccocontrol/2/4/271.full.pdf Animals and butts: Minnesota's media campaign against tobacco]===
*Information about the campaign from the late 80's and early 90's. (Using language like "stupid," "silly," and "butts.")
*[https://twitter.com/grayjaynine/status/1744505202416529743 Tweet] with photo of animals smoking poster.

===1993: [https://www.latimes.com/archives/la-xpm-1993-11-17-vw-57872-story.html Wrong Message? : Smoking: As part of the Great American Smokeout on Thursday, the American Cancer Society’s posters take a no-holds-barred approach to steering schoolchildren away from cigarettes. But some O.C. educators are concerned that the posters are too blunt.]===
*"Some educators were wary about “whether the materials were appropriate for use in the schools."

='''Lessons Learned: Substances, Alcohol, Incarceration, Illnesses, Disabilities, Mental Health, Weight, etc.'''=

=='''Studies, Papers, Reports - Language/Stigma'''==

===2024: [https://onlinelibrary.wiley.com/doi/full/10.1002/jaoc.12137 Person-first language and addiction literature: The presence of labeling and emotional language in counseling articles]===
*"The purpose of this study was to determine the rate and frequency of labeling language, emotional language, and person-first language (PFL) toward individuals with substance use disorders and addictions in articles published in 24 counseling journals. Of the 249 articles reviewed, 61.04% did not fully adhere to PFL, while 34.54% included labeling language and 51.41% included emotional language. A significant positive correlation was found between the use of labeling language and emotional language. Implications for practicing counselors, counselor educators, and researchers are provided. We advocate for the use of PFL toward those with addictions in published works and in conversations."

===2024: [https://www.sciencedirect.com/science/article/pii/S2772724624000210 Substance use stigma: A systematic review of measures and their psychometric properties]===
*"Stigma, defined as societal labeling and mistreatment based on perceived differences (Link and Phelan, 2001) leads to a divisive “us” versus “them” dynamic that leads to status loss in a context of power dynamics. Substance use stigma (SUS) involves negative stereotypes and discrimination toward people that use substances, which results in limiting their access to needed resources and impeding wellbeing (Livingston et al., 2012). Stigma is pervasive in society and based out of moral judgments that substance use is bad or wrong (Room, 2005)."
*"SUS significantly hinders treatment and education, adding to the burden carried by people with substance use disorders (Keyes et al., 2010, Kulesza et al., 2013). It limits access to treatment through underfunding of substance use treatment services (Saloner et al., 2014, Zemore et al., 2021, Calabrese et al., 2016, Luoma, 2010) and creates barriers to reintegrating into communities (Neale et al., 2011)."

===2023: [https://www.sciencedirect.com/science/article/abs/pii/S0889855323000869 Language Frames and Shapes the Response to Obesity]===
*Shaping a more effective response to obesity can start with the careful use of language that frames obesity in ways that are person centered, scientifically accurate, easily understood, and limits risk of bias.

===2023: [https://journals.lww.com/journaladdictionmedicine/Abstract/9900/The_Incidence_and_Disparities_in_Use_of.150.aspx The Incidence and Disparities in Use of Stigmatizing Language in Clinical Notes for Patients With Substance Use Disorder]===
*"The majority of patients with substance-related diagnoses had at least one note containing SL. There were also several patient characteristic disparities associated with patients having SL in their notes. The work suggests that more clinician interventions about use of SL are needed."

===2022: [https://assets.pubpub.org/jcnh8c3v/71666271791414.pdf Guidelines on Inclusive Language and Images in Scholarly Communication]===
*Coalition for Diversity and Inclusion in Scholarly Communications
*In most cases it is preferable to emphasize the person over the attribute. For example, “person with cancer” instead of “cancer patient”, “man in prison” instead of “inmate.” Emphasizing the attribute can reduce the person to a label and dehumanize them.

===2022: [https://pubmed.ncbi.nlm.nih.gov/35727299/ Why language matters in alcohol research: Reducing stigma]===
*The results of a separate manual search (n = 110) on the Wiley Online Database showed that approximately 30% of articles used the term "alcoholic" in a stigmatizing manner.
*Stigmatizing language can perpetuate negative biases against people with alcohol use disorder. We encourage researchers to shift away from language that maintains discriminatory conceptions of alcohol use disorder. Reducing stigma has the potential to increase rates of treatment seeking and improve treatment outcomes for individuals with alcohol use disorder.

===2021: [https://www.nature.com/articles/s41386-021-01069-4.epdf Choosing appropriate language to reduce the stigma around mental illness and substance use disorders]===
*"The words we use to describe mental illnesses and substance use disorders (addiction to alcohol and other legal and illegal drugs) can impact the likelihood that people will seek help and the quality of the help they receive. Research indicates that stigma—negative attitudes toward people based on distinguishing characteristics—contributes in multiple ways to poorer health outcomes; consequently, it has been identified as a critical focus for research and interventions"
*"Stigma is particularly difficult to eliminate, even with educational and other interventions, and carefully considered language is only one part of addressing it. But it is also one of the most immediate ways in which researchers and others who communicate about stigmatized conditions can effect change."

===2021: [https://www.ama-assn.org/system/files/ama-aamc-equity-guide.pdf Advancing Health Equity: Guide to Language, Narrative and Concepts]===
*This guide is intended to raise questions about language and commonly used phrases and terms, with the goal of cultivating awareness about dominant narratives and offering equity-based, equity-explicit, and person-first alternatives.
*In these simple examples, we can start to recognize the power of language to frame our thinking; equity-focused, person-first language seeks to center the lived experience of people and communities without reinforcing labels, objectification, stigmatization and marginalization.
*This guide is not intended to be a definitive and all-encompassing instruction manual. Instead, it was written (with humility) to stimulate heightened awareness and dialogue. We offer this guide as a tool, knowing that efforts to nurture change in contentious spaces requires courage and commitment. Undermining systemic oppression and the dominant narratives that sustain them will not happen by chance. Reclaiming and promoting a social justice narrative will require intentional and collective action.

===2021: [https://pubmed.ncbi.nlm.nih.gov/34749889/ Weight Bias and Stigma: Impact on Health]===
*"Weight bias and stigma exist in a variety of realms in our society (media, education, employment, and health care), and unfortunately many view it as a socially acceptable form of discrimination. Patients with obesity often avoid scheduling appointments for health promotion visits and routine care due to perceived weight bias and stigma from their health care provider."

===2021: [https://pubmed.ncbi.nlm.nih.gov/34217277/ Media framing of emergency departments: a call to action for nurses and other health care providers]===
*"Two overarching themes were found. First, in ED-related media that portrays health care needs of people experiencing health and social inequities, messaging frequently perpetuates stigmatizing discourses..."

===2020: [https://www.canada.ca/en/public-health/services/publications/healthy-living/primer-reduce-substance-use-stigma-health-system.html A Primer to Reduce Substance Use Stigma in the Canadian Health System]===
*Substance use stigma is prevalent throughout the health system and contributes to poorer quality of care and negative health outcomes.
*Creating a stigma-free health system will require collaborative action and sustained commitment of key players across the health system.
*Efforts to reduce substance use stigma within the health system must also acknowledge and address intersecting stigmas, including through initiatives not traditionally labelled as “anti-stigma interventions”.

===2019: [https://gh.bmj.com/content/4/5/e001911 Why we should never do it: stigma as a behaviour change tool in global health]===
*Shame-induced stigma most damages those already vulnerable, reinforcing health disparities.
*Global health use of shaming tactics can inadvertently worsen health-damaging stigma, especially for those with the least power.
*These effects, that drive additional health disparities and suffering, are difficult to prevent.
*Ethically and practically, stigma should never be deployed as a global health tool because the effects are often both unavoidable and invisible to outsiders.

===2019: [https://www.cpha.ca/sites/default/files/uploads/resources/stbbi/language-tool-e.pdf LANGUAGE MATTERS Using respectful language in relation to sexual health, substance use, STBBIs and intersecting sources of stigma]===
*Words matter. Certain words can make people or groups feel excluded, and can also convey stereotypes, expectations or limitations based on a person’s identity...
*Language changes. As societal values change over time, so does the language that is considered acceptable...
*Mindset matters. Be open and empathetic, and encourage others to do the same...
*Person first. Use ‘person first’ language: language that prioritizes someone’s identity and individuality above whatever other characteristic you might be describing...
*Be inclusive. Try and use language that is as inclusive as possible to reflect the known or unknown diversity of your audience. For example, instead of using the terms husband or wife when unsure of the sexual orientation and/or marital status of who you are speaking with, use the term ‘partner.’ Similarly, when referring to a group of people, try ‘folks’ instead of ‘guys.’
*Be specific. Use language that is consistent with how a person identifies and is comfortable for them...
*Be critical. Before introducing or describing someone based on personal characteristics (such as race, gender identity, (dis)ability, use of substances, etc.), ask yourself whether it is relevant and necessary to do so...

===2019: [https://pubmed.ncbi.nlm.nih.gov/30945955/ Biased labels: An experimental study of language and stigma among individuals in recovery and health professionals]===
*Results provide further evidence that previously identified stigmatizing labels have the potential to influence medical care and medical practitioner perceptions of individuals with substance use disorders and should be avoided.

===2018: [https://www.tandfonline.com/doi/full/10.1080/1068316X.2017.1421640 Why call someone by what we don't want them to be? The ethics of labeling in forensic/correctional psychology]===
*As highlighted in the Publication Manual of the American Psychological Association, many labels can be perceived as pejorative and stigmatizing.
*We can continue to model stigmatizing and pejorative language that politicians and the media will no doubt take one step further, or we can start changing the way we talk about the men, women and young people we work with and research, in the hope that they too will change.

===2018: [https://pubmed.ncbi.nlm.nih.gov/29743656/ Considerations for substance-use disorder language: cultivating a shift from 'addicts in recovery' to 'people who thrive']===
*"We consider the role language plays in the SUD treatment field and how the language and concepts the words convey keep individuals from growing through and past the SUD. We argue that a new understanding calls for a shift in language among providers of SUD care in which the culture of SUD treatment begins to emphasize 'thriving' rather than 'recovery' from SUDs."

===2018: [https://pubmed.ncbi.nlm.nih.gov/29913324/ Substance use, recovery, and linguistics: The impact of word choice on explicit and implicit bias]===
*The general public, treatment professionals, and healthcare professionals have been found to exhibit an explicit negative bias towards substance use and individuals with a substance use disorder (SUD).
*Results support calls to cease use of the terms "addict", "alcoholic", "opioid addict", and "substance abuser". Additionally, it is suggested that "recurrence of use" and "pharmacotherapy" be used for their overall positive benefits. Both "medication-assisted recovery" and "long-term recovery" are positive terms and can be used when applicable without promoting stigma.

===2017: [https://publications.aap.org/pediatrics/article/140/6/e20173034/38277/Stigma-Experienced-by-Children-and-Adolescents Stigma Experienced by Children and Adolescents With Obesity]===
*Weight stigma is often propagated and tolerated in society because of beliefs that stigma and shame will motivate people to lose weight. However, rather than motivating positive change, this stigma contributes to behaviors such as binge eating, social isolation, avoidance of health care services, decreased physical activity, and increased weight gain, which worsen obesity and create additional barriers to healthy behavior change. Furthermore, experiences of weight stigma also dramatically impair quality of life, especially for youth.

===2015: [https://www.sciencedirect.com/science/article/pii/S1059131115002435 How does the label “epileptic” influence attitudes toward epilepsy?]===
*Our results verify that just by placing the word “person” as the first one in the label we use, we can, at least partially, avoid the stigma induced when “epileptic” – as being the main determinant of that certain person – is used.

===2014: [https://iep.utm.edu/pejorati/ Pejorative Language]===
*Some words can hurt. Slurs, insults, and swears can be highly offensive and derogatory.

===2013: [https://journals.sagepub.com/doi/10.1177/1078390313489729 Championing Person-First Language: A Call to Psychiatric Mental Health Nurses]===
*This article champions the use of person-first language as a foundation for recovery-oriented practice and enhanced collaborative treatment environments that foster respect, human dignity, and hope.

===2013: [https://pubmed.ncbi.nlm.nih.gov/24621488/ Stigmatizing harm reduction through language: a case study into the use of "addict" and opposition to supervised injection sites in Canada]===
*"The use of labels is one way stigma is perpetuated by eliciting the label's stereotyped narratives onto an individual or group. Within harm reduction discourse, the word "addict" can have detrimental effects on how the public perceives people experiencing addiction and their deservingness of pragmatic services. This article aims to draw attention to the inattention we give "addict" in language and explain how its routine use in society acts to perpetuate addiction stigma. Using the example of supervised injection site opposition in Canada, the use of "addict" is used as a way to understand how stigma through language works to impede the expansion of harm reduction initiatives."

=='''Articles, Websites, Blogs - Language/Stigma'''==

===2024: [https://shameandmedicine.org/what-is-the-difference-between-shame-and-stigma/ What is the Difference Between Shame and Stigma?]===
*Identifying a condition as ‘stigmatising’ can show us how living with this condition can lead to negative social experiences such as discrimination, judgement, social exclusion, vilification, ostracism, labelling, loss of status, prejudice, unfair treatment, among others.
*It is important to understand shame because it is shame that drives behaviour and decision-making, and in healthcare contexts, shame can easily lead to disengagement, non-disclosure, lying, withdrawal and avoidance.

===2023: [https://www.apaservices.org/advocacy/news/addiction-related-federal-agencies Names of addiction-related federal agencies are changing]===
*Research has shown that reducing stigma makes it more likely that affected substance users will enter and maintain treatment.

===2023: [https://filtermag.org/samhsa-abuse-budget/?utm_source=twitter&utm_medium=social&utm_campaign=filter SAMHSA Eyes Budget Boost—and Cutting “Abuse” From Its Name]===
*“Abuse” is an ugly word. “Child abuse,” “sexual abuse,” “physical abuse,” “emotional abuse,” “domestic abuse.” And then, of course, there’s “substance abuse.”But one of those things is not like the others: In all of the other types of abuse, there is a perpetrator who is harming a victim.

===2022: [https://filtermag.org/drug-use-stigma/ Stigmatizing Drug Use Is Killing Us, But Why Is It So Hard to Stop?]===
*"Harm reduction at its core is a strategy against stigma. Giving people the space and freedom to manage their own health without judgment or coercion is a core component. Harm reduction is not just a strategy to minimize the risks of drug use, but a philosophy for self-care and community care that promotes compassion, openness and practical knowledge that can improve and save lives."

===2021: [https://peoplefirstcharter.org/ People First Charter]===
*The People First Charter launched in July 2021, during the Berlin International AIDS Society Conference, to promote person first HIV & Sexual Health language.
*Language matters. People living with or at risk of HIV experience stigma & discrimination and the wrong language perpetuates this.

===2020: [https://filtermag.org/language-addiction-treatment/ The Real Harms of Abusive, Stigmatizing Language in Addiction Treatment]===
*One study found that the terms “addict” and “substance abuser” led people to hold distinctly negative associations about the people they described. Another found that replacing less obviously pernicious terms, like “relapse” and “medication-assisted treatment,” with “recurrence of use” and “pharmacotherapy,” resulted in more positive views of people with substance use disorders.

===2017: [https://academic.oup.com/sleep/article/40/4/zsx039/3062257 People-Centered Language Recommendations for Sleep Research Communication]===
*While centering research design around what matters most to people with sleep disorders is critical, research communication must be similarly people-centered. One approach is using “people-centered language” in both professional and public communications. People-centered language is rooted in sociolinguistic research demonstrating that language both reflects and shapes attitudes. People-centered language puts people first, is precise and neutral, and respects autonomy.
*Sleep researchers may worry that adopting people-centered language will be onerous or hinder the use of elegant shorthand. However, convenience should not take priority over reducing stigma and better engaging the people this research is intended to serve.

===2017: [https://www.npr.org/sections/health-shots/2017/06/11/531931490/change-from-addict-to-person-with-an-addiction-is-long-overdue Why We Should Say Someone Is A 'Person With An Addiction,' Not An Addict]===
*"The new edition of its widely used AP Stylebook declares that "addict" should no longer be used as a noun. "Instead," it says, "choose phrasing like he was addicted, people with heroin addiction or he used drugs." In short, separate the person from the disease."
*"The new language has been widely welcomed. "It's very good — really well done," says John Kelly, an associate professor of psychiatry at Harvard and founder and director of the Recovery Research Institute at the Massachusetts General Hospital. Kelly was the lead author of a study published in 2010 that showed that clinicians — from the least educated up through doctoral-level professionals — take a more punitive stance when patients are described as "substance abusers" rather than "people with substance use disorder."
**Originally published on [https://undark.org/2017/06/06/associated-press-stylebook-addiction/ Undark]

===[https://www.shatterproof.org/sites/default/files/2021-02/Stigma-AddictionLanguageGuide-v3.pdf Shatterproof - Addiction Language Guide]===
*"These labels erased my humanity. Total strangers felt allowed to criticize or judge me, saying that I was ‘such a waste of life,’ ‘useless,’ or ‘just a drunk or addict.’ These words also carried the connotation that I was lazy, selfish, or a criminal. After a while, I began to believe these words, concluding that I no longer served a purpose, had opportunities, or deserved hope."

===[https://www.shatterproof.org/our-work/ending-addiction-stigma/understanding-addiction-stigma Shatterproof - 4 types of stigma]===
*There are several kinds of stigma that cause negative attitudes, stereotypes, shame, and fear toward people with addiction.

===[https://cmjcenter.org/wp-content/uploads/2017/07/CNUS-AppropriateLanguage.pdf The Center for NuLeadership on Urban Solutions]===
*When we are not called mad dogs, animals, predators, offenders and other derogatory terms, we are referred to as inmates, convicts, prisoners and felons — all terms devoid of humanness which identify us as “things” rather than as people.
*In an effort to assist our transition from prison to our communities as responsible citizens and to create a more positive human image of ourselves, we are asking everyone to stop using these negative terms and to simply refer to us as '''PEOPLE'''. '''People''' currently or formerly incarcerated, '''PEOPLE''' on parole, '''PEOPLE''' recently released from prison, '''PEOPLE''' in prison, '''PEOPLE''' with criminal convictions, but '''PEOPLE'''.

===[https://drive.google.com/drive/folders/1UNRXrgEUrxu60onoVL1l8d6HGo20AQXA Language Resources - Justice System]===
*Links to several documents

===[https://www.obesityaction.org/action-through-advocacy/weight-bias/people-first-language/ Weight Bias People-First Language]===
*The OAC has identified many areas where weight bias penetrates today’s society, such as media, entertainment, healthcare, employment, education and more. However, one of the most prevalent areas that the OAC is now tackling to eradicate weight bias and stigma is language. The OAC, along with other obesity-focused organizations in the community, are raising awareness of a new initiative titled People-First Language.

===[https://harmreduction.org/issues/harm-reduction-basics/undoing-stigma-facts/ RESPECT TO CONNECT: UNDOING STIGMA]===
*What Does Stigma Look Like?
**Stigma limits a person’s ability to access services they need because they feel unworthy of receiving or requesting services.
**Stigma creates barriers while receiving services by people feeling unwelcome or judged by program staff that offers services.

===[https://abovethelaw.com/2022/01/stigmatizing-stigmas/ Stigmatizing Stigmas]===
*"The foundation of most societal issues is rooted in hierarchies and ideologies. These two concepts are bound together by one term: stigma. Stigmas support hierarchies and give power to ideologies. Each level of any hierarchy is bound to be linked to a stigma, whether the stigma is about the people, their attitudes, mannerisms, professions, or other factors. Though often compared to their cousin, the stereotype, stigmas have much darker undertones."

===[https://www.aha.org/people-matter-words-matter The American Hospital Association (AHA)]===
*Using people-first language - Language matters in compassionate care, especially in behavioral health care, and that doesn’t mean just what you say in front of a patient. What you say behind closed doors with coworkers can be the seed for stigma and perpetuate discrimination against a person based on a physical or mental disorder. Using people-first language means speaking in a way that primarily acknowledges the person, rather than the illness or disability. Thanks to Linden Oaks Behavioral Health for being a source of this poster.

=='''Social Media'''==

===2022: [https://twitter.com/drannamvaldez/status/1591201711204765698 Dr. Anna Maria Valdez]===
*Twitter thread about hurtful ways to deal with someone trying to educate others about stigmatizing language and best practices for when being made aware of such language.

=='''Opposing Views - Smoker or Person-First'''==

===2023: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntad047/7086062?redirectedFrom=fulltext Embrace the Smoker: Person-First Language Is not a Solution to Stigma]===
*[https://twitter.com/MichaelChaiton/status/1640749889486311424 Twitter thread]
*Response: [https://academic.oup.com/ntr/article-abstract/25/8/1511/7152888?redirectedFrom=fulltext Overlooked Inequities in Language May Undermine Progress in Tobacco Control: Further Thoughts on the Need for Reflection]
*Original: [https://academic.oup.com/ntr/article/24/12/1847/6710205 Time to Stop Using the Word “Smoker”: Reflecting on the Role of Language in Advancing the Field of Nicotine and Tobacco Research]

===2021: [https://www.thinkinclusive.us/post/why-person-first-language-doesnt-always-put-the-person-first Why Person-First Language Doesn’t Always Put the Person First]===
*"Ultimately, the key is to ask, whenever possible, how a person chooses to identify, rather than making assumptions or imposing your own beliefs. Each person’s relationship to language and identity are deeply personal, and everyone’s identity choices are worthy of respect. I, who proudly chooses identity-first language and identifies as a disabled woman, am worthy of respect. Being who you choose to be – who you are – is something no language rule should ever take away."

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545113/ Editorial Perspective: The use of person-first language in scholarly writing may accentuate stigma]===

=='''Roadblocks and Barriers to Using Person-First Language'''==

===2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371927/ Person-first language: are we practicing what we preach?]===

=Suggestions to add to this page=

===2025: [https://www.linkedin.com/pulse/nonprofit-jargon-divides-here-words-use-jzsve/ Nonprofit Jargon Divides. Here Are Words to Use Instead.]===

===2025: [https://conscienhealth.org/2026/01/05/making-a-choice-perpetuate-or-challenge-obesity-stigma/ Making a Choice: Perpetuate or Challenge Obesity Stigma]===

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC8992888/ Avoiding Ableist Language: Suggestions for Autism Researchers]===

===1987: [https://sci-hub.wf/10.1086/228672 The Social Rejection of Former Mental Patients: Understanding Why Labels Matter]===

===[https://journals.lww.com/hep/pages/articleviewer.aspx?year=9900&issue=00000&article=00581&type=Fulltext Ending stigmatizing language in alcohol and liver disease: A liver societies’ statement†]===

===[https://pubs.asahq.org/monitor/article/87/7/e1/138350/Person-First-Language-in-Anesthesiology-Care Person-First Language in Anesthesiology Care]===

===[https://www.nih.gov/nih-style-guide/person-first-destigmatizing-language Person-first and Destigmatizing Language]===

===[https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addiction Words Matter - Terms to Use and Avoid When Talking About Addiction]===

===[https://www.ama-assn.org/system/files/ama-aamc-equity-guide.pdf American Medical Association and the Association of American Medical Colleges (AAMC) Center for Health Justice]===
*“Advancing Health Equity: A Guide to Language, Narrative and Concepts (including person-first language)

===[https://journals.lww.com/janac/abstract/2022/10000/the_intersectionality_of_hiv_related_stigma_and.4.aspx JANAC]===
*[https://edmgr.ovid.com/janac/accounts/ifauth.htm#Bias_Free_Language Bias-free language]

===[https://www.nih.gov/nih-style-guide/person-first-destigmatizing-language NIH Style Guide]===

=== 2024: [https://www.biomedcentral.com/epdf/10.1186/s12954-024-00951-w?sharing_token=iksdbJmNbsU0FCuLKTmOqW_BpE1tBhCbnbw3BuzI2RPfoghhpaw1aXYiTmPkOUEsYD7zfW3Oxi8XXRKS3L0aH_O8eh3cyggC1VGtf5w_6JyeTOXweo5IMQG1Q6z_QN5P8n2nBrlzQiNW05fih5qb9c8XPyeef-ba33MTIQ9eqe4%3D Challenges in legitimizing further measures against smoking in jurisdictions with robust infrastructure for tobacco control: how far can the authorities allow themselves to go?] ===

* Central to our discussion is the research literature concerned with the concept of state-paternalism in tobacco control—the line between an ethically justified interference with the freedom of those who smoke and an exaggerated infringement disproportionate to the same people’s right to live as they choose.
* In countries with an already advanced infrastructure for tobacco control, this dilemma might become quite intrusive for regulators. We ask that if people, who smoke are aware of and have accepted the risks, are willing to pay the price, smoke exclusively in designated areas, and make decisions uninfluenced by persuasive messages from manufacturers—is a further tightening of anti-smoking measures still legitimate?
** Conclusion: We recommend that a further intensification of smoking control in countries that already have a well-developed policy in this area requires that regulators start to exploit the opportunity that lies in the ongoing diversification of the recreational nicotine market.
* Karl Erik Lund and Gunnar Saebo; Harm Reduction Journal (2024) 21:33https://doi.org/10.1186/s12954-024-00951-w
* Funding: Norwegian Institute of Public Health (Governmental)

===2021: [https://derma.jmir.org/2021/1/e28415 The Use of Person-Centered Language in Medical Research Journals Focusing on Psoriasis: Cross-sectional Analysis]===

===[https://www.nih.gov/about-nih/what-we-do/science-health-public-trust/perspectives/writing-respectfully-person-first-identity-first-language Writing Respectfully: Person-First and Identity-First Language]===

===2023: [https://academic.oup.com/cid/article/76/10/1860/7016316 Call to Action: Prioritizing the Use of Inclusive, Nonstigmatizing Language in Scientific Communications]===

===2023: [https://www.psychiatrist.com/pcc/addiction/substance-use-disorders/curbing-physician-stigma-toward-adolescents-with-nicotine-opiate-use/ Curbing Physician Stigma Toward Adolescents With Nicotine and Opiate Use]===

===2023: [https://onlinelibrary.wiley.com/doi/full/10.1111/dar.13660#dar13660-bib-0068 Why stigma matters in addressing alcohol harm]===

===2023: [https://academic.oup.com/phe/advance-article/doi/10.1093/phe/phad003/7084788?ut&login=false#399497368 A Taxonomy of Non-honesty in Public Health Communication]===

===2022: [https://vimeo.com/showcase/9893575/video/779678704 Clive Bates at E-Cig Summit 2022]===
*Ontology - Stigmatizing labels. The difference between addiction and dependence.

===2014: [https://www.amjmed.com/article/S0002-9343(14)00770-0/fulltext Stop Talking ‘Dirty’: Clinicians, Language, and Quality of Care for the Leading Cause of Preventable Death in the United States]===

===2008: [https://pubmed.ncbi.nlm.nih.gov/18502551/ Stigma and the ethics of public health: not can we but should we]===

===2018: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6330014/ Substance use, recovery, and linguistics: The impact of word choice on explicit and implicit bias]===
*See also: [https://www.recoveryanswers.org/research-post/the-real-stigma-of-substance-use-disorders/ The real stigma of substance use disorders]

===2020: [https://filtermag.org/language-addiction-treatment/ The Real Harms of Abusive, Stigmatizing Language in Addiction Treatment]===

Nicotine - Stigma

2026-04-06T09:13:33Z

Skip: /* 2008: Stigma and the ethics of public health: not can we but should we */

Nicotine therapeutic benefits

2026-04-04T16:11:10Z

Skip: /* More Information */

<big>'''''Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that fewer people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine. Some of these studies show a potential benefit, not proof of a benefit. Some of the studies are animal studies, not human studies.'''''</big>
 
 
[[File:Nic Ther Ben.png|alt=Nicotine Therapeutic benefits banner|center]]
 

 

<big>'''Note: Some topics are subgroups under the main topic of "Mental Health." '''</big>
 

='''Acne'''=

===2010 [https://ijphjournal.it/article/view/5708 Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies]===
*Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis.
*Our meta-analysis underlines that there is no evidence to support an association between smoking habits and acne, although in three of the good quality papers a significant protection in the current smoker was found. It necessary to be cautious in declaring that smoking may provide a protective effect in the pathogenesis of acne because the analysis was based on only a small number of studies.

===2006 [https://www.sciencedirect.com/science/article/pii/S0022202X15330153 Severe Acne Vulgaris and Tobacco Smoking in Young Men]===
*It is crucial to emphasize that any positive effects found must be traced to specific tobacco components that can be therapeutically used without smoking (e.g., nicotine patches or gums), to avoid any “legitimatizing” of smoking based on its beneficial effects on health.
*Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P=0.0078).
*Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

===1993 [https://academic.oup.com/ced/article-abstract/18/2/100/6629365 Does smoking influence acne?]===
*[https://sci-hub.se/10.1111/j.1365-2230.1993.tb00986.x PDF of full study]
*The findings of this study support the hypothesis that some component of cigarette smoke, possibly nicotine, has an anti‐inflammatory action on acne.
 

='''ADD / ADHD / Attention / Cognition'''=

=== 2025 '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf060/8078909 Nicotine improves working memory via augmenting BDNF levels through α7 nAChR: evidence from clinical and pre-clinical studies]''' ===

* While smoking has been associated with many negative consequences to human health, one possible benefit is that nicotine could improve cognitive functions. Previous studies have suggested that smoking may influence brain-derived neurotrophic factor (BDNF) levels.
* Our research revealed that tobacco product use led to an increase in working memory and human plasma BDNF levels. Furthermore, nicotine was responsible for the elevation in BDNF levels, which showed dose-dependent increases in both serum and the hippocampus, and improved memory performance.
* Animal study (rat)
* ''Yingyan Li, PhD, Xin Li, Yaning Fu, PhD, Wenjun Mou, Zuxin Chen, PhD, Ping Wu, PhD, Fanglin Liu, PhD, Huan Chen, PhD, Hongwei Hou, PhD, Qingyuan Hu, PhD: Nicotine & Tobacco Research'', ntaf060, <nowiki>https://doi.org/10.1093/ntr/ntaf060</nowiki>

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.845646/full Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms]===
*"Our review of evidence supports the finding that individuals with ADHD are at greater vulnerability for both initiation and continuation of smoking (both cigarettes, e-cigarettes)."
*"Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes."
*Taylor, M. R., Carrasco, K., Carrasco, A., & Basu, A. (2022). Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms. Frontiers in Neuroscience, 16, 845646. https://doi.org/10.3389/fnins.2022.845646
*Funds for open access publication fees are contributed by the Faculty of Health, University of Canterbury and University of Canterbury library.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*High rates of smoking are observed among individuals with psychiatric disorders including schizophrenia, bipolar disorder, major depression, attention deficit hyperactivity disorder (ADHD) and comorbid substance use disorders (SUD). Because these psychiatric disorders are associated with various cognitive impairments, including deficits in attention, working memory, and response inhibition functions, the cognitive enhancing effects of nicotine may be especially important determinants of the initation and maintenance of smoking in this comorbid population. Growing evidence suggest that cognitive enhancing effects of nicotine may also contribute to the difficulty in quitting smoking, especially in individuals with psychiatric disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.tandfonline.com/doi/full/10.1080/10826084.2017.1334066 Causal Factors of Increased Smoking in ADHD: A Systematic Review]===
*One of the most striking comorbidities of ADHD is nicotine dependence. Youth diagnosed with ADHD are 2–3 times more likely to smoke than their peers without ADHD, initiate smoking earlier in life and progress more quickly and more frequently to regular use and dependence. Possible explanations for these increased risks are: (a) self-medication of ADHD symptoms with the stimulant nicotine; (b) ADHD symptoms like inattention and hyperactivity/impulsivity predispose for smoking initiation and impede smoking cessation; (c) peer pressure; and/or (d) common genetic or environmental determinants for ADHD and smoking.
*In contrast, the positive relation between ADHD and nicotine dependence is currently best explained by the self-medication hypothesis. This hypothesis has a clear pharmacological rationale and is supported by ample evidence, but awaits confirmation from longitudinal naturalistic studies.
*Citation: Jan van Amsterdam, Bauke van der Velde, Mieke Schulte & Wim van den Brink (2018) Causal Factors of Increased Smoking in ADHD: A Systematic Review, Substance Use & Misuse, 53:3, 432-445, DOI: 10.1080/10826084.2017.1334066

===2014: [https://www.medscape.com/viewarticle/827544_1 Adult Attention-Deficit/Hyperactivity Disorder and Nicotine Use: A Qualitative Study of Patient Perceptions]===
*Participants had different views about the link between cigarette smoking and ADHD. While the majority thought of nicotine as a sort of therapy, viewing smoking as a way to self-medicate symptoms of ADHD, motivations for nicotine use were also related to self-image, desire to belong to a peer-group, and a drive to undermine perceived social norms. Ultimately, these findings can be used by clinicians to improve treatment alliance and collaboration.
*[https://sci-hub.se/10.1186/1471-244x-14-141 Alternative Link]
*Citation: Liebrenz, M., Frei, A., Fisher, C. E., Gamma, A., Buadze, A., & Eich, D. (2014). Adult attention-deficit/hyperactivity disorder and nicotine use: a qualitative study of patient perceptions. BMC Psychiatry, 14(1). doi:10.1186/1471-244x-14-141

===2011 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353150/ Cognitive enhancers for the treatment of ADHD]===
*Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting approximately 8–9% of school-aged children and 4–5% of adults (Froehlich et al., 2007; Kessler et al., 2006; Visser et al., 2007). Although formally the disorder is characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity (APA, 2000), myriad phenotypic features—many of which are related to cognition broadly defined—have been shown to distinguish those with ADHD from those without the disorder.
*Together, these findings have led to the hypothesis that individuals with ADHD may smoke in order to alleviate requisite symptoms of the disorder and further suggest nicotine and/or nicotinic agonists can be used to improve aspects of cognitive function in these patients (McClernon and Kollins, 2008). Some support for this hypothesis has been provided by studies which have shown positive effects of nicotine on ADHD symptoms (Gehricke et al., 2009; Shytle et al., 2002) and cognitive performance (Levin et al., 1996; Potter and Newhouse, 2004) in non-smokers with ADHD. Whereas there are currently no FDA-approved nicotinic agonists to treat ADHD, laboratory and small-scale clinical trials have been conducted in recent years, and novel nicotinic pharmacotherapies are on the horizon.
*Citation: Bidwell LC, McClernon FJ, Kollins SH. Cognitive enhancers for the treatment of ADHD. Pharmacol Biochem Behav. 2011 Aug;99(2):262-74. doi: 10.1016/j.pbb.2011.05.002. Epub 2011 May 10. PMID: 21596055; PMCID: PMC3353150.

===2009 [https://pubmed.ncbi.nlm.nih.gov/20025370/ Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder]===
*Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.
*Citation: Gehricke, J. G., Hong, N., Whalen, C. K., Steinhoff, K., & Wigal, T. L. (2009). Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors, 23(4), 644–655. https://doi.org/10.1037/a0017441

===2009 [https://www.tandfonline.com/doi/abs/10.3109/15622970209150616 A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder]===
*All 10 subjects enrolled (six males, four females; mean age = 10 years, SEM = 0.8) completed the study. As assessed by the 48-item Conners Parent Rating Scale at endpoint and during the trial, there was a significantly greater reduction in ADHD symptoms on “Learning Problems” and “Hyperactivity” subfactors. Nausea, stomach ache, itching under patch and dizziness were the most frequently reported adverse effects associated with transdermal nicotine.
*Citation: R. Douglas Shytle, Archie A. Silver, Berney J. Wilkinson & Paul R. Sanberg (2002) A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder, The World Journal of Biological Psychiatry, 3:3, 150-155, DOI: 10.3109/15622970209150616

===2008 [https://www.sciencedirect.com/science/article/abs/pii/S0091305707003048?via%3Dihub Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to [[Special:MyLanguage/Abbreviations|'''ADHD''']].
*[https://sci-hub.st/https://doi.org/10.1016/j.pbb.2007.09.014 PDF Version]
*Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.
*Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.

===2008 [https://pmc.ncbi.nlm.nih.gov/articles/PMC2446482/ Transdermal Nicotine in Adult ADHD With Depression and Anxiety]===
*"This case report neither rules out the placebo effect, nor does it prove that transdermal nicotine is useful in managing adult ADHD with depression and anxiety. However, it does suggest that the beneficial effect of transdermal nicotine may be attributed to biobehavioral pathways common to chronic nicotine withdrawal and ADHD with depression and anxiety. Nicotine agonists and delivery systems may be new treatments for adult ADHD. Larger well-designed studies are warranted to evaluate the therapeutic potential of nicotine delivery systems in otherwise medically stable adults with ADHD accompanied by depression and anxiety. Further exploration of the nicotinic-cholinergic system may also expand our understanding of the neuropsychiatry underlying ADHD."
*Citation: Cocores JA. Transdermal nicotine in adult ADHD with depression and anxiety. Prim Care Companion J Clin Psychiatry. 2008;10(3):253-4. doi: 10.4088/pcc.v10n0312f. PMID: 18615164; PMCID: PMC2446482.
*Dr. Cocores reports no financial affiliations or other relationships relevant to the subject of this letter.

===2007 [https://www.academia.edu/2412620/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
*The data from diverse studies are generally consistent with the self-medication hypothesis and suggest that individuals with ADHD may smoke to alleviate symptoms associated with attention deficit, impulsivity, and hyperactivity. More studies on larger samples are necessary to assess the differential risks for adolescent smoking initiation that are associated with ADHD subtypes and with ODD and CD comorbidities.
*Citation: Gehricke, J.-G., Loughlin, S., Whalen, C., Potkin, S., Fallon, J., Jamner, L., … Leslie, F. (2007). Smoking to self-medicate attentional and emotional dysfunctions. Nicotine Tobacco Research, 9, 523–536. https://doi.org/10.1080/14622200701685039

===2007: [https://pubmed.ncbi.nlm.nih.gov/18022679/ Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.
**Citation: Potter AS, Newhouse PA. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav. 2008 Feb;88(4):407-17. doi: 10.1016/j.pbb.2007.09.014. Epub 2007 Sep 26. PMID: 18022679.
***Acknowledgement: Paywalled, unable to access.

===2006 [https://www.academia.edu/17983526/The_reinforcing_effects_of_nicotine_and_stimulant_medication_in_the_everyday_lives_of_adult_smokers_with_ADHD_A_preliminary_examination The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination]===
*The findings suggest that smokers with ADHD experience nicotine-related reductions in ADHD symptoms during their everyday lives.
*Citation: Gehricke, J. G., Whalen, C., Jamner, L., Wigal, T., & Steinhoff, K. (2006). The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination. Nicotine Tobacco Research, 8(1), 37–47. https://doi.org/10.1080/14622200500431619

===2006 [https://www.sciencedirect.com/science/article/abs/pii/S0031938405005627?via%3Dihub Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits]===
*The results showed nicotine-induced improvement on some measures of sustained attention in the low attention group and some decrement in working memory in the high attention group, which suggests that nicotine tends to optimize rather than improve performance on cognitive tasks.
*[https://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]
*Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2003: [https://www.academia.edu/2412608/Is_There_a_Link_Between_Adolescent_Cigarette_Smoking_and_Pharmacotherapy_for_ADHD Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?]===
*Self-report surveys, electronic diaries, and salivary cotinine all indicated that adolescents treated with pharmacotherapy for ADHD smoked less than their untreated counterparts over 2 years of high school. These convergent findings from 3 disparate indicators lend support to the self-medication hypothesis over the gateway hypothesis, although alternative explanations need further study. The findings also suggest that early treatment of psychological and behavioral problems may prevent or delay smoking initiation
*Citation: Whalen, C. K., Jamner, L. D., Henker, B., Gehricke, J.-G., & King, P. S. (2003). Is There a Link Between Adolescent Cigarette Smoking and Pharmacotherapy for ADHD? Psychology of Addictive Behaviors, 17(4), 332–335. https://doi.org/10.1037/0893-164X.17.4.332

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===2001 [https://psycnet.apa.org/record/2001-14365-012 Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder.]===
*This small study (40 participants) provided evidence that nicotine treatment can reduce severity of attentional deficit symptoms and produce improvement on an objective computerized attention task.
*Citation: Levin, E. D., Conners, C. K., Silva, D., Canu, W., & March, J. (2001). Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Experimental and Clinical Psychopharmacology, 9(1), 83–90. https://doi.org/10.1037/1064-1297.9.1.83

===1998 [https://pubmed.ncbi.nlm.nih.gov/9860103/ Transdermal nicotine effects on attention]===
*This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult non-smokers.
*[https://sci-hub.st/10.1007/s002130050750 PDF Version]
*Citation: Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J, Rose JE. Transdermal nicotine effects on attention. Psychopharmacology (Berl). 1998 Nov;140(2):135-41. doi: 10.1007/s002130050750. PMID: 9860103
*Acknowledgement: The authors thank R.J. Reynolds for financial support of the project. Work on this article was partially supported by Career Science Award (K05MH0122903) to Dr. Conners and Research Scientist Development Award (K02MH0098102) to Dr. March

===1996 [https://pubmed.ncbi.nlm.nih.gov/8741955/ Nicotine effects on adults with attention-deficit/hyperactivity disorder]===
*Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clinical trials with ADHD.
*[https://sci-hub.st/10.1007/BF02246281 PDF Version]
*Citation: Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl). 1996 Jan;123(1):55-63. doi: 10.1007/BF02246281. PMID: 8741955.
*Acknowledgement: The authors thank Dr. Allen Frances, Chairman of the Department of Psychiatry, Duke University Meidcal Center for his finanical support of the project. Work on this article was partially supported by Career Science Award (K05MH01229-03) to Dr. Conners and Research Scientist Development Award (K20MH00981-02) to Dr. March and a Young Investigator Award from the National Alliance for Research Schizophenia and Depression to Dr. Levin.

===1996: [https://pubmed.ncbi.nlm.nih.gov/8927677/ Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD)]===
*The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.
*Citation: Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull. 1996;32(1):67-73. PMID: 8927677.

===Year Unknown: Article: [https://www.adxs.org/en/page/192/nicotine-as-a-medication-for-adhd Nicotine as a medication for ADHD]===
*Lists references

 

='''Aging'''=

===2023: [https://www.nature.com/articles/s41467-023-36543-8 Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity]===
*Abstract "Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms."
**Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8
***Acknowledgement: This work was supported by grants from Shenzhen Science and Technology Program (KQTD20210811090117032), Shenzhen Key Laboratory of Viral Vectors for Biomedicine (ZDSYS20200811142401005), CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024) and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).

='''Akathisia'''=

===1997: [https://pubmed.ncbi.nlm.nih.gov/9399378/ Treatment of neuroleptic-induced akathisia with nicotine patches]===
*We administered 14 mg nicotine patches to 16 patients, all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia.
*[https://sci-hub.se/10.1007/s002130050436 PDF Version]
**Citation: Anfang MK, Pope HG Jr. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl). 1997 Nov;134(2):153-6. doi: 10.1007/s002130050436. PMID: 9399378.
 

='''Alcohol Use Disorder'''=

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

='''Allergies / Hayfever / Histamines''' (See also: Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis)=

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203434/ Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation]===
*Animal Study
*In this study, the effect of environmental tobacco smoke (ETS) on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated.
*In summary, ETS suppressed allergen-induced nasal responses including NHR by inhibiting allergen-specific Th2 cell responses. Although our present findings do not deny harmful effects of cigarette smoking, nicotine as a component of ETS may be a target to treat Th2-mediated allergic diseases, including allergic rhinitis (AR).
**Citation: Nishimura T, Kaminuma O, Saeki M, Kitamura N, Mori A, Hiroi T. Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation. Asia Pac Allergy. 2020 Apr 27;10(2):e18. doi: 10.5415/apallergy.2020.10.e18. PMID: 32411583; PMCID: PMC7203434.
***Acknowledgement: This work was supported in part by funding from the Smoking Research Foundation provided to Osamu Kaminuma.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440386/ Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium]===
*Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
**Citation: Skaaby T, Taylor AE, Jacobsen RK, et al. Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Sci Rep. 2017 May 22;7(1):2224. doi: 10.1038/s41598-017-01977-w. PMID: 28533558; PMCID: PMC5440386.
***Acknowledgement: This work was supported by the Medical Research Council (grant numbers: MR/J01351X/1, MC_UU_12013/6). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

===2014: [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085888 Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model]===
*Animal study
*In this study, nicotine treatment significantly ameliorated FA [Food Allergy], mainly due to the suppression of upregulated mucosal immune responses via α7 nAChRs on immune cells. Therefore, the therapeutic effects of nicotine and GTS-21 on the FA model raise the possibility that a strategy for drug discovery against FA by targeting α7 nAChRs could potentially have therapeutic benefits.
**Citation: Yamamoto T, Kodama T, Lee J, Utsunomiya N, Hayashi S, Sakamoto H, Kuramoto H, Kadowaki M. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS One. 2014 Jan 16;9(1):e85888. doi: 10.1371/journal.pone.0085888. PMID: 24454942; PMCID: PMC3894205.

===2008: [https://journals.aai.org/jimmunol/article/180/11/7655/84640/Nicotine-Primarily-Suppresses-Lung-Th2-but-Not Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens]===
*Animal Study
*hese results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia, mucous production, and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
**Citation: Neerad C. Mishra, Jules Rir-sima-ah, Raymond J. Langley, Shashi P. Singh, Juan C. Peña-Philippides, Takeshi Koga, Seddigheh Razani-Boroujerdi, Julie Hutt, Matthew Campen, K. Chul Kim, Yohannes Tesfaigzi, Mohan L. Sopori; Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens1. J Immunol 1 June 2008; 180 (11): 7655–7663. https://doi.org/10.4049/jimmunol.180.11.7655
***Acknowledgement: This work was supported in part by grants from the National Institutes of Health (R01-DA017003, R01-DA04208-15, and R01-DA042087S).

===2004: [https://link.springer.com/article/10.1007/s00011-004-1249-1 The effect of nicotine on basophil histamine release]===
*This study has demonstrated that nicotine agonists inhibit histamine release from human basophils.
*[https://sci-hub.st/10.1007/s00011-004-1249-1 PDF Full Version]
**Citation: Thompson-Cree, M.E.M., Stevenson, M.R., Shields, M.D. et al. The effect of nicotine on basophil histamine release. Inflamm. res. 53, 211–214 (2004). https://doi.org/10.1007/s00011-004-1249-1

='''Alzheimer / Dementia / Mild Cognitive Imparement (MCI)'''=
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

===2013 [https://link.springer.com/article/10.1007/s12017-013-8242-1 Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation]===
*Animal Study
*Taken together, these results demonstrate that nicotine prevents memory deficits and synaptic impairment induced by Aβ oligomers. In addition, nicotine improves memory in young APP/PS1 transgenic mice before extensive amyloid deposition and senile plaque development, and also in old mice where senile plaques have already formed.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/s12017-013-8242-1 PDF Version]
*Citation: Inestrosa, N.C., Godoy, J.A., Vargas, J.Y. et al. Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation. Neuromol Med 15, 549–569 (2013). doi: 10.1007/s12017-013-8242-1
*Acknowledgements: We thank Dr. Rodrigo Varas for his help with the electrophysiological studies of the α7-nAChR. This work was supported by a grant from FONDECYT No 120156 to N.C.I; predoctoral fellowships from CONICYT to G.G.F., M.S.A. F.G.S., J.A.R. and from Fundación Gran Mariscal de Ayacucho to J.Y.V. The Basal Center of Excellence in Science and Technology CARE was funded by CONICYT/PFB 12/2007.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/ Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment.
*Safety and tolerability for transdermal nicotine were excellent.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/pdf/znl91.pdf PDF Version]
*Citation: Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology. 2012 Jan 10;78(2):91-101. doi: 10.1212/WNL.0b013e31823efcbb. PMID: 22232050; PMCID: PMC3466669.

===2010 [https://www.tandfonline.com/doi/abs/10.1080/13607860220126808 Nicotine's effect on neural and cognitive functioning in an aging population]===
*Recent advances in nicotine research have pointed to a number of cognitive and neurological benefits that have been linked to the ingestion of nicotine.
*This article examines cognitive decline in the elderly and looks at nicotine's potential role in ameliorating this decline.
*Nicotine’s effects on cognitive functioning have shown it to increase perception, visual attention,and arousal as well as improving the speed and accuracy of motor functioning while decreasing reaction time and inhibiting declines in efficiency. In addition, research has shown nicotine to improve long-term and short-term memory, and to increase the ability to withhold inappropriate responses.
*Research has revealed that chronic exposure to nicotine produces an unusual up-regulation of the nicotinic receptor sites. This increase in receptor sites is thought to provide some protection against neuro-degenerative disorders such as Alzheimer’s disease.
*[https://sci-hub.st/10.1080/13607860220126808 PDF Version]
*Citation: K. N. Murray & N. Abeles (2002) Nicotine's effect on neural and cognitive functioning in an aging population, Aging & Mental Health, 6:2, 129-138, DOI: 10.1080/13607860220126808

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783.
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12436427/ Nicotinic receptors in aging and dementia]===
*Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects.
*Acute nicotine administration can improve performance of patients with AD on cognitive tasks, including verbal learning and memory, attention in a continuous performance task, and accuracy in a visual attention task.
*In addition to its ability to reverse cognitive deficits following aging, nicotine has been shown to protect against neurotoxic insult in vitro and in vivo. This suggests that nicotine has a dual effect on brain function following aging or injury, such that it can rescue function of remaining neurons, as well as saving neurons that might otherwise undergo cell death.
*[https://sci-hub.st/10.1002/neu.10102 PDF Version]
*Citation: Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. J Neurobiol. 2002 Dec;53(4):641-55. doi: 10.1002/neu.10102. PMID: 12436427.
*Keywords: nAChR; neuroprotection; Alzheimer’s disease; Parkinson’s disease; acetylcholine

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Alzheimer's disease (AD)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1410164/ Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease]===
*Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds).
*[https://sci-hub.st/10.1007/BF02247426 PDF Version]
*Citation: Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology (Berl). 1992;108(4):485-94. doi: 10.1007/BF02247426. PMID: 1410164.
*Acknowledgements. This research was supported by British-American Tobacco Co. Ltd. BJS thanks the Wellcome Trust and the Eleanor Peel Foundation for support.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in enhancement of performance, and protection against Alzheimer's disease (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1989 [https://pubmed.ncbi.nlm.nih.gov/2597885/ The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type]===
*Nicotine in patients with dementia of the Alzheimer type (DAT) produced a significant and marked improvement in discriminative sensitivity and reaction times on a computerised test of attention and information processing. Nicotine also improved the ability of DAT patients to detect a flickering light in a critical flicker fusion test. These results suggest that nicotine may be acting on cortical mechanisms involved in visual perception and attention, and support the hypothesis that acetylcholine transmission modulates vigilance and discrimination. Nicotine may therefore be of some value in treating deficits in attention and information processing in DAT patients.
*[https://sci-hub.st/10.1192/bjp.154.6.797 PDF Version]
*Citation: Sahakian B, Jones G, Levy R, Gray J, Warburton D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry. 1989 Jun;154:797-800. doi: 10.1192/bjp.154.6.797. PMID: 2597885.
 

='''Antimicrobial Agent'''=
*As a follow-up to these provocative findings, future related studies should examine whether nicotine exerts its anti-microbial effects against a much broader range of indigenous microflora than has been studied so far, along with focusing on the molecular biologic mechanisms and host pathologic changes associated with nicotine-mediated killing of the oral and intestinal microflora.
**Citation: Pavia CS, Plummer MM. Clinical implications of nicotine as an antimicrobial agent and immune modulator. Biomed Pharmacother. 2020 Sep;129:110404. doi: 10.1016/j.biopha.2020.110404. Epub 2020 Jun 27. PMID: 32603888; PMCID: PMC7320263.
***Acknowledgement: This work was partially supported by funds provided by the Department of Biomedical Sciences, NYIT College of Osteopathic Medicine. The authors thank the publisher of the Journal of Medical Microbiology (JMM) for granting us permission to reuse in this paper, without being subject to any copyright infringement, some of the material previously published by one of us (CSP) in the JMM. We also thank Jane Pavia for contributing to the design of the graphical abstract.
 

='''Aphthous ulcers''' (See also: Behcet's disease)=

===2015: [https://pmc.ncbi.nlm.nih.gov/articles/PMC4387635/ Use of pure nicotine for the treatment of aphthous ulcers]===
*The theory that nicotine is known as the protective factor is also supported by three case reports, in which aphthous ulcers were prevented or healed while the patients used nicotine replacement materials.
*To summarize, the use of pure nicotine in therapeutic forms, seems to be a proper alternative to treat aphthous ulcers; however, there has not been any evidence-based case-control study to prove such claim.
**Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

===2014: [https://pubmed.ncbi.nlm.nih.gov/25584320/ Recurrent aphthous ulcers among tobacco users- hospital based study]===
*The tobacco consumers have less frequency of aphthous ulceration compared non users.
**Citation: Mohamed S, Janakiram C. Recurrent aphthous ulcers among tobacco users- hospital based study. J Clin Diagn Res. 2014 Nov;8(11):ZC64-LC66. doi: 10.7860/JCDR/2014/10368.5145. Epub 2014 Nov 20. PMID: 25584320; PMCID: PMC4290331.

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2004: [https://pubmed.ncbi.nlm.nih.gov/15370162/ The relationship between smoking cessation and mouth ulcers]===
*Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.
**Citation: McRobbie H, Hajek P, Gillison F. The relationship between smoking cessation and mouth ulcers. Nicotine Tob Res. 2004 Aug;6(4):655-9. doi: 10.1080/14622200410001734012. PMID: 15370162.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===
*This study shows that a group of RAS patients is significantly less likely to contain smokers than a matched control population, and among smokers the level of cigarette use was significantly lower in RAS patients than the control population. The perceived negative association between RAS and smoking was supported by this epidemiological study.
*[https://sci-hub.st/10.1034/j.1601-0825.2002.01826.x PDF Version]
**Citation: Atkin PA, Xu X, Thornhill MH. Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Dis. 2002 May;8(3):173-6. doi: 10.1034/j.1601-0825.2002.01826.x. PMID: 12108762.

===2000: [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418

===1992: [https://pubmed.ncbi.nlm.nih.gov/1408021/ Smokeless tobacco use prevents aphthous stomatitis]===
*In (contrast to cigarette smoking, however, few components other than nicotine are systemically absorbed by ST users. Thus if the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.
*[https://sci-hub.se/10.1016/0030-4220(92)90296-3 PDF Version]
**Citation: Grady D, Ernster VL, Stillman L, Greenspan J. Smokeless tobacco use prevents aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):463-5. doi: 10.1016/0030-4220(92)90296-3. PMID: 1408021.

===1991 [https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1991.tb121180.x?sid=nlm%3Apubmed Recurrent aphthous ulcers and nicotine]===
*The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers.
*[https://sci-hub.st/10.5694/j.1326-5377.1991.tb121180.x PDF Version]
**Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x
 

='''Arthritis/Skeletal'''=

==Osteoarthritis==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2019 [https://journals.aai.org/jimmunol/article/203/2/485/107400/Nicotine-Attenuates-Osteoarthritis-Pain-and-Matrix Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor]===
*In conclusion, stimulation of α7-nAChRs by nicotine attenuates MIA-induced OA pain and cartilage degradation. This protective effect of nicotine can be associated with the inhibition of MMP-9 overexpression through the PI3K/Akt/NF-κB signaling pathway. Although the use of nicotine is limited by its nonspecific effects, this study provides novel evidence supporting the future development of therapeutic strategies for inflammatory diseases via the cholinergic anti-inflammatory pathway.
**Citation: Teng P, Liu Y, Dai Y, Zhang H, Liu WT, Hu J. Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor. J Immunol. 2019 Jul 15;203(2):485-492. doi: 10.4049/jimmunol.1801513. Epub 2019 May 31. PMID: 31152077.
***This work was supported by grants from the National Natural Science Foundation of China (81373397, 81672218, and 81603092) and the Department of Science, Education, and Health Program of Jiangsu Province (QNRC 2016606 and QNRC 2016604).

==Rheumatoid arthritis (collagen-induced arthritis CIA in mice)==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2016 [https://www.spandidos-publications.com/mmr/14/6/5057 Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration]===
*Animal study
*Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.
**Citation: Li S, Zhou B, Liu B, Zhou Y, Zhang H, Li T, Zuo X. Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration. Mol Med Rep. 2016 Dec;14(6):5057-5064. doi: 10.3892/mmr.2016.5904. Epub 2016 Oct 31. PMID: 27840928; PMCID: PMC5355730.
***Acknowledgement: The present study was supported by a grant from the National Natural Science Foundation of China (grant no. 81571602).

===2014 [https://pubmed.ncbi.nlm.nih.gov/24313917/ Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells]===
*Animal Study
*Nicotine stimulation attenuated signs and severity of arthritis in mice. Activation of nicotine acetylcholine receptors on in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may play a potential role in alleviating arthritis in mice.
*[https://sci-hub.st/10.3109/14397595.2013.862352 PDF Full paper]
**Citation: Yang Y, Yang Y, Yang J, Xie R, Ren Y, Fan H. Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells. Mod Rheumatol. 2014 Sep;24(5):781-7. doi: 10.3109/14397595.2013.862352. Epub 2013 Dec 9. PMID: 24313917.
***Acknowledgement: This work was supported by The Shanghai Committee of Science and Technology Project, China (Grant No. 12GWZX0201,11140902900).

===2014 [https://www.sciencedirect.com/science/article/abs/pii/S0014299914003033 Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine]===
*Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses, may improve the Th1/Th2 imbalance in CIA, and provide a new justification for its application in the clinical treatment of RA.
*[https://sci-hub.st/10.1016/j.ejphar.2014.04.019 PDF Full paper]
**Citation: Wu S, Luo H, Xiao X, Zhang H, Li T, Zuo X. Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol. 2014 Jul 15;735:97-104. doi: 10.1016/j.ejphar.2014.04.019. Epub 2014 Apr 19. PMID: 24755145.
***Acknowledgement: This work was supported by a grant from the National Natural Science Foundation of China, People's Republic of China [81102261] and the Innovative Research Funds for the Central South University, People's Republic of China. [CX2012B088].

===2009 [https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.24177 Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice]===
*Animal Study
*Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction.
**Citation: van Maanen MA, Lebre MC, van der Poll T, LaRosa GJ, Elbaum D, Vervoordeldonk MJ, Tak PP. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 2009 Jan;60(1):114-22. doi: 10.1002/art.24177. PMID: 19116908.

='''Ataxia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

= '''Auditory''' =

===2021 [https://www.nature.com/articles/s41598-021-92588-z Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers]===
*The present study evaluated acute effects of oral nicotine treatment on three auditory tasks in young adult and elderly, healthy, non-smoking individuals. All had normal hearing within the frequency range of the stimuli presented for the three tasks. Compared to pre-treatment performance, nicotine improved frequency discrimination. Compared to placebo, nicotine produced no overall effects on the two frequency related tasks, but significantly improved intensity discrimination, with more improvement obtained for those who had lower baseline performance. The present results support the hypothesis that nicotine enhances auditory processing, but this enhancement is task-dependent.
*[https://www.nature.com/articles/s41598-021-92588-z.pdf PDF Version]
*Citation: Sun, S., Kapolowicz, M.R., Richardson, M. et al. Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers. Sci Rep 11, 13187 (2021). doi: 10.1038/s41598-021-92588-z

===2019 [https://pubmed.ncbi.nlm.nih.gov/31832719/ Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers]===
*Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.
*[https://sci-hub.se/10.1007/s00213-019-05421-x PDF Version]
*Citation: Pham CQ, Kapolowicz MR, Metherate R, Zeng FG. Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers. Psychopharmacology (Berl). 2020 Mar;237(3):833-840. doi: 10.1007/s00213-019-05421-x. Epub 2019 Dec 12. PMID: 31832719; PMCID: PMC7039769.
*Acknowledgements: This research was supported by grants from the National Institutes of Health to FGZ (5R01DC015587), to RM (4R01-DC013200) and a pre-doctoral fellowship to CQP (UL1-TR000153).
*Keywords: Acetylcholinergic systems; Auditory processing; Nicotine; Selective attention; Spectral ripple discrimination; Temporal gap detection; Tone in noise detection.

='''Autism'''=

===2025: [https://link.springer.com/article/10.1007/s12035-025-04894-6 Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism]===
*Animal Study
*Accumulating evidence indicates that nicotinic receptor subtypes are altered in the brains of autistic individuals, and nicotinic acetylcholine receptors (nAChRs) play essential roles in autistic profiles in BTBR T+ Itpr3tf/J mice.
*Biochemical analysis showed that nicotine had significantly decreased the concentration of inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, and GM-CSF in the serum, and reduced the expression levels of intracellular pro-inflammatory cytokines (IL-17 & IFN-γ) on CD4+ and CD8+ T cells in the blood while mecamylamine reversed the effect of IL-17+ CD4+ T cells.
*Nicotine administration up-regulated the expressions of α7, α4, and β2 nAChRs in the prefrontal cortex in BTBR T+ Itpr3tf/J mice.
*The current results indicate that nAChRs play a significant role, at least in part, in ASD and might serve as a crucial target for therapeutic interventions in ASD.
**Citation: AlSharari, S.D., Mahmood, H.M., Alasmari, A.F. et al. Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism. Mol Neurobiol (2025). https://doi.org/10.1007/s12035-025-04894-6
***Acknowledgement: Researchers Supporting Project number (RSPD2025R829), King Saud University, Riyadh, Saudi Arabia. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

===2020: [https://pubmed.ncbi.nlm.nih.gov/32691528/ The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model]===
*Animal Study
*Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people.
*Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism.
*Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model.
*LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.
*[https://sci-hub.st/10.1002/aur.2342 PDF Full paper]
**Citation: Mahmood HM, Aldhalaan HM, Alshammari TK, Alqasem MA, Alshammari MA, Albekairi NA, AlSharari SD. The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model. Autism Res. 2020 Aug;13(8):1311-1334. doi: 10.1002/aur.2342. Epub 2020 Jul 21. PMID: 32691528.
***Acknowledgement: The authors would like to thank the support from the Center for Autism Research (CFAR), King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia.

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
**Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
***Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).

===2016: [https://pmc.ncbi.nlm.nih.gov/articles/PMC5101145/ Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia]===
*Animal Study
*
**Citation:
***Acknowledgement:

===2016: [https://pubmed.ncbi.nlm.nih.gov/27638450/ Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system]===
*Animal Study
*
*[https://sci-hub.st/10.1016/j.neuropharm.2016.09.013 PDF Full paper]
**Citation:
***Acknowledgement:

===2015: [https://pubmed.ncbi.nlm.nih.gov/26337613/ Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system]===
*Animal Study
*
**Citation:
***Acknowledgement:
 

='''Behcet's disease''' (See also: Aphthous ulcers)=
*Post on [https://healthunlocked.com/behcetsuk/posts/138632782/nicotine-and-it%E2%80%99s-effects-on-my-beh%C3%A7et%E2%80%99s-for-the-positive Behçet's UK]. A person started smoking seeking relief from the pain they suffered because of Behcet's disease.

===2010 [https://academic.oup.com/rheumatology/article/49/3/501/1786816 Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series]===
*In this report, we describe five ex-smoker [[Special:MyLanguage/Abbreviations|'''BD''']] patients with active mucocutaneous lesions, not responsive to standard pharmacological treatments and treated with transdermal nicotine patches. Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of all mucocutaneous lesions within 6 months of observation.
**Citation: Giovanni Ciancio, Matteo Colina, Renato La Corte, Andrea Lo Monaco, Francesco De Leonardis, Francesco Trotta, Marcello Govoni, Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series, Rheumatology, Volume 49, Issue 3, March 2010, Pages 501–504, doi: 10.1093/rheumatology/kep401

===2007 [https://www.jidonline.org/article/S0022-202X(15)33112-2/fulltext Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease]===
*"In conclusion, we observed substantial inhibitory effects of CSE and nicotine on IL-8 and to a lesser extent on IL-6 release by human keratinocytes and HMEC-1 endothelial cells. These findings may explain the beneficial effect of smoking in BD, also because IL-8, and to some extent IL-6, are likely to induce pivotal proinflammatory signals in this disease (Lee et al., 1993). Nicotine may cause immunoregulation by affecting chemokine/cytokine production. This study also demonstrates the different behavior of cells in terms of cytokine release when stimulated with BD patients' sera compared to those of healthy individuals. The in vitro evidence of beneficial effects of nicotine in BD is fundamental to our ongoing clinical trial with nicotine transdermal patches in BD. In addition, the detected beneficial effect of biochanin A implicates this compound as a candidate for future developments in aphthae treatment. The development of topical nicotinic cholinergic receptor subtype-specific agonists is likely to exhibit beneficial effects on skin and mucosae without inducing systemic adverse effects."
**Citation: Kalayciyan A, Orawa H, Fimmel S, Perschel FH, González JB, Fitzner RG, Orfanos CE, Zouboulis CC. Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease. J Invest Dermatol. 2007 Jan;127(1):81-9. doi: 10.1038/sj.jid.5700492. Epub 2006 Sep 28. PMID: 17008886.
***Acknowledgement: Dr Kalayciyan was supported by a grant of the Berlin Foundation for Dermatology. The research project was supported by the Deutsches Register Morbus Adamantiades–Behçet e.V.

===2000 [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418
 

='''Brain Injuries, Strokes, Brain Diseases'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/39921606/ The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]===
*Animal Study
*The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke. This finding suggests that targeting the BBB, especially endothelial cells, with nicotine treatment is a promising therapeutic strategy for brain injury after ischemic stroke.
**Citation: Pang Q, Yan X, Chen Z, Yun L, Qian J, Dong Z, Wang M, Deng W, Fu Y, Hai T, Chen Z, Rong X. The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier. Nicotine Tob Res. 2025 Feb 8:ntaf034. doi: 10.1093/ntr/ntaf034. Epub ahead of print. PMID: 39921606.
***Acknowledgement: Paywalled, unable to access

===2024: [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://pubmed.ncbi.nlm.nih.gov/38698493/ Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury]===
*Animal study
*Conclusioin: "Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions."
**Citation: Wang D, Li X, Li W, Duong T, Wang H, Kleschevnikova N, Patel HH, Breen E, Powell S, Wang S, Head BP. Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury. Br J Pharmacol. 2024 Sep;181(17):3082-3097. doi: 10.1111/bph.16395. Epub 2024 May 2. PMID: 38698493.
***Acknowledgement: H. H. P. and B. P. H. hold equity and are non-paid consultants with Eikonoklastes Therapeutics LLC. Funding information: (TRDRP 2020 T31IR1834 to BPH, VA Merit BX003671 and VA RCS BX006318 to BPH, AL210059 to BPH, Craig H. Neilsen Foundation 886964 to SW and BX005229 to HHP).

===2004: [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===
*Several studies have shown that nicotine treatment can attenuate cognitive deficits produced by medial septal lesions, lesions of the nucleus basalis, and traumatic brain injury.
*[https://sci-hub.st/10.1196/annals.1332.019 PDF Version]
**Citation: Pauly JR, Charriez CM, Guseva MV, Scheff SW. Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease. Ann N Y Acad Sci. 2004 Dec;1035:316-34. doi: 10.1196/annals.1332.019. PMID: 15681815.
***Acknowledgements: This work was supported by grants from the National Institutes of Health (NS42196 to J.R.P. and NS39828 to S.W.S.) and the Kentucky Tobacco Research and Development Center. We acknowledge the technical assistance of Melissa Yingling and Khaled Tanwir.

='''Cancer / Cancer Treatments'''=
===2021 [https://www.mdpi.com/1660-3397/19/2/118 α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells]===
*Animal Study
*We tested the effects of nicotine, which is an agonist for all nAChRs with the exception of α9 subtype for which it is antagonist. At concentrations of 0.001–0.1µL/mL (6.1 µM–0.61 mM), nicotine exerted no effect on the proliferative activity of glioma C6 cells and the loss of viability was 1–4% (Figure S2). Analysis by light microscopy showed that nicotine at concentrations of 1 µL/mL (6.1 mM) and higher induced morphological changes like cell rounding up and loss of processes followed by surface detachment (Figure 3). Despite these changes, we investigated the effect of nicotine at a concentration of 1 μL/mL (6.1 mM) on the proliferation and viability of C6 cells. At this nicotine concentration, inhibition of proliferation was observed, which after 72 h led to a decrease in the number of cells by more than two times; the viability was also reduced (Figure S2). However, it should be taken into account that the reason for such a strong decrease in the concentration of cells may be their detachment from the surface and, as a consequence, the cessation of division. We tested acetylcholine at concentrations ranging from 2 µM to 2 mM with incubation times of 24, 48 and 72 h. No effects of acetylcholine were observed.
**Citation: Terpinskaya, T. I., Osipov, A. V., Kryukova, E. V., Kudryavtsev, D. S., Kopylova, N. V., Yanchanka, T. L., Palukoshka, A. F., Gondarenko, E. A., Zhmak, M. N., Tsetlin, V. I., & Utkin, Y. N. (2021). α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Marine Drugs, 19(2), 118. https://doi.org/10.3390/md19020118
***Acknowledgement: This work was supported by the Belarusian Republican Foundation for Fundamental Research, project number M20R-254, and the Russian Foundation for Basic Research, project number 20-54-00033.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S001448272030416X?via%3Dihub Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells]===
*Nicotine inhibits ovarian cancer cell ERK and p38 [[Special:MyLanguage/Abbreviations|'''MAPK''']] signaling.
*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]
**Citation: Sarah J. Harmych, Jay Kumar, Mesa E. Bouni, Deborah N. Chadee, Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells, Experimental Cell Research, Volume 394, Issue 1, 2020, 112167, ISSN 0014-4827, doi: 10.1016/j.yexcr.2020.112167.
***Acknowledgements: This work was supported by the National Institutes of Health [R15 CA199164] and [R15 CA241898] to D.N.C.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

='''Cannabis / THC'''=
===2020 [https://pubmed.ncbi.nlm.nih.gov/32034447/ Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial]===
*The findings provide the first evidence that [[Special:MyLanguage/Abbreviations|NP (Nicotine Patch)]] may be able to attenuate NA (negative affect) - related withdrawal symptoms in individuals with cannabis use disorder who are not heavy users of tobacco or nicotine.
*[https://sci-hub.se/10.1007/s00213-020-05476-1 PDF Version]
*Citation: Gilbert DG, Rabinovich NE, McDaniel JT. Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial. Psychopharmacology (Berl). 2020 May;237(5):1507-1519. doi: 10.1007/s00213-020-05476-1. Epub 2020 Feb 7. PMID: 32034447.
*Acknowledgement: The study was supported by NIH grant R01DA031006 awarded to David Gilbert.
*Keywords: Cannabis; Marijuana; Negative affect; Nicotine; Smoking; THC; Testing effect; Withdrawal symptoms.

= '''Cardiovascular''' =
*See also: Brain Injuries and Strokes

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38529793/ Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects] ===
* This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers.
* PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
* Nicotine patches appear to promote blood vessel formation, without adverse effects.

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2015 [https://www.nature.com/articles/srep15895 Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3] ===

* The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis.
* The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group.
* The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
* Animal study (mice)
* Ge Li-Sha, Zhao Jing-Lin, Chen Guang-Yi, Liu Li, Zhou De-Pu & Li Yue-Chun ''Scientific Reports'' volume 5, Article number: 15895 (2015)

='''Chlamydia Pneumoniae'''=
*Chlamydia pneumoniae is a type of bacteria that can cause respiratory tract infections, such as pneumonia. C. pneumoniae is one cause of community-acquired pneumonia or lung infections developed outside of a healthcare setting. However, not everyone exposed to C. pneumoniae will develop pneumonia. [https://www.cdc.gov/pneumonia/atypical/cpneumoniae/index.html Source: US CDC]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''Cognitive / IQ / Memory'''=
*See also: Sleep - REM

=== 2024: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/ An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence] ===
*Conclusion: Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.
*Citation: Harry J. Green, Olivia K. O’Shea, Jack Cotter, Helen L. Philpott, and Nik Newland. Harm Reduct J. 2024; 21: 78. Published online 2024 Apr 6. doi: 10.1186/s12954-024-00993-0 PMCID: PMC10998423

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnins.2023.1252705/full Editorial: Nicotine and its derivatives in disorders of cognition: a challenging new topic of study] ===

* Front. Neurosci., 18 July 2023 Sec. Neurodegeneration Volume 17 - 2023 | <nowiki>https://doi.org/10.3389/fnins.2023.1252705</nowiki>
* Albert Gjedde, Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
* Nicotine is a compound of considerable interest to neuroscience, in contexts of physiology as well as pathology of brain functions related to neurotransmitter mechanisms. Nicotine is an alkaloid that exists naturally in plants such as tomatoes and potatoes, with the highest levels in the tobacco plant.
* In mammalian brains, nicotine has multiple actions that appear to be accidents of evolution, as no specific relation springs to mind between the functions of nicotine in plants and animals.
* The following discussion expands upon the three topics of biology, therapy, and possible prevention, as related to cognition, in the three reviews and the three original studies included in the collection.
** Conclusion: Questions remain of how nicotine treatment in normal aging should proceed, including length of treatment, dose of nicotine, handling of smokers, effects of AD risk factors, and many others. While data from studies of psychiatric and memory-impaired subjects indicate that nicotine may relieve cognitive symptoms, it is mandatory to test the benefits of nicotine in normal aging in order to fill gaps in the literature and to verify the extent to which nicotine is useful as a pharmacologic agent that prevents pathological aging.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36736944/ Nicotine's effect on cognition, a friend or foe?] ===
* In this review, we first introduce the beneficial effect of nicotine on cognition including attention, short-term memory and long-term memory. We next summarize the beneficial effect of nicotine on cognition under pathological conditions, including Alzheimer's disease, Parkinson's disease, Schizophrenia, Stress-induced Anxiety, Depression, and drug-induced memory impairment.
* We can only access the abstract, but would be interested to read the whole thing if anyone can help?
* Human study
* Qian Wang, Weihong Du, Hao Wang, Panpan Geng, Yanyun Sun, Junfang Zhang, Wei Wang, Xinchun Jin, PMID: 36736944 DOI: 10.1016/j.pnpbp.2023.110723

=== 2021: [https://www.spandidos-publications.com/10.3892/mmr.2021.12037# Molecular insights into the benefits of nicotine on memory and cognition] ===

* Published online on: March 25, 2021 Molecular Medicine Reports <nowiki>https://doi.org/10.3892/mmr.2021.12037</nowiki> Article Number: 398
* Author: Ahmad Alhowail

===2021: [https://www.sciencedirect.com/science/article/abs/pii/S1001841721007804 Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS]===
*Animal study
*Exposure to nicotine mainly altered the secretion of serotonin, kynurenic acid, choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition, and the change are closely related to the dose and duration of exposure.
**Citation: Chen Z, Fu L, Liu X-A, Yang Z, Li W, Li F, Luo Q. Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS. Chin Chem Lett. 2022;33(6):3101–5.
***Acknowledgement: This work was financially supported by the National Natural Science Foundation of China (No. 22076197), the Scientific Instrument Developing Project of the Chinese Academy of Sciences (No. YJKYYQ20200034), Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development (No. XMHT20190204002), Shenzhen Science and Technology Innovation Commission (No. JCYJ20200109115405930), Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020B1515120080).
*Article: [https://medicalxpress.com/news/2021-10-reveal-nicotine-hippocampal-dependent-cognition.html Researchers reveal how nicotine influences hippocampal-dependent cognition] "These results suggested the acute exposure to nicotine was beneficial to protect the neurons, especially cognitive enhancement, and the elevated picolinic acid continually protected neuronal cognitive function after nicotine withdrawal. Furthermore, the dynamic alterations of neurotransmitter metabolism induced by nicotine might be a possible protective mechanism of nicotine on hippocampal dependent cognition."

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0306452220304723?via%3Dihub Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study]===
*Nicotine improves sustained attention and reduces distractor interference, promoting cognitive stability. Nicotine enhances response times without differential impact on task switching or distraction.
*[https://sci-hub.se/10.1016/j.neuroscience.2020.07.029 PDF Version]
*Citation: Stefan Ahrens, Christiane M. Thiel, Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study, Neuroscience, Volume 444, 2020, Pages 43-53, ISSN 0306-4522, doi: 10.1016/j.neuroscience.2020.07.029.
*Acknowledgements: This work was supported by a grant from the German Research Foundation DFG TH766/8-1.
*Key words: nicotine, cholinergic, cognitive control, distraction, task switching, neuroimaging

===2019: [https://www.frontiersin.org/articles/10.3389/fnins.2018.01002/full#B5 Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review]===
*Nicotine lowers learning and memory impairment in some neurological disorders.
*Citation: Majdi, A., Kamari, F., & Gjedde, A. (2019). Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.01002

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.nature.com/articles/npp201715 Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention]===
*Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory–inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.
**Citation: Bueno-Junior, L., Simon, N., Wegener, M. et al. Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Neuropsychopharmacol 42, 1590–1598 (2017). https://doi.org/10.1038/npp.2017.15
***Acknowledgement: This work was supported by São Paulo Research Foundation, Brazil (FAPESP; fellowships 2012/21387-8 and 2012/06123-4) for investigator LSBJ, R01MH084906 (BM), and a pilot fund from the Center for Evaluation of Nicotine in Cigarettes (NWS). The authors declare no conflict of interest.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]

===2012: [https://pubmed.ncbi.nlm.nih.gov/22503574/ The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition]===
*The e-cigarette can reduce desire to smoke and nicotine withdrawal symptoms 20 minutes after use.
*The nicotine content in this respect may be more important for males.
*The first study to demonstrate that the nicotine e-cigarette can improve working memory.
*[https://sci-hub.se/10.1016/j.addbeh.2012.03.004 PDF Version]
*Citation: Dawkins, L., Turner, J., Hasna, S., & Soar, K. (2012). The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition. Addictive Behaviors, 37(8), 970–973. doi:10.1016/j.addbeh.2012.03.004
*Electronic Cigarette Company (TECC) supplied the e-cigarettes and cartridges for this study. TECC had no involvement in the design or conduct of the study.

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated

===2003 [https://www.nature.com/articles/1300202 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects]===
*Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention.
*[https://www.nature.com/articles/1300202.pdf PDF Version]
*Citation: Mumenthaler, M., Yesavage, J., Taylor, J. et al. Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects. Neuropsychopharmacol 28, 1366–1373 (2003). doi: 10.1038/sj.npp.1300202
*Acknowledgements: This research was supported in part by NIMH Grant 40041; NIA Grant AG17824; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC); the Alcohol Beverage Medical Research Foundation; the Swiss Foundation for Alcohol Research; the Swiss National Science Foundation; and the Medical Research Service of the Department of Veterans Affairs.
*Keywords: cholinergic agents, ethanol, cognition, psychomotor performance, psychopharmacology, aerospace medicine

===1996 [https://link.springer.com/article/10.1007/BF02805972 Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers]===
*These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.
*Citation: Foulds, J., Stapleton, J., Swettenham, J. et al. Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacology 127, 31–38 (1996). https://doi.org/10.1007/BF02805972

===1994 [https://link.springer.com/article/10.1007/BF02245346 Smoking and raven IQ]===
*Nicotine has recently been shown to enhance measures of information processing speed including the decision time (DT) component of simple and choice reaction time and the string length measure of evoked potential waveform complexity. Both (DT and string length) have been previously demonstrated to correlate with performance on standard intelligence tests ([[Special:MyLanguage/Abbreviations|'''IQ''']]).
*In this experiment we used the Raven [[Special:MyLanguage/Abbreviations|'''Advanced Progressive Matrices (APM)''']] test. APM scores were significantly higher in the smoking session compared to the non-smoking session, suggesting that nicotine acts to enhance physiological processes underlying performance on intellectual tasks.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/BF02245346 PDF Version]
*Citation: Stough, C., Mangan, G., Bates, T. et al. Smoking and raven IQ. Psychopharmacology 116, 382–384 (1994). doi: 10.1007/BF02245346
*Key words: Intelligence, APM, Nicotine, Smoking Cholinergic system

===1992 [https://pubmed.ncbi.nlm.nih.gov/1579636/ Nicotine as a cognitive enhancer]===
*Nicotine improves attention in a wide variety of tasks in healthy volunteers.
*Nicotine improves immediate and longer term memory in healthy volunteers.
*Nicotine improves attention in patients with probable Alzheimer's Disease.
*While some of the memory effects of nicotine may be due to enhanced attention, others seem to be the result of improved consolidation as shown by post-trial dosing.
*[https://sci-hub.st/10.1016/0278-5846(92)90069-q PDF Version]
*Citation: Warburton DM. Nicotine as a cognitive enhancer. Prog Neuropsychopharmacol Biol Psychiatry. 1992 Mar;16(2):181-91. doi: 10.1016/0278-5846(92)90069-q. PMID: 1579636.
*Keywords: acetylcholine, Alzheimer's Disease, attention, cholinergic, memory, nicotine, scopolamine.
 

='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
*See Also: The Inflamation Section

===2025: [https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00167-8 Long COVID – a critical disruption of cholinergic neurotransmission?]===
*Conclusions: "A review of the literature indicates that a significant disruption of cholinergic neurotransmission might be a central issue for both LC/ME/CFS and PVS. The hypothesis of a viral blockade of nAChRs and the possibility of a competitive reversal of this blockade by LDTN has been corroborated by highly promising results in the broad application of this method to numerous patients. Randomized controlled trials are necessary to determine whether these preliminary results can be substantiated by evidence. However, LDTN application provides many patients with a method that offers a high probability of symptom relief with only minor side effects and represents an affordable therapeutic intervention for the majority of people affected worldwide. Furthermore, dose-finding studies are required to develop individually adapted therapy regimens with regard to dosage and duration of therapy."
*Citation: Leitzke, M., Roach, D.T., Hesse, S. et al. Long COVID – a critical disruption of cholinergic neurotransmission?. Bioelectron Med 11, 5 (2025). https://doi.org/10.1186/s42234-025-00167-8

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===
* States the obvious: the exposure (smoke vs. nicotine and dose need to be characterised correctly).
* Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.
* Salehi Z, Motlagh Ghoochani BFN, Hasani Nourian Y, Jamalkandi SA, Ghanei M. Allergy Asthma Clin Immunol. 2023 Jun 1;19(1):49. doi: 10.1186/s13223-023-00797-0. PMID: 37264452 Review.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36650574/ Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?] ===
* Nicotine COVID/SARS-CoV-2 interaction mystery takes another turn.
* Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh).
* We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.
*In all four of the cases we studied, transcutaneous use of nicotine led to a near immediate improvement in symptoms and rapid restitutio ad integrum. The course of symptom improvement was as distinct as the clinical presentation of post-COVID-19 syndrome in each patient.
*Citation: Leitzke M. Bioelectron Med. 2023 Jan 18;9(1):2. doi: 10.1186/s42234-023-00104-7. PMID: 36650574 Free PMC article.

===2023: [https://www.nature.com/articles/s41598-023-45072-9 Treatment of 95 post-Covid patients with SSRIs]===
*To stick nicotine patches helps PCS (post-COVID syndrome) patients. This may be not only because nicotine is a nicotinic receptor agonist and therefore an opponent of these poisonous metabolites, but nicotine is a strong acetylcholine (ACh) agonist as well.
*Citation: Rus, C.P., de Vries, B.E.K., de Vries, I.E.J. et al. Treatment of 95 post-Covid patients with SSRIs. Sci Rep 13, 18599 (2023). https://doi.org/10.1038/s41598-023-45072-9

===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183099/ Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials]===
* Studies show that the penetration of SARS-CoV-2 into upper respiratory tract, bronchial and pulmonary cells involve transmembrane receptor ACE2, which probably interacts with acetylcholine nicotinic receptors of the α7 subtype. The mechanism of the interactions remains hypothetical.
* Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
* Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.
* Excessive secondary cytokine reaction plays a role in the mortality associated with COVID. One of the hypotheses to explain the effect of nicotine on the occurrence of severe forms of COVID and death is based on the loss of the downregulation of the parasympathetic nervous system, which exerts an inhibitory effect on cytokine storm, especially in the lung and digestive tract. The α 7-type nicotinic receptors are part of this chain of reaction.
* B. Dautzenberg, A. Levi, M. Adler, and R. Gaillardc. Respir Med Res. 2021 Nov; 80: 100844. Published online 2021 Jun 7. doi: 10.1016/j.resmer.2021.100844 PMCID: PMC8183099 PMID: 34153704

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
*Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
*Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.

===2020: [https://www.sciencedirect.com/science/article/pii/S2214750020302924 Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system]===
*Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.
*Citation: Farsalinos K, Niaura R, Le Houezec J, Barbouni A, Tsatsakis A, Kouretas D, Vantarakis A, Poulas K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep. 2020 Apr 30;7:658-663. doi: 10.1016/j.toxrep.2020.04.012. PMID: 32355638; PMCID: PMC7192087.

=== 2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679833/ Mitochondria as a possible target for nicotine action] ===

* See also this twitter thread for detailed information on possible mechanisms. https://x.com/angryhacademic/status/1741968457296490977?s=20
* This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design.
* The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.
* J Bioenerg Biomembr. 2019; 51(4): 259–276. Published online 2019 Jun 13. doi: 10.1007/s10863-019-09800-z PMCID: PMC6679833 PMID: 31197632

='''Digestive Tract / Bowel'''=
===2024: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntae193/7727428 The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis]===
*"Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients."
**Citation: Kastratovic N, Markovic V, Arsenijevic A, Volarevic A, Zdravkovic N, Zdravkovic M, Brankovic M, Gmizic T, Harrell CR, Jakovljevic V, Djonov V, Volarevic V. The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis. Nicotine Tob Res. 2024 Aug 5:ntae193. doi: 10.1093/ntr/ntae193. Epub ahead of print. PMID: 39101540.
***Paywalled, unable to view funding/COI

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S000927971931734X Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model]===
*Animal study
*Conclusion: "Taken together, we demonstrated that nicotine inhibits apoptosis and proliferation by modulating AMPK/mTOR pathway-mediated autophagy and improves colitis severity in the DSS-induced UC mouse model. These findings provide new insights into the mechanism of nicotine treatment on UC autophagy. Further exploration of the mechanism of nicotine in autophagy and targeting factors might be considered a new approach for ulcerative colitis treatment."
*[https://sci-hub.st/10.1016/j.cbi.2020.108943 PDF Full paper]
**Citation: Gao Q, Bi P, Luo D, Guan Y, Zeng W, Xiang H, Mi Q, Yang G, Li X, Yang B. Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model. Chem Biol Interact. 2020 Feb 1;317:108943. doi: 10.1016/j.cbi.2020.108943. Epub 2020 Jan 10. PMID: 31926917.
***Acknowledgement: This work was supported by the Yunnan Key Laboratory of Tobacco Chemistry Project [Grant No. 2017539200340397].

===2018 [https://academic.oup.com/jleukbio/article-abstract/104/5/1013/6935503 Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment]===
*Animal/Cell study
*These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM-1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC.
*[https://sci-hub.st/10.1002/JLB.3A0717-304R PDF Full paper]
**Citation: Maruta K, Watanabe C, Hozumi H, Kurihara C, Furuhashi H, Takajo T, Okada Y, Shirakabe K, Higashiyama M, Komoto S, Tomita K, Nagao S, Ishizuka T, Miura S, Hokari R. Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. J Leukoc Biol. 2018 Nov;104(5):1013-1022. doi: 10.1002/JLB.3A0717-304R. Epub 2018 Jun 14. PMID: 29901817.
***Acknowledgement: This research was supported by grants from the National Defense Medical College, by Grants-in-aid for the Intractable Diseases Project of the Ministry of Health, Labour, and Welfare of Japan, and by Grantsin-aid for Scientific Research from the Japanese Ministry of Education (2646080).

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533410/ Novel Insights on the Effect of Nicotine in a Murine Colitis Model]===
*Animal study
*Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-α.
**Citation: AlSharari SD, Akbarali HI, Abdullah RA, Shahab O, Auttachoat W, Ferreira GA, White KL, Lichtman AH, Cabral GA, Damaj MI. Novel insights on the effect of nicotine in a murine colitis model. J Pharmacol Exp Ther. 2013 Jan;344(1):207-17. doi: 10.1124/jpet.112.198796. Epub 2012 Oct 31. PMID: 23115221; PMCID: PMC3533410.
***Acknowledgement: This work was supported by National Institutes of Health [Grants DA-019377; (to M.I.D.) and DK 046367] (to H.I.A.).

===2012 [https://journals.physiology.org/doi/full/10.1152/ajpgi.00411.2011 Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation]===
*Animal study
*"In summary, in an acute and postinflammatory model of colitis, we demonstrated that nAChRs mediate suppression of hyperexcitability of colonic sensory. The present study also highlights the potential of in vivo treatment with nicotine towards its antinociceptive effects in colonic inflammation."
**Citation: Abdrakhmanova GR, Kang M, Imad Damaj M, Akbarali HI. Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G740-7. doi: 10.1152/ajpgi.00411.2011. Epub 2012 Jan 12. PMID: 22241859; PMCID: PMC3330777."
***Acknowledgement: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-046367 (to H. I. Akbarali).

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2008 [https://www.hindawi.com/journals/grp/2008/237185/ Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study]===
*Smoking has a detrimental effect in [[Special:MyLanguage/Abbreviations|'''Crohn's disease (CD)''']], but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits [[Special:MyLanguage/Abbreviations|'''ulcerative colitis (UC)''']], and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis.
*In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.
*[http://downloads.hindawi.com/journals/grp/2008/237185.pdf PDF Version]
**Citation: J. R. Ingram, J. Rhodes, B. K. Evans, and G. A. O. Thomas, Hindawi Publishing Corporation, Gastroenterology Research and Practice, Volume 2008, Article ID 237185, 6 pages, doi:10.1155/2008/237185
***Acknowledgements: J. R. Ingram was supported by the Gastrointestinal Foundation Trust. SLA Pharma gave financial support to the project. The authors are indebted to Dr. J. T. Green (of Cardiff and Vale Hospitals Trust) who referred patients, and to Professor G. T. Williams (GTW) who performed all histological assessments.

===2004 [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full Transdermal nicotine for induction of remission in ulcerative colitis]===
*Ulcerative colitis is largely a disease of nonsmokers and patients who have quit smoking. Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis.
*[https://sci-hub.st/https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full PDF Version]
**Citation: McGrath, J., McDonald, J. W., & MacDonald, J. K. (2004). Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004722.pub2
***Acknowledgements: Funding for the IBD/FBD Review Group (October 1, 2005 - September 30, 2010) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch; the Canadian Agency for Drugs and Technologies in Health (CADTH); and the CIHR Institutes of Health Services and Policy Research; Musculoskeletal Health and Arthritis; Gender and Health; Human Development, Child and Youth Health; Nutrition, Metabolism and Diabetes; and Infection and Immunity. Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12072594/ Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice]===
*Animal Study
*Conclusions: (1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides.
*[https://sci-hub.st/10.1097/00042737-200206000-00005 PDF of full paper]
**Citation: Eliakim R, Fan QX, Babyatsky MW. Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice. Eur J Gastroenterol Hepatol. 2002 Jun;14(6):607-14. doi: 10.1097/00042737-200206000-00005. PMID: 12072594.

===1999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/ Nicotine treatment for ulcerative colitis]===
*No withdrawal symptoms suggesting nicotine addiction have been reported either after 4–6 weeks of therapy in short-term studies, or after a period of up to 6 months in the only long-term study available
*It can be concluded from these data that transdermal nicotine alone has limited efficacy in active ulcerative colitis and is ineffective as maintenance treatment. On the other hand, if administered in combination with mesalazine, nicotine is superior to placebo in promoting clinical remission of ulcerative colitis of mild to moderate degree, may represent an efficacious alternative to steroids in selected cases and, when effective, seems to exert a longer-lasting therapeutic effect than prednisone.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/pdf/bcp0048-0481.pdf PDF Version]
**Citation: Guslandi M. Nicotine treatment for ulcerative colitis. Br J Clin Pharmacol. 1999 Oct;48(4):481-4. doi: 10.1046/j.1365-2125.1999.00039.x. PMID: 10583016; PMCID: PMC2014383.
***No funding/COI information

===1996 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398677/ The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.]===
*Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial deterrent of UC and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.
*[https://sci-hub.st/10.1136/pgmj.72.854.714 PDF Version]
**Citation: Birtwistle J. The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis. Postgrad Med J. 1996 Dec;72(854):714-8. doi: 10.1136/pgmj.72.854.714. PMID: 9015463; PMCID: PMC2398677.

===1996: [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of ulcerative colitis.
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1994: [https://pubmed.ncbi.nlm.nih.gov/8114833/ Transdermal nicotine for active ulcerative colitis]===
*The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.
**Citation: Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994 Mar 24;330(12):811-5. doi: 10.1056/NEJM199403243301202. PMID: 8114833.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against ulcerative colitis (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Down's Syndrome'''=
===2001: [https://link.springer.com/chapter/10.1007/978-3-7091-6262-0_19 Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome]===
*To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5–31 years) received placebo and a single dose of transdermal nicotine (5mg patch) over 2h in a single-blind, within-subjects repeated measures design.
*Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.
*Citation: Bernert G., Sustrova M., Sovcikova E., Seidl R., Lubec G. (2001) Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. In: Lubec G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_19

===2000 [https://pubmed.ncbi.nlm.nih.gov/11052587/ Effects of transdermal nicotine on cognitive performance in Down's syndrome]===
*We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalizable because of small numbers.
*[https://sci-hub.st/10.1016/S0140-6736(00)02848-8 PDF Version]
*Seidl R, Tiefenthaler M, Hauser E, Lubec G. Effects of transdermal nicotine on cognitive performance in Down's syndrome. Lancet. 2000 Oct 21;356(9239):1409-10. doi: 10.1016/S0140-6736(00)02848-8. PMID: 11052587.
*Acknowledgements: We thank Pharmacia-Upjohn, Uppsala, Sweden, for providing transdermal nicotine patches. This study was supported by the Red Bull Company, Salzburg.
 

='''Dyskinesia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
*In summary, our data show that nicotine treatment decreases haloperidol-induced VCMs [vacuous chewing movements] in an established rat model of tardive dyskinesia. The demonstration that nicotine removal leads to a return of VCMs, whereas nicotine re-exposure reduced haloperidol-induced VCMs, suggests a causal relationship. These data have clinical applications for the treatment of tardive dyskinesias associated with long-term antipsychotic treatment using nicotine.
**Citation: Bordia T, McIntosh JM, Quik M. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. J Pharmacol Exp Ther. 2012 Mar;340(3):612-9. doi: 10.1124/jpet.111.189100. Epub 2011 Dec 5. PMID: 22144565; PMCID: PMC3286320.
***Acknowledgement: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS47162, NS59910]; and the National Institutes of Health National Institute of Mental Health [Grant MH53631]
 

='''Dystonia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

='''Endurance / Exercise / Athletic Performance'''=

===2024 Article: [https://web.archive.org/web/20241002001111/https://www.golfdigest.com/story/tour-pros-little-helper-does-nicotine-create-a-competitive-advantage Tour Pro’s Little Helper: Does nicotine create a competitive advantage?]===
*"In all, we talked to nearly 100 pro golfers to learn more about the popularity and usage patterns of nicotine on the major professional tours. Some told us they turn to tobacco or nicotine products for an energy boost; others say it helps them concentrate or feel relaxed. But for many, it’s just about keeping on."

===2023 [https://www.mdpi.com/1660-4601/20/2/1009 The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study]===
*The lower perception of pain intensity that we reported after the 8 mg nicotine dose application might be an important factor that affects performance. However, we did not report any improvement in physical performance parameters.
**Citation: Bartík P, Šagát P, Pyšná J, Pyšný L, Suchý J, Trubák Z, Petrů D. The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study. Int J Environ Res Public Health. 2023 Jan 5;20(2):1009. doi: 10.3390/ijerph20021009. PMID: 36673765; PMCID: PMC9859273.
***Acknowledgement: The authors would like to acknowledge the support of Prince Sultan University for paying the article processing charges (APC) of this publication. This study was conducted by the SSDRL research group.

===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745004/ Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players]===
*Our HRV and salivary analysis revealed that nicotine could induce endocrine and sympathetic nerve activity in healthy male baseball players who had never smoked. Compared with the placebo group, the nicotine group exhibited enhanced cognitive function (an average decrease in motor reaction time of 11.14%; an average decrease in motor reaction time of 5.72%) and baseball-hitting performance (an average increase of 34.69%), and small effect sizes were observed for these results. However, muscle strength did not increase after nicotine intake.
**Citation: Fang SH, Lu CC, Lin HW, Kuo KC, Sun CY, Chen YY, Chang WD. Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players. Int J Environ Res Public Health. 2022 Jan 4;19(1):515. doi: 10.3390/ijerph19010515. PMID: 35010774; PMCID: PMC8745004.
***Acknowledgement: Study was supported by the Ministry of Science and Technology in Taiwan (No: MOST 107-2410-H-028-002-MY2 and MOST 109-2410-H-028-009-MY3).

===2022 [https://www.tandfonline.com/doi/full/10.1186/s12970-021-00413-9 Nicotine supplementation enhances simulated game performance of archery athletes]===
*In summary, these results indicated that 2-mg nicotine gum supplementation enhanced cognitive function, decreased saliva α-amylase activity and HRV through stimulating the sympathetic adrenergic system. More importantly, the archery scores were significantly increased after nicotine supplementation.
**Citation: Hung BL, Chen LJ, Chen YY, Ou JB, Fang SH. Nicotine supplementation enhances simulated game performance of archery athletes. J Int Soc Sports Nutr. 2021 Feb 18;18(1):16. doi: 10.1186/s12970-021-00413-9. PMID: 33602279; PMCID: PMC7890628.
***Acknowledgement: Funded by the Taiwan Ministry of Science and Technology (MOST104–2628-H-028-001-MY2).

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236038/ A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males]===
*The present study has demonstrated that low-dose (2 mg) nicotine gum increases leg extensor torque, but counter-movement jump and anaerobic capacity during WAnT remained unchanged when compared to a placebo, whilst there were minimal effects of the 4-mg nicotine gum on the performance parameters measured. Together with our previous observation [24], these results indicate that nicotine per se can improve exercise endurance and muscular strength, something that WADA should continue to monitor alongside patterns of (mis)use.
**Citation: Mündel T, Machal M, Cochrane DJ, Barnes MJ. A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males. Sports Med Open. 2017 Dec;3(1):5. doi: 10.1186/s40798-016-0074-8. Epub 2017 Jan 13. PMID: 28092056; PMCID: PMC5236038.
***Acknowledgement: This study was funded in part by a grant from the World Anti-Doping Agency.

===2006 [https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2006.033373 Effect of transdermal nicotine administration on exercise endurance in men]===
*Nicotine improved exercise endurance by 17 ± 7%, and in the absence of any effect on the usual peripheral markers, such as ventilation, heart rate and blood metabolites, we conclude that nicotine prolongs endurance by a central mechanism that may involve nicotinic receptor activation and/or altered activity of dopaminergic pathways.
*[https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2006.033373 PDF Version]
**Citation: Mündel T, Jones DA. Effect of transdermal nicotine administration on exercise endurance in men. Exp Physiol. 2006 Jul;91(4):705-13. doi: 10.1113/expphysiol.2006.033373. Epub 2006 Apr 20. PMID: 16627574.
 

='''Eyes - Ocular - Vision'''=
==Myopia (short-sighted, near-sighted)==
===2024 [https://iovs.arvojournals.org/article.aspx?articleid=2800816 Administration of Nicotine Can Inhibit Myopic Growth in Animal Models]===
*Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia.
**Citation: Thomson K, Karouta C, Ashby R. Administration of Nicotine Can Inhibit Myopic Growth in Animal Models. Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):29. doi: 10.1167/iovs.65.11.29. PMID: 39292451; PMCID: PMC11412605.
***Acknowledgement: Funded by ANU Connect Ventures through a Discovery Translation Fund grant (Project ID: DTF311).
 

='''Hashimoto's disease (Hashimoto thyroiditis)'''=
*[https://www.hopkinsmedicine.org/health/conditions-and-diseases/hashimotos-thyroiditis Hashimoto's Thyroiditis] "is when your thyroid gland becomes irritated or inflamed. Hashimoto thyroiditis is the most common type of this health problem. It may also be called chronic autoimmune thyroiditis. This thyroiditis is an autoimmune disease. It occurs when your body makes antibodies that attack the cells in your thyroid. The thyroid gland becomes overrun with white blood cells and becomes scarred. This makes the gland feel firm and rubbery. The thyroid then can’t make enough of the thyroid hormone."

===2020: [https://www.endocrine-abstracts.org/ea/0070/ea0070oc8.4?_ga=2.114580999.1434360570.1735281186-102848752.1735281184 Cigarette smoking and the risk to develop symptoms of Hashimoto’s thyroiditis]===
*"In patients who had discontinued smoking at the age of 39 years or more, the diagnosis of HT was predominantly made after the discontinuation of smoking."

===2013: [https://onlinelibrary.wiley.com/doi/10.1111/cen.12222 Smoking and thyroid]===
*"Smoking has distinct associations with thyroid function and size in healthy subjects. It has remarkable and contrasting associations with thyroid function in autoimmune thyroid disease (lower risk of Hashimoto's disease and higher risk of Graves’ disease) and with thyroid size in nodular disease (lower risk of thyroid carcinoma and higher risk of nontoxic goitre and multinodularity). The observed associations likely indicate causal relationships in view of consistent associations across studies, the presence of a dose–response relationship and disappearance of the associations after cessation of smoking. Which mechanisms mediate the many effects of smoking remains largely obscure. Probably, they differ between the various effects. The divergent effects of smoking on the expression of autoimmune thyroid disease are intriguing and reminiscent on the contrasting effects of smoking on inflammatory bowel disease: protective against ulcerative colitis (OR 0·41, 0·34–0·48) but risky for Crohn's disease (OR 1·61, 1·27–2·03)."
*[https://sci-hub.st/10.1111/cen.12222 PDF Full paper]
**Citation: Wiersinga, W. M. (2013). Smoking and thyroid. Clinical Endocrinology, 79(2), 145–151. doi:10.1111/cen.12222
***Acknowledgement: None stated

='''HIV (human immunodeficiency virus)'''=

===2025: [https://www.sciencedirect.com/science/article/abs/pii/S0149763425003495 Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential]===
*"Approximately half of people with HIV (PWH) experience neurocognitive impairment (NCI), despite antiretroviral therapies that have turned what was formerly a death sentence to a chronic illness. No targeted treatments exist for HIV-associated NCI, impacting long-term quality of life. Smoking rates in PWH are nearly double those of the general population, and with evidence for pro-cognitive effects of nicotine, this may reflect self-medication. However, clinical studies yield inconsistent findings-some showing benefits, others reporting harm-likely due to variability in nicotine exposure methods, cognitive testing paradigms, withdrawal states, and confounding comorbidities. In contrast, animal studies offer a more controlled framework to isolate the effects of nicotine. Preclinical models suggest that nicotine may mitigate HIV-associated cognitive deficits by acting on α7 nicotinic acetylcholine receptors (nAChRs), leading to reduced neuroinflammation. These findings highlight the therapeutic potential of targeting nAChRs, though mechanisms remain incompletely understood..."
**Citation: Jha NA, Ayoub SM, Brody AL, Young JW. Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential. Neurosci Biobehav Rev. 2025 Aug 23;177:106348. doi: 10.1016/j.neubiorev.2025.106348. Epub ahead of print. PMID: 40854454.
***Acknowledgement: This work was supported by the National Institutes of Health [grant numbers: R01MH134175 (JWY), R01MH128869 (JWY), R01DA051295 (JWY)]...

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

='''Huntington’s Disease'''=

===2005: [https://pubmed.ncbi.nlm.nih.gov/16140176/ Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats]===
*These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.
*In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.
*[https://sci-hub.se/10.1016/j.brainresbull.2005.06.024 PDF Version]
**Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.
 

='''Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis''' (See Also: Allergies/Hayfever/Histamines)=
*[https://www.nhlbi.nih.gov/health/hypersensitivity-pneumonitis Hypersensitivity pneumonitis] is a rare immune system disorder that affects the lungs. This disease is also called bird or pigeon fancier’s lung, farmer’s lung, hot tub lung, cheese worker's lung, Bagassosis, mushroom worker's lung, malt worker's lung, or humidifier lung.
*[https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity pneumonitis] (HP) classified as an interstitial lung disease is characterized by a complex immunological reaction of the lung parenchyma in response to repetitive inhalation of a sensitized allergen.

===2023: [https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity Pneumonitis]===
*Cigarette smoking seems to protect from developing clinically significant HP likely due to nicotine inhibiting macrophage activation and lymphocyte proliferation.
*However, smokers who develop HP have been shown to have a more severe course and higher mortality.
**Citation: Chandra D, Cherian SV. Hypersensitivity Pneumonitis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499918/

===2007: [https://academic.oup.com/qjmed/article-abstract/100/4/233/2258683?redirectedFrom=fulltext Extrinsic allergic alveolitis: incidence and mortality in the general population]===
*We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at ∼0.9 cases per 100 000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39–0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05–4.33).
**Citation: M. Solaymani-Dodaran, J. West, C. Smith, R. Hubbard, Extrinsic allergic alveolitis: incidence and mortality in the general population, QJM: An International Journal of Medicine, Volume 100, Issue 4, April 2007, Pages 233–237, https://doi.org/10.1093/qjmed/hcm008

===2002: [https://www.atsjournals.org/doi/10.1164/rccm.200210-1154OC Inhibitory Effect of Nicotine on Experimental Hypersensitivity Pneumonitis In Vivo and In Vitro]===
*Animal study
*Results of this study show that nicotine reduces the alveolar inflammatory response to S. rectivirgula antigen and affects some AM (stimulated with LPS or S. rectivirgula) functions in vitro. This influence could be, at least in part, responsible for the protection that smokers have against development of HP. Because nicotine is effective in the treatment of ulcerative colitis, it could also be of interest in the treatment of HP and other pulmonary inflammatory diseases.
**Citation: Blanchet MR, Israël-Assayag E, Cormier Y. Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med. 2004 Apr 15;169(8):903-9. doi: 10.1164/rccm.200210-1154OC. Epub 2003 Dec 30. PMID: 14701707.

===1992: [https://pubmed.ncbi.nlm.nih.gov/1344064/ Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum]===
*It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.
**Citation: Arima K, Ando M, Ito K, Sakata T, Yamaguchi T, Araki S, Futatsuka M. Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum. Arch Environ Health. 1992 Jul-Aug;47(4):274-8. doi: 10.1080/00039896.1992.9938361. PMID: 1344064.

===1987: [https://pubmed.ncbi.nlm.nih.gov/3499342/ Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking]===
*Farmer's lung was only slightly more common among atopic than among non-atopic subjects and twice as common among non-smokers as among smokers.
**Citation: Terho EO, Husman K, Vohlonen I. Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking. Eur J Respir Dis Suppl. 1987;152:19-28. PMID: 3499342.

===1977: [https://pmc.ncbi.nlm.nih.gov/articles/PMC470791/ Extrinsic allergic alveolitis: a disease commoner in non-smokers.]===
*In the literature of extrinsic allergic alveolitis non-smokers predominate in those papers in which smoking habits are recorded (Hapke et al., 1968; Schlueter et al., 1969; Schofield et al., 1976). Studies of the prevalence of precipitating antibodies against Micropolyspora faeni in farmers have shown that they are detected significantly more often in non-smokers than in smokers (Morgan et al., 1975).
**Citation: Warren CP. Extrinsic allergic alveolitis: a disease commoner in non-smokers. Thorax. 1977 Oct;32(5):567-9. doi: 10.1136/thx.32.5.567. PMID: 594937; PMCID: PMC470791.
 

='''Hypothyroidism'''=

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated
 

='''Inflammation'''=

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871277/ Effect of Nicotine on Immune System Function]===
*Despite the completely destructive and harmful effects of cigarette smoke, nicotine via stimulation of the α7 receptor can promote the anti-inflammatory benefits on the immune system. However, these effects depend on the concentration, and administration methods are different and sometimes contradictory. It can be used successfully to treat or inhibit autoimmune diseases. Although the exact mechanism of this treatment is unknown, it appears to involve inhibiting downstream intracellular pathways that lead to the secretion of pre-inflammatory cytokines.
**Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
**Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483
***Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
**Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.
***Acknowledgement: All authors have declared that no financial support was received from any organization for the submitted work.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
**Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.
***Acknowledgement: This work was supported by University of Castilla-La Mancha Research Programme 2020-GRIN-28705.

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila and Chlamydia pneumonia infection...
**Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2011 [https://pubmed.ncbi.nlm.nih.gov/21691078/ Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells]===
*In summary, we showed that nicotine could suppress TNF-α expression mainly through activation of the α7 nAChR subunit, which inhibited the MyD88/IκBα/NFκB signaling pathway in HBE16 airway epithelial cells. These findings may provide new information on the potential pharmacological effects of nicotine and nAChR in the treatment of respiratory inflammatory diseases. Further research on nicotine and nAChRs may provide more evidence for the treatment of inflammatory diseases and the development of related drugs.
*[https://www.karger.com/Article/Pdf/329982 PDF Version]
**Citation: Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982
***Acknowledgement: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
**Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
***Acknowledgement: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.

===2008 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693390/ Neuronal Nicotinic Alpha7 Receptors Modulate Inflammatory Cytokine Production in the Skin Following Ultraviolet Radiation]===
*Animal study
*Cytokine responses to UV in mice administered chronic oral nicotine, a nAChR agonist, were reduced... These results demonstrate that nAChRα7 can participate in modulating a local pro-inflammatory response in the absence of parasympathetic innervation.
**Citation: Osborne-Hereford AV, Rogers SW, Gahring LC. Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation. J Neuroimmunol. 2008 Jan;193(1-2):130-9. doi: 10.1016/j.jneuroim.2007.10.029. PMID: 18077004; PMCID: PMC2693390.
***Acknowledgement: These studies were funded by NIH grants DA015148 and DA018930 (LCG), PO1 HL72903 (LCG, SWR) and the Browning Foundation of Utah.

===2006 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809735/ Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7]===
*Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-α, prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-1α and MIP-1α, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet’s disease and Crohn’s disease. In addition, the nicotinic acetylcholine receptor-α7 (α7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the α7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes.
*These suppressive effects of nicotine were caused at the transcriptional level and were mediated through α7nAChR. Nicotine suppressed the phosphorylation of I-κB, and then inhibited the transcriptional activity of nuclear factor-κB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.
*This supports the therapeutic use of nicotine in some inflammatory diseases; the NF-κB activation pathway is one of the most critical molecular targets of nicotine therapy.
**Citation: Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. 2006 Oct;146(1):116-23. doi: 10.1111/j.1365-2249.2006.03169.x. PMID: 16968406; PMCID: PMC1809735.
 

='''Legionella Pneumophila (Legionnaires' disease)'''=

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''ME/CFS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome'''=
*See Also: COVID (Long COVID)
 

='''Mental Health'''=
*See subcategories below
 
=='''Mental Health - Anxiety'''==
===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated
 

=='''Mental Health - Behavior Issues'''==
*See Also: ADD/ADHD above

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0028390819305003?via%3Dihub Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies]===
*Human and Animal Studies
*Clinical trials and case series report anti-aggressive effects of nicotine. Here we argue that the [[Special:MyLanguage/Abbreviations|'''nAChR''']] system, the molecular basis for the global public health problem of tobacco smoking, may also be a key target for modulation of aggressive behaviors. Future research should aim to clarify which forms of aggression are most strongly affected by nAChR modulation, identify the nAChR subtypes, circuits, and neurobiological mechanisms of nicotine action, and determine whether more selective nAChR-active agents can replicate or improve the serenic effects of nicotine, especially with chronic dosing. Given the prevalence of aggressive behaviors across neuropsychiatric disorders affecting the very young to the very old, these studies have the potential to have a significant impact on public health.
*[https://sci-hub.st/https://doi.org/10.1016/j.neuropharm.2019.107929 PDF Version]
*Citation: Alan S. Lewis, Marina R. Picciotto, Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies, Neuropharmacology, Volume 167, 2020, 107929, ISSN 0028-3908, doi: 10.1016/j.neuropharm.2019.107929.
*Acknowledgements: This work was supported by National Institutes of Health grants MH116339 (A.S.L.), MH077681 and DA14241 (M.R.P.).

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
*Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
*Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).
 

=='''Mental Health - Depression'''==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15950 The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study]===
*In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.
*Citation: Yebo Yu, Fan Yang, Mingqi Fu, Farooq Ahmed, Muhammad Shahid, Jing Guo, Relationship Between Work-Family Conflict and Depressive Symptoms Among Male Firefighters in China, Journal of Occupational & Environmental Medicine, 10.1097/JOM.0000000000002759, 65, 4, (337-343), (2022).

===2021 [https://www.sciencedirect.com/science/article/abs/pii/S0376871621005676 Adolescent depression symptoms and e-cigarette progression]===
*Depression symptoms predicted more rapid e-cigarette progression in adolescents.
*E-cigarette use was not associated with an escalation in depression symptoms.
*E-cigarette use was not related to the development of depression symptoms over time.
*Must pay to view PDF
*Citation: Afaf F. Moustafa, Shannon Testa, Daniel Rodriguez, Stephen Pianin, Janet Audrain-McGovern, Adolescent depression symptoms and e-cigarette progression, Drug and Alcohol Dependence, Volume 228, 2021, 109072, ISSN 0376-8716, doi.org/10.1016/j.drugalcdep.2021.109072.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2000 [https://www.sciencedirect.com/science/article/abs/pii/S0091305700002057 The Effects of Nicotine on Neural Pathways Implicated in Depression: A Factor in Nicotine Addiction?]===
*It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine.
*[https://sci-hub.st/10.1016/S0091-3057(00)00205-7 PDF Version]
*Citation: Balfour, D. J. ., & Ridley, D. L. (2000). The Effects of Nicotine on Neural Pathways Implicated in Depression. Pharmacology Biochemistry and Behavior, 66(1), 79–85. doi:10.1016/s0091-3057(00)00205-7

===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0149763417301793 Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression]===
*Nicotine improves cognitive performance in clinical and preclinical studies.
*Nicotine may also benefit depressive symptoms and depressive behavior.
*Cognitive and mood benefits may be mediated by nicotinic effect on neural networks.
*Nicotine’s effects on networks may reverse network changes seen in depression.
*Improvement to mood and cognition may particularly benefit older depressed adults.
*Both preclinical and clinical studies support that nicotine and other nAChR agonists can improve depressive behavior, mood, and cognitive performance. nAChR agonists also demonstrate neuropharmacologic effects that oppose the intrinsic network alterations reported in MDD. Through modulation of intrinsic functional networks, nAChR agonists may reduce depressive symptoms, enhance emotional regulation ability, and improve cognitive deficits common in LLD. For these reasons, we propose nAChR agonists as a potential novel treatment for the mood and cognitive symptoms of LLD.
*[https://sci-hub.st/10.1016/j.neubiorev.2017.08.018 PDF Version]
*Citation: Gandelman, J. A., Newhouse, P., & Taylor, W. D. (2018). Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression. Neuroscience & Biobehavioral Reviews, 84, 289–298. doi:10.1016/j.neubiorev.2017.08.0
*Acknowledgement: Supported by NIH grants K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences.

===2018 [https://pubmed.ncbi.nlm.nih.gov/29795403/ Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder]===
*In [[Special:MyLanguage/Abbreviations|'''MDD''']], acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD.
*[https://sci-hub.st/10.1038/s41386-018-0069-x PDF Version]
*Citation: Janes AC, Zegel M, Ohashi K, Betts J, Molokotos E, Olson D, Moran L, Pizzagalli DA. Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. Neuropsychopharmacology. 2018 Nov;43(12):2445-2451. doi: 10.1038/s41386-018-0069-x. Epub 2018 Apr 19. PMID: 29795403; PMCID: PMC6180119.
*Acknoledgements: This project was supported by the National Institute on Drug Abuse grants K10 DA029645 and K02 DA042987 (ACJ). DAP was partially supported by National Institute of Mental Health grant R37 MH068376. Over the past 3 years, DAP has received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Pfizer and Posit Science, for activities unrelated to the current research.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/ Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Non-Smokers with Late-Life Depression]===
*[[Special:MyLanguage/Abbreviations|Late '''Life Depression (LLD)''']] is characterized by poor antidepressant response and cognitive dysfunction. Late life depression has no currently approved treatment that improves both its mood and cognitive symptoms.
*We observed robust response (86.7%) and remission rates (53.3%). There was a significant decrease in MADRS (Montgomery-Asberg Depression Rating scale) over the study, with improvement seen as early as three weeks. We also observed improvement in apathy and rumination. We did not observe improvement on the CPT (Conners Continuous Performance Test), but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/pdf/nihms965043.pdf PDF Version]
*Citation: Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137. PMID: 30192444; PMCID: PMC6129985.
*Acknowledgements: This research was supported by NIH grant K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. The sponsor provided funding for the study but did not influence the design or conduct of the study.

===2006 [https://pubmed.ncbi.nlm.nih.gov/16977477/ Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial]===
*These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
*[https://sci-hub.st/10.1007/s00213-006-0516-y PDF Version]
*Citation: McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2006 Nov;189(1):125-33. doi: 10.1007/s00213-006-0516-y. Epub 2006 Sep 15. PMID: 16977477.
*Acknowledgement: This research was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Dr. Rose is an inventor named on several nicotine patch patents and receives royalties from sales of certain nicotine patches.

===2002 [https://pubmed.ncbi.nlm.nih.gov/11995405/ Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients]===
*Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration.
*Citation: Salin-Pascual RJ. Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Rev Invest Clin. 2002 Jan-Feb;54(1):36-40. PMID: 11995405.

===1999 [https://link.springer.com/article/10.1007/s002130050879 Antidepressant effects of nicotine in an animal model of depression]===
*Animal Study
*Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals.
*The data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the [[Special:MyLanguage/Abbreviations|'''FSL''']] rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
*[https://sci-hub.st/https://doi.org/10.1007/s002130050879 PDF Version]
*Citation: Tizabi, Y., Overstreet, D., Rezvani, A. et al. Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142, 193–199 (1999). https://doi.org/10.1007/s002130050879
*Acknowledgements This work was supported in part by the Department of Pharmacology, Howard University, VAMC and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
*Keywords: Key words Nicotine · Nicotinic receptor · FSL and FRL rats · Animal model of depression

===1998 [https://pubmed.ncbi.nlm.nih.gov/9592048/ A novel effect of nicotine on mood and sleep in major depression]===
*Transdermal nicotine patches increased REM sleep in normal volunteers and depressed patients during 4 days of continuous administration. In addition, a significant improvement of mood was observed in depressed patients. Nicotinic mechanisms may be involved in depression. These findings suggest that nicotine receptor activation may be important in major depression and shows for the first time that nicotine patches may be useful in the treatment of depression.
*[https://sci-hub.st/10.1097/00001756-199801050-00012 PDF Version]
*Salín-Pascual RJ, Drucker-Colín R. A novel effect of nicotine on mood and sleep in major depression. Neuroreport. 1998 Jan 5;9(1):57-60. doi: 10.1097/00001756-199801050-00012. PMID: 9592048.
*ACKNOWLEDGEMENT: This work has been supported by the following grants: DGAPA-UNAM IN -200895 to R.J.S-P.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9746444/ Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression]===
*A high frequency of cigarette smoking has been reported among individuals with major depression.
*Results of the visual analog scale and [[Special:MyLanguage/Abbreviations|'''HAM-D''']] showed a significant improvement in depression after the second day of nicotine patches.
*Citation: Salín-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL, Delgado-Parra V. Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry. 1996 Sep;57(9):387-9. PMID: 9746444.

===1996 [https://psycnet.apa.org/record/1996-00468-019 Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.]===
*Depressed smokers relapsed significantly earlier than the nondepressed. Nicotine gum was significantly more effective than placebo gum among all smokers. The benefits of nicotine gum were particularly apparent among the depressed. Only 12.5% of depressed smokers quit successfully with placebo gum for 3 months, whereas 29.5% quit with nicotine gum. Depressed smokers reported more stress, less coping resources, more physical and psychological symptoms, and more frequent smoking in the presence of negative affect than did the nondepressed.
*[https://sci-hub.st/10.1037/0022-006X.64.4.791 PDF Version]
**Citation: Kinnunen, T., Doherty, K., Militello, F. S., & Garvey, A. J. (1996). Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement. Journal of Consulting and Clinical Psychology, 64(4), 791–798. https://doi.org/10.1037/0022-006X.64.4.791

===1995 [https://pubmed.ncbi.nlm.nih.gov/8619011/ Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients]===
*The main finding of the present study was that nicotine patches induced an increase in REM sleep time in depressed patients without any other changes in sleep variables
*[https://sci-hub.st/10.1007/BF02246496 PDF Version]
*Citation: Salín-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colín R. Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology (Berl). 1995 Oct;121(4):476-9. doi: 10.1007/BF02246496. PMID: 8619011.
*Acknowledgement: This work has been supported in part by FIIRESIN, Fideicomiso-UNAM (to RD-C) and DGAPA-UNAM1N203393 (to RJS-P).

===1993 [https://jamanetwork.com/journals/jamapsychiatry/article-abstract/496026 Nicotine Dependence and Major Depression]===
*There is, then, no evidence in these data that the occurrence of MDD in persons with a prior history of nicotine dependence might have been caused directly by recent persistent smoking.
*[https://sci-hub.st/10.1001/archpsyc.1993.01820130033006 PDF Version]
*Citation: Breslau N, Kilbey MM, Andreski P. Nicotine Dependence and Major Depression: New Evidence From a Prospective Investigation. Arch Gen Psychiatry. 1993;50(1):31–35. doi:10.1001/archpsyc.1993.01820130033006

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement (mood normalization) (other issues and diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

=='''Mental Health - Mental Illness'''==

===2022 [https://academic.oup.com/ntr/article-abstract/24/9/1405/6562456 E-Cigarette Provision to Promote Switching in Cigarette Smokers With Serious Mental Illness—A Randomized Trial]===
*This was the first prospective study to compare e-cigarette provision with assessments only to evaluate the appeal and impact of e-cigarettes on smoking behavior, carbon monoxide exposure, and nicotine dependence among smokers with Severe Mental Illness (SMI) who had tried but were unable to quit and were not currently interested in cessation treatment. The finding that e-cigarette provision led to significant reductions in smoking and carbon monoxide without increasing nicotine dependence has implications for reducing harm not only among the millions of smokers with SMI who struggle to quit, but also for other vulnerable smokers who cannot achieve cessation.
 

=='''Mental Health - OCD (Obsessive Compulsive Disorder)'''==
===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/ Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review]===
*Nicotine may ameliorate OC symptoms in severe, treatment-refractory [[Special:MyLanguage/Abbreviations|'''OCD''']] patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/pdf/12991_2020_Article_309.pdf PDF Version]
*Citation: Piacentino D, Maraone A, Roselli V, Berardelli I, Biondi M, Kotzalidis GD, Pasquini M. Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review. Ann Gen Psychiatry. 2020 Sep 30;19:57. doi: 10.1186/s12991-020-00309-z. PMID: 33014119; PMCID: PMC7528475.
 

=='''Mental Health - PTSD (Post Traumatic Stress Disorder)'''==
===2012 [https://www.hindawi.com/journals/aps/2012/265724/ Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study]===
*Smokers with PTSD report greater NA (Negative Affects) immediately prior to smoking and greater decreases in NA following smoking, and these findings are consistent with the observed patterns of brain activation in the current study. Thus, our findings provide a neurobiological basis that helps explain why individuals with PTSD are at greater risk of smoking and also experience greater difficulty quitting. The present study is not without its limitations. Our sample size was small and was predominately represented by female smokers.
*[https://downloads.hindawi.com/journals/aps/2012/265724.pdf PDF Version]
*Citation: Froeliger, B., Crowell Beckham, J., Feldman Dennis, M., Victoria Kozink, R., & Joseph McClernon, F. (2012). Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study. Advances in Pharmacological Sciences, 2012, 1–6. doi:10.1155/2012/265724
*Acknowledgement: Department of Veterans Affairs or the National Institutes of Health.
 

=='''Mental Health - Schizophrenia'''==
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fpsyt.2022.804055/full Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence]===
*Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
*[https://twitter.com/hbwardMD/status/1487037135299518474 Twitter thread about this study]
**Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055
***Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0149763420305042?via%3Dihub The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review]===
*Cognitive and early sensory alterations are core features of [https://en.wikipedia.org/wiki/Schizophrenia '''schizophrenia''']. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.
*[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 PDF Version]
**Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.

=== 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===
*Animal Study
*“Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
*Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
**Citation: Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)

===2017: [https://pubmed.ncbi.nlm.nih.gov/28441884/ Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging]===
*This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.
**Citation: Smucny J, Tregellas JR. Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging. J Psychopharmacol. 2017 Jul;31(7):801-811. doi: 10.1177/0269881117705071. Epub 2017 Apr 26. PMID: 28441884; PMCID: PMC5963521.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Citation: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===
*The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.
*[https://sci-hub.st/10.1016/j.mehy.2009.02.017 PDF Version]
**Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

===2007: [https://pmc.ncbi.nlm.nih.gov/articles/PMC2702723/ Nicotinic Interactions with Antipsychotic Drugs, Models of Schizophrenia and Impacts on Cognitive Function]===
*Human and Animal study
*Nicotinic receptor systems in the brain are important for a variety of aspects of cognitive function impaired in schizophrenia and aggravated by antipsychotic drugs. Nicotine and selective nicotinic α7 and α4β2 agonists can significantly improve learning, memory and attention. Nicotine and nicotine agonists can reduce some of the cognitive impairments caused by some antipsychotic drugs as well as reduce cognitive impairments seen in the NMDA glutamate blockade animal model of schizophrenia.
**Citation: Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007 Oct 15;74(8):1182-91. doi: 10.1016/j.bcp.2007.07.019. Epub 2007 Jul 20. PMID: 17714691; PMCID: PMC2702723.
***Acknowledgement: Research presented was supported by a grant from the National Institute of Mental Health grant MH64494.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
**Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.
 

='''Movement Disorders (not diagnosis specific)'''=
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/ Role for the nicotinic cholinergic system in movement disorders; therapeutic implications]===
*Animal Study
*Several [[Special:MyLanguage/Abbreviations|'''nAChR''']] subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/pdf/nihms600497.pdf PDF Version]
*Citation: Quik M, Zhang D, Perez XA, Bordia T. Role for the nicotinic cholinergic system in movement disorders; therapeutic implications. Pharmacol Ther. 2014 Oct;144(1):50-9. doi: 10.1016/j.pharmthera.2014.05.004. Epub 2014 May 14. PMID: 24836728; PMCID: PMC4149916.
*Acknowledgements: This work was supported by grants NS59910 and NS 65851 from the National Institutes of Health.
 

='''Multiple Sclerosis - Humans / Experimental Autoimmune Encephalomyelitis (EAE) - Animals'''=

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2015 [https://pubmed.ncbi.nlm.nih.gov/25813705/ Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis]===
*Amimal study
*We found that reduction of ependymal cell proliferation correlated with inflammation in the same area, which was relieved by the administration of nicotine. Further, increased numbers of oligodendrocytes (OLs) were observed after nicotine treatment. These findings give a new insight into the mechanism of how nicotine functions to attenuate EAE.
*[https://sci-hub.st/10.1016/j.neuroscience.2015.03.031 PDF Full Study]
**Citation: Gao Z, Nissen JC, Legakis L, Tsirka SE. Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis. Neuroscience. 2015 Jun 25;297:11-21. doi: 10.1016/j.neuroscience.2015.03.031. Epub 2015 Mar 23. PMID: 25813705; PMCID: PMC4428965.
***Acknowledgement: The work was supported by NMSS PP1815, NIH R01NS42168, NIH IRACDA K12GM102778.

===2015 [https://pubmed.ncbi.nlm.nih.gov/26209886/ Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients]===
*The data obtained highlight the role of α7 receptor subtype in the modulation of anti-inflammatory cytokines also in MS. Moreover the ability of nicotine to up-regulate the expression of α7 receptor subtype in RR-MS patients, indicates that nicotinic receptor stimulation may contribute to down-modulate the inflammation occurred in MS by a positive feedback control of its expression.
*[https://sci-hub.st/10.1016/j.intimp.2015.06.034 PDF Full paper]
**Citation: Reale M, Di Bari M, Di Nicola M, D'Angelo C, De Angelis F, Velluto L, Tata AM. Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients. Int Immunopharmacol. 2015 Nov;29(1):152-7. doi: 10.1016/j.intimp.2015.06.034. Epub 2015 Jul 23. PMID: 26209886.
***Acknowledgement: This work was supported by FISM – Fondazione Italiana Sclerosi Multipla – Cod. 2013/R/25. MDB was supported by fellowship on FISM project 2013/R/25.

===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/ The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components]===
*Animal Study
*Our results show that nicotine reduces the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an [[Special:MyLanguage/Abbreviations|'''EAE/MS''']] therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/pdf/pone.0107979.pdf PDF Version]
**Citation: Gao Z, Nissen JC, Ji K, Tsirka SE. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One. 2014 Sep 24;9(9):e107979. doi: 10.1371/journal.pone.0107979. PMID: 25250777; PMCID: PMC4176721.
***Acknowledgements: This work was supported by National Multiple Sclerosis Society awards CA1044A1 and PP181, National Aeronautics and Space Administration NNA14AB04A and National Institutes of Health R01NS42168 (ST), and National Institutes of Health K12GM102778 to JN.

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.
 

='''Narcolepsy'''=

===2021: [https://www.authorea.com/doi/full/10.22541/au.162126605.51833119 The therapeutic use of medical nicotine in narcolepsy]===
*PDF: [https://www.researchgate.net/profile/Carolina-Diamandis/publication/351648895_The_therapeutic_use_of_medical_nicotine_in_narcolepsy/links/60aa9cb945851522bc10a4c1/The-therapeutic-use-of-medical-nicotine-in-narcolepsy.pdf The therapeutic use of nicotine in narcolepsy]

===2012: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3311418/ Narcolepsy with Cataplexy Masked by the Use of Nicotine]===
*

===2010: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2823281/ A Novel Approach to Treating Morning Sleep Inertia in Narcolepsy]===
*

='''Nicotine Used With Other Substances'''=

===2021 [https://pubmed.ncbi.nlm.nih.gov/34119664/ Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats]===
*Animal Study
*The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA. (Note: AKA ecstasy)
*Citation: Kowsari G, Mehrabi S, Soleimani Asl S, Pourhamzeh M, Mousavizadeh K, Mehdizadeh M. Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats. J Chem Neuroanat. 2021 Jun 10;116:101986. doi: 10.1016/j.jchemneu.2021.101986. Epub ahead of print. PMID: 34119664.

='''Oral / Jaw'''=
===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
*Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).
*Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, [https://en.wikipedia.org/wiki/Edema oedema], and [https://en.wikipedia.org/wiki/Trismus trismus] in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
*Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
*Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444372/ Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program]===
*The results of this study confirm that chewing the tested nicotine replacement gum as recommended in a ‘real world’ active smoking cessation program produces a statistically significant change in the parameter of whitening as measured by change from baseline versus the negative control (Microtab) following 6 weeks in a smoking cessation programme. The Vita® Shade Guide (the secondary outcome measure) supported the trend of stain improvement. These results support the efficacy of the tested nicotine replacement gum in stain reduction, in arresting the progression of tooth stain and in shade lightening.
*Acknowledgement: The study was fully funded by McNeil AB who is the manufacturer of the test and control products. It was designed by McNeil AB in consultation with HW and DOM. The study was run, participants recruited, smoking cessation intervention administered and data collected by the team of research staff at the Oral Health Services Research Centre at University College Cork under the leadership of HW with consultant input from DOM. RK carried out the clinical examinations but was blinded to intervention allocation. The data were analysed by McNeil AB with input from HW and DOM. The study was externally monitored by MDS Pharma Services, UK and conducted to ICH GCP standards. The data were interpreted by HW, DOM and RK. The manuscript was drafted by HW with editorial comment from the other authors. HW decided to submit the manuscript for publication.
*Citation: Whelton H, Kingston R, O'Mullane D, Nilsson F. Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program. BMC Oral Health. 2012 Jun 13;12:13. doi: 10.1186/1472-6831-12-13. PMID: 22695211; PMCID: PMC3444372.
 

='''Pain / Analgesic'''=
===2024: [https://pubmed.ncbi.nlm.nih.gov/39719676/ Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial]===
*Postoperative pain scores at rest and on movement were lower in the nicotine group than in the placebo group at 6 hours, 12 hours, and 24 hours after surgery (P<0.05). Postoperative morphine consumption was lower in the nicotine group than in the placebo group (9.92 ± 4.0 vs. 15.9 ± 5.0 mg, respectively; P=0.0002).
**Citation: Maheshwari A, Gupta M, Garg B, Singh AK, Khanna P. Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial. J Neurosurg Anesthesiol. 2024 Dec 25. doi: 10.1097/ANA.0000000000001022. Epub ahead of print. PMID: 39719676.
***Acknowledgement: Paywalled, can not access

===2023: [https://pubmed.ncbi.nlm.nih.gov/37132069/ Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study]===
*Perioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.
**Citation: Zhu C, Bi Y, Wei K, Tao K, Hu L, Lu Z. Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study. Addiction. 2023 Aug;118(8):1579-1585. doi: 10.1111/add.16224. Epub 2023 May 19. PMID: 37132069.
***Acknowledgement: Shanghai Municipal Science and Technology Commission. Grant Number: 17411960400

===2023: [https://www.mdpi.com/1424-8247/16/12/1665 The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis]===
*Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
**Citation: Luo Y, Yang Y, Schneider C, Balle T. The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis. Pharmaceuticals. 2023; 16(12):1665. https://doi.org/10.3390/ph16121665
***Acknowledgement: This work was funded by the Australian Research Council LP160100560.

===2023 [https://www.sciencedirect.com/science/article/abs/pii/S0014299923000298?via%3Dihub Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron]===
*Animal Study
*Nicotine-induced antinociception was inhibited by intrathecal pre-treatment with yohimbine, an α2 adrenergic receptor antagonist. These results indicated that nicotine may suppress BCAO-induced mechanical hypersensitivity through the activation of the descending pain control system via orexin neurons.
**Citation: Nakamoto, K., Matsuura, W., & Tokuyama, S. (2023). Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron. European journal of pharmacology, 175518. Advance online publication. https://doi.org/10.1016/j.ejphar.2023.175518
***Acknowledgement: This work was supported by the Smoking Research Foundation (FP01807092).

===2023: [https://pubmed.ncbi.nlm.nih.gov/36947193/ Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials]===
*Perioperative use of NP significantly improved postoperative pain, even when opioids were administered or prescribed. Nevertheless, the clinical relevance should be interpreted with caution, owing to the effect sizes of the summary measures and methodological issues. The analgesic potential of NP as an adjuvant therapy to regulate pain and acute inflammation may offer certain clinical advantages, thus warranting further investigation.
**Citation: da Silva Barbirato D, de Melo Vasconcelos AF, Dantas de Moraes SL, Pellizzer EP, do Egito Vasconcelos BC. Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials. Eur J Clin Pharmacol. 2023 May;79(5):589-607. doi: 10.1007/s00228-023-03475-7. Epub 2023 Mar 22. PMID: 36947193.
***Acknowledgement: Paywalled, can't access

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, oedema, and trismus in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
**Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
***Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/ Acute Analgesic Effects of Nicotine and Tobacco in Humans: A Meta-Analysis]===
*Pain and tobacco smoking are both highly prevalent and comorbid conditions, current smoking has been associated with more severe chronic pain and physical impairment, and acute nicotine-induced analgesia could make smoking more rewarding and harder to give up.
*Moderation analyses further revealed that acute analgesic effects may be achieved regardless of nicotine delivery method, current smoking status, pain induction modality, study design, or control condition, and that such effects may be more robust among men than women.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/pdf/nihms-774195.pdf PDF Version]
**Citation: Ditre JW, Heckman BW, Zale EL, Kosiba JD, Maisto SA. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain. 2016;157(7):1373-1381. doi:10.1097/j.pain.0000000000000572 (viewed Oct 5, 2021)
***Acknowledgement: This research was supported by NIH Grant Nos. R21DA034285 and R21DA038204 awarded to Joseph W. Ditre, NIH Grant Nos. F31DA033058 and T32DA007288 awarded to Bryan W. Heckman, NIH Grant No. F31DA039628 awarded to Emily L. Zale, and NIH Grant No. 2K05 AA16928 awarded to Stephen A. Maisto.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

===2011 [https://journals.lww.com/ejanaesthesiology/Fulltext/2011/08000/Randomised_trial_of_intranasal_nicotine_and.7.aspx Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women]===
*Intraoperative use of intranasal nicotine has a sustained opioid-sparing effect in non-smoking women undergoing gynaecological procedures and is associated with a higher frequency of nausea.
*[https://sci-hub.st/10.1097/EJA.0b013e328344d998 PDF Version]
*Citation: Jankowski, Christopher J.; Weingarten, Toby N.; Martin, David P.; Whalen, Francis X.; Gebhart, John B.; Liedl, Lavonne M.; Danielson, David R.; Nadeau, Ashley M.; Schroeder, Darrell R.; Warner, David O.; Sprung, Juraj Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women, European Journal of Anaesthesiology (EJA): August 2011 - Volume 28 - Issue 8 - p 585-591 doi: 10.1097/EJA.0b013e328344d998
*Acknowledgements: The present work was supported solely by the Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

===2008 [https://journals.lww.com/anesthesia-analgesia/Fulltext/2008/09000/Transdermal_Nicotine_for_Analgesia_After_Radical.48.aspx Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy]===
*The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in postoperative opioid consumption in nonsmoking men undergoing [[Special:MyLanguage/Abbreviations|'''RRP''']] in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
*[https://sci-hub.se/10.1213/ane.0b013e31816f2616# PDF Version]
*Citation: Habib, Ashraf S., MBBCh, MSc, FRCA*; White, William D., MPH*; El Gasim, Magdi A., MD*; Saleh, Gamal, MD*; Polascik, Thomas J., MD†; Moul, Judd W., MD†; Gan, Tong J., MB, FRCA* Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy, Anesthesia & Analgesia: September 2008 - Volume 107 - Issue 3 - p 999-1004 doi: 10.1213/ane.0b013e31816f2616

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12131122/ Isoflurane hyperalgesia is modulated by nicotinic inhibition]===
*Animal study
*Female mice had significant [https://en.wikipedia.org/wiki/Hyperalgesia hyperalgesia] from [https://en.wikipedia.org/wiki/Isoflurane isoflurane]. Nicotine administration prevented isoflurane-induced hyperalgesia without altering the antinociception produced by higher isoflurane concentrations.
**Citation: Flood P, Sonner JM, Gong D, Coates KM. Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology. 2002 Jul;97(1):192-8. doi: 10.1097/00000542-200207000-00027. PMID: 12131122.
***Acknowledgement: 1P01GM47818/GM/NIGMS NIH HHS/United States, K08GM00695/GM/NIGMS NIH HHS/United States
 

='''Parkinson Disease'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/40465192/ Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease]===
*"In conclusion, these findings suggest potential therapeutic mechanisms of the identified constituents in PD and may provide a basis for future preclinical and clinical studies to further explore their neuroprotective effects."
**Citation: Tusar MTT, Munna MMR, Ahmed MH, Rahman MM, Fatema K, Islam KM, Ali MS. Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease. Cell Biochem Biophys. 2025 Jun 4. doi: 10.1007/s12013-025-01791-6. Epub ahead of print. PMID: 40465192.
***The authors declare no competing interests. (No funding information provided on the version viewed at the link above.)

===2024 [https://www.sciencedirect.com/science/article/abs/pii/S0967586824003849 The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial]===
*The results of our study indicated that nicotine consumption in an isocaloric diet, while preventing a decrease in anthropometric indices, leads to improvements in motor indices and a reduction in alpha-synuclein levels. Additional and larger controlled trials are required to validate these findings.
**Citation: Lorvand Amiri H, Hassan Javanbakht M, Mohammad Baghbanian S, Parsaeian M. The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial. J Clin Neurosci. 2024 Sep 30;129:110845. doi: 10.1016/j.jocn.2024.110845. Epub ahead of print. PMID: 39353253.
***Acknowledgement: This work was supported by the Tehran University of Medical Sciences. (Project No. 53161).

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38430248/ Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease] ===
*Animal study (worms with humanised neurons)
*This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction.
*At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS.
*We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.
*''Note: highly technical brain biochemistry, appears to be important however (ed.)'' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586504/ Paper on the UPS and it's purpose] for info.
**Citation: Ullah I, Uddin S, Zhao L, Wang X, Li H. Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease. Exp Brain Res. 2024 Apr;242(4):971-986. doi: 10.1007/s00221-023-06765-9. Epub 2024 Mar 2. PMID: 38430248.
***Acknowledgement: This study was supported by the Special International Cooperation Project of the Ministry of Science and Technology (2012DFA30480); National Natural Science Foundation of China (No. 81403145); Natural Science Foundation of Gansu Province (No. 20JR10RA602); Fundamental Research Funds for the Central Universities of China (lzujbky—2017-206, lzujbky-2018-136); Science and Technology Cooperation Program of Gansu Academy of Sciences (grant number 2019HZ-02); Program of Lanzhou Science and Technology Foundation (Grant number 2010-1-154). Major science and technology project of Gansu province (23ZDFA013), Natural Science Foundation of Gansu province (20JR10RA602).

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnagi.2023.1223310/full Changes in smoking, alcohol consumption, and the risk of Parkinson’s disease] ===
*A total of 3,931,741 patients were included.
*Compared to the sustained non-smokers, sustained light smokers, sustained moderate smokers, and sustained heavy smokers had a lower risk of PD.
*Compared to those who sustained non-drinking, sustained light drinkers, sustained moderate drinkers, and sustained heavy drinkers showed decreased risk of PD.
*Among non-drinkers, those who started drinking to a light level were at decreased risk of PD. Among non-smoking and non-drinking participants, those who initiated smoking only, drinking only, and both smoking and drinking showed decreased risk of PD.
*Smoking is associated with decreased risk of PD with a dose–response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.
**Citation: Jung SY, Chun S, Cho EB, Han K, Yoo J, Yeo Y, Yoo JE, Jeong SM, Min JH, Shin DW. Changes in smoking, alcohol consumption, and the risk of Parkinson's disease. Front Aging Neurosci. 2023 Sep 13;15:1223310. doi: 10.3389/fnagi.2023.1223310. PMID: 37771519; PMCID: PMC10525683.
***Acknowledgement: J-HM received a grant from the National Research Foundation of Korea and SMC Research and Development Grant. J-HM has lectured, consulted, and received Honoria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Sanofi Genzyme, Teva-Handok, UCB, Samsung Bioepis, Mitsubishi Tanabe Pharma, and Roche.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36817162/ Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.] ===
*Animal Study
*Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo.
*In summary, Nic pretreatment ameliorates MPTP-induced dyskinesia and anxiety-like behavior in mice with PD. Nic was found to alleviate neuroapoptosis by improving nigrostriatal dopaminergic damage, reducing the accumulation of pathological p-α-syn, and inhibiting microglia activation and pro-inflammatory factor expression in the substantia nigra and striatal regions of mice brain under MPTP stimulation. These neuroprotective effects of Nic may be achieved by modulating the JNK and ERK signaling pathways in the nigrostriatal system, which was further confirmed by the pretreatment of 5-MOP to decline the brain metabolic activity of Nic.
**Citation: Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. PMID: 36817162; PMCID: PMC9932206.
***Acknowledgement: This study received funding from the National Science Foundation of China (Grant No. 32072344, 82101506, 32272455), the Scientific and Technological Project of Henan Province of China (Grant No. 182102310157) and the Scientific and Technological Project of China Tobacco Jiangsu Industrial Co., Ltd. (No. H202002). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Authors JX, RJ, and ZG were employed by China Tobacco Jiangsu Industrial Co., Ltd.

===2023: [https://jamanetwork.com/journals/jamaneurology/article-abstract/2805037 Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune]===
*“Parkinson disease risk was substantially lower among Black veterans and EVER-SMOKERS (OR 0.49, 95% CI: 0.40-0.61).
**Citation: Goldman SM, Weaver FM, Stroupe KT, Cao L, Gonzalez B, Colletta K, Brown EG, Tanner CM. Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune. JAMA Neurol. 2023 Jul 1;80(7):673-681. doi: 10.1001/jamaneurol.2023.1168. PMID: 37184848; PMCID: PMC10186205.
***Acknowledgement: This research was supported by clinical science research and development merit award I01 CX002040-01 from the US Department of Veterans Affairs. Support for Veterans Administration (VA)/Centers for Medicare & Medicaid Services data was from the US Department of Veterans Affairs, VA Health Services Research and Development Service, and project numbers SDR 02-237 and 98-004 from the VA Information Resource Center. Dr Weaver reported receiving grants from the Edward Hines, Jr VA Hospital during the conduct of the study and outside the submitted work. Dr Brown reported receiving grants from the Michael J. Fox Foundation and the National Institute on Aging and personal fees from Gateway Consulting, LLC, outside the submitted work. Dr Tanner reported receiving personal fees from Lundbeck Pharma, CNS Ratings, Adamas, Cadent, and Evidera; serving on advisory boards for Kyowa Kirin, Acorda, Australia Parkinson’s Mission; serving on a clinical trial steering committee for Jazz Pharmaceuticals/Cavion; and receiving grants from the National Institutes of Health, Biogen Idec, Parkinson Foundation, Michael J. Fox Foundation, Department of Defense Parkinson’s Research Program, Roche, Genentech, BioElectron, and Gateway Institute for Brain Research, LLC, outside the submitted work. No other disclosures were reported.

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602090/ Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-induced Toxicities in Cell Culture]===
*Preprint, not peer-reviewed.
*In summary, our results not only support neuroprotective effects of nicotine and butyrate in countering Fe and Mn toxicities but indicate a synergistic protection by combination of the two. Moreover, distinct mechanisms of action for each metal, i.e., nicotinic receptor for nicotine and FA3R for butyrate are indicated. Further exploitation of mechanisms of action of butyrate and nicotine may provide novel targets for metal toxicities and/or amelioration of neurodegenerative diseases.
**Citation: Tizabi Y, Getachew B, Aschner M. Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases. Res Sq [Preprint]. 2023 Oct 5:rs.3.rs-3389904. doi: 10.21203/rs.3.rs-3389904/v1. Update in: Neurotox Res. 2023 Dec 14;42(1):3. doi: 10.1007/s12640-023-00682-z. PMID: 37886507; PMCID: PMC10602090.
***Acknowledgement: Supported in part by: NIH/NIAAA R03 AA022479 and NIH/NIGMS (2 SO6 GM08016‐39) (YT), and NIEHS R01ES10563 and R01ES07331 (MA).

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36857384/ Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment.] ===
*Insect study
*We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.
**Citation: Carvajal-Oliveros A, Dominguez-Baleón C, Sánchez-Díaz I, Zambrano-Tipan D, Hernández-Vargas R, Campusano JM, Narváez-Padilla V, Reynaud E. Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment. PLoS One. 2023 Mar 1;18(3):e0282348. doi: 10.1371/journal.pone.0282348. PMID: 36857384; PMCID: PMC9977059.
***Acknowledgement: This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 255478 and by Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (DGAPA-PAPIIT) grant number IN206517) ER was the recipient of the grants. AC received fellowships (446128) from CONACYT, PAEP-UNAM and Alianza del Pacífico- AGCID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

===2021 [https://www.nature.com/articles/s41598-021-88910-4 Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels]===
*Insect study
*In conclusion our data show that the PD model by expression of Sph-1 in dopaminergic neurons provides a good opportunity to study the early prodromal stages of PD, while also the late onset symptoms such as neurodegeneration and motor impairment in aged animals. On the other hand, working on this animal model has allowed us to advance on the therapeutic effects of nicotine treatment over several PD-linked features. The protective effect of nicotine appears to be specific for the genotype predisposed to develop a parkinsonian phenotype and provide a hint on the idea that nicotine treatment even in later stages of the disease could be beneficial to patients. Our findings provide new ideas that contribute to a better understanding on the mechanisms underlying the positive effects of nicotine in PD.
**Citation: Carvajal-Oliveros, A., Domínguez-Baleón, C., Zárate, R.V. et al. Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Sci Rep 11, 9579 (2021). https://doi.org/10.1038/s41598-021-88910-4
***Acknowledgement: This work was supported by the CONACyT (Grant Number 255478) and by DGAPA-PAPIIT (Grant Number IN206517).

=== 2020: [https://n.neurology.org/content/94/20/e2132 Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors] ===
*In contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.
**Citation: Mappin-Kasirer B, Pan H, Lewington S, Kizza J, Gray R, Clarke R, Peto R. Tobacco smoking and the risk of Parkinson disease: A 65-year follow-up of 30,000 male British doctors. Neurology. 2020 May 19;94(20):e2132-e2138. doi: 10.1212/WNL.0000000000009437. Epub 2020 May 5. PMID: 32371450; PMCID: PMC7526668.

===2020 [https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqaa186/5876214?redirectedFrom=fulltext Dietary nicotine intake and risk of Parkinson disease: a prospective study]===
*At 26 year follow-up, women with greater dietary nicotine intake had a lower risk of [[Special:MyLanguage/Abbreviations|'''Parkinson Disease (PD)''']] than those with lower intake. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea.
*[https://sci-hub.st/10.1093/ajcn/nqaa186 PDF Version]
**Citation: Chaoran Ma, Samantha Molsberry, Yanping Li, Michael Schwarzschild, Alberto Ascherio, Xiang Gao, Dietary nicotine intake and risk of Parkinson disease: a prospective study, The American Journal of Clinical Nutrition, Volume 112, Issue 4, October 2020, Pages 1080–1087, doi: 10.1093/ajcn/nqaa186
***Acknowledgements: Supported by National Institute of Neurological Disorders and Stroke at the NIH grant 1R03NS093245-01A1 (to XG). The Nurses’ Health Study is supported by the NIH through grant UM1 CA186107. The Health Professionals Follow-up Study cohort is supported by the NIH through grant U01 CA167552.

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2018 [https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0625-y Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6]===
*Animal study
*The reduced prevalence of Parkinson’s disease in tobacco users is a fascinating phenomenon that is not understood. This study suggests a mechanistic explanation for how tobacco users are protected from Parkinson’s and how the tobacco component nicotine confers neuroprotection; more specifically, nicotine suppresses SIRT6 which confers resistance to neuron and cell death. Few effective treatments exist that prevent neuron death for those suffering from Parkinson’s and other neurodegenerative disorders. The identification of SIRT6 as potentially pathogenic and as a therapeutic target for suppression opens a novel line of research for the treatment of neurodegeneration.
**Citation: Nicholatos, J.W., Francisco, A.B., Bender, C.A. et al. Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6. acta neuropathol commun 6, 120 (2018). https://doi.org/10.1186/s40478-018-0625-y
***Acknowledgement: S.L. and J.W.N. were in part supported by a grant from American Federation for Aging Research (AFAR, grant # 2015–030). S.L. received seed grant funding from the Cornell University Center for Vertebrate Genomics. J.W.N. was supported by a Glenn/AFAR Scholarship for Research in the Biology of Aging.

===2017 [https://academic.oup.com/ije/article/46/3/872/2656164 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Non-smoking men who used snus had a 60% lower risk of Parkinson’s disease compared with never snus users.
**Citation: Yang F, Pedersen NL, Ye W, Liu Z, Norberg M, Forsgren L, Trolle Lagerros Y, Bellocco R, Alfredsson L, Knutsson A, Jansson JH, Wennberg P, Galanti MR, Lager ACJ, Araghi M, Lundberg M, Magnusson C, Wirdefeldt K. Moist smokeless tobacco (Snus) use and risk of Parkinson's disease. Int J Epidemiol. 2017 Jun 1;46(3):872-880. doi: 10.1093/ije/dyw294. PMID: 27940486.
***Acknowledgement: This work was supported by the Swedish Research Council (grant number 521-2013-2488 to N.L.P.) and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (Y.T.L.).

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Author/Acknowledgements: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/ Nicotinic receptors as CNS targets for Parkinson’s disease]===
*Human and animal references
*Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/pdf/nihms32016.pdf PDF Version]
**Citation: Quik M, Bordia T, O'Leary K. Nicotinic receptors as CNS targets for Parkinson's disease. Biochem Pharmacol. 2007 Oct 15;74(8):1224-34. doi: 10.1016/j.bcp.2007.06.015. Epub 2007 Jun 17. PMID: 17631864; PMCID: PMC2046219.
***Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Parkinson's Disease''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against '''Parkinson's Disease''' (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Pemphigus Vulgaris'''=

===2001: [https://pubmed.ncbi.nlm.nih.gov/11737449/ Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire]===
*The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked.
*The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system.
**Citation: Brenner S, Tur E, Shapiro J, Ruocco V, D'Avino M, Ruocco E, Tsankov N, Vassileva S, Drenovska K, Brezoev P, Barnadas MA, Gonzalez MJ, Anhalt G, Nousari H, Ramos-e-Silva M, Pinto KT, Miranda MF. Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire. Int J Dermatol. 2001 Sep;40(9):562-9. doi: 10.1046/j.1365-4362.2001.01266.x. Erratum in: Int J Dermatol. 2003 Sep;42(9):760. Silva MR [corrected to Ramos-e-Silva M]. PMID: 11737449.

===2000: [https://jamanetwork.com/journals/jamadermatology/fullarticle/189739 A Case of Pemphigus Vulgaris Improved by Cigarette Smoking]===
*The patient reported an inverse relationship between smoking and pemphigus flares. He observed a worsening of the pemphigus when he stopped smoking. Nicotine patches were prescribed, but he began smoking cigarettes again instead. On average, he smokes 15 cigarettes per day. One week after he began smoking again, his pemphigus rapidly started to clear.
**Citation: Mehta JN, Martin AG. A case of pemphigus vulgaris improved by cigarette smoking. Arch Dermatol. 2000 Jan;136(1):15-7. doi: 10.1001/archderm.136.1.15. PMID: 10632179.
 

='''Pregnancy'''=
==Preeclampsia==

===2024: [https://www.sciencedirect.com/science/article/abs/pii/S0303720724003022 Nicotine increases hepatocyte transthyretin turnover: a possible mechanism for the protective effect of smoking on preeclampsia?]===
*Nicotine exposure increases hepatocyte synthesis, secretion and uptake of transthyretin as well as cell uptake of soluble endoglin. Nicotine may protect against preeclampsia by increasing serum TTR which can bind soluble endoglin and remove it from the circulation. Further research is required to better understand the role of transthyretin and nicotine in mitigating preeclampsia.
**Citation: Young M, McLeod DSA, Richard K. Nicotine increases hepatocyte transthyretin turnover: A possible mechanism for the protective effect of smoking on preeclampsia? Mol Cell Endocrinol. 2025 Feb 1;597:112446. doi: 10.1016/j.mce.2024.112446. Epub 2024 Dec 24. PMID: 39725350.
***Acknowledgement: This study was funded by the Science Education and Research Committee, Pathology Queensland.
 

='''Psoriasis'''=

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.
 

='''Pyoderma Gangrenosum'''=

===2004 [https://pubmed.ncbi.nlm.nih.gov/15204166/ Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream]===
*Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.
*[https://scihubtw.tw/10.1080/09546630310019364 PDF Version]
**Citations:Patel GK, Rhodes JR, Evans B, Holt PJ. Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream. J Dermatolog Treat. 2004 Apr;15(2):122-5. doi: 10.1080/09546630310019364. PMID: 15204166.

===1998 [https://jamanetwork.com/journals/jamadermatology/fullarticle/189304?fbclid=IwAR33gpEktRMf2Q0v5Btl9C5E8gmXw-ZP8_gDFt6sebxUBpXE_WfVt-o-mSw Nicotine for Pyoderma Gangrenosum]===
*Herein we describe a patient with pyoderma gangrenosum who responded twice to topical nicotine within 4 weeks and 3 months, respectively, without any adverse effects.
*[https://scholar.google.com/scholar_url?url=https://jamanetwork.com/journals/jamadermatology/articlepdf/189304/dce8005.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=Z2aqX4SnOc2rywTPj5aYDw&scisig=AAGBfm1pz6ffl3a23G__I3APgBLpY6Cofw PDF Version]
**Citation: Wolf R, Ruocco V. Nicotine for Pyoderma Gangrenosum. Arch Dermatol. 1998;134(9):1071–1072. doi:10.1001/archderm.134.9.1071

===1995 [https://pubmed.ncbi.nlm.nih.gov/8537562/ Successful treatment of pyoderma gangrenosum with nicotine chewing gum]===
*We used nicotine chewing gum for the treatment of pyoderma gangrenosum with remarkable results. We strongly suggest that nicotine chewing gum may not only be beneficial in treating pyoderma gangrenosum but may also be useful in treating other skin disorders with prominent neutrophilic infiltrations such as Behcet's disease, Sweet disease, allergic vasculitis, and recurrent oral aphthae, the last of which is known to respond to smoking.
*[https://sci-hub.st/10.1111/j.1346-8138.1995.tb03904.x PDF Version]
**Citation: Kanekura T, Kanzaki T. Successful treatment of pyoderma gangrenosum with nicotine chewing gum. J Dermatol. 1995 Sep;22(9):704-5. doi: 10.1111/j.1346-8138.1995.tb03904.x. PMID: 8537562.
 

='''Rett syndrome'''=

===2016: [https://www.nature.com/articles/cr201648 Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus]===
*Animal Study
*In addition, application of PNU282987 or nicotine rescued impaired social interaction and anxiolytic behaviors in Chat-Mecp2−/y mice.
*Nicotine appears to be the primary agent in cigarettes that can target all nAChRs, including α7 nAChRs. Application of nicotine also rescued the behavioral phenotypes of Chat-Mecp2−/y mice. Long-term delivery of nicotine in the hippocampus also improved social memory in WT mice...Of particular importance, intracerebral infusion of PNU282987 or nicotine rescued the behavioral defects in Chat-Mecp2−/y mice. These findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.
**Citation: Zhang Y, Cao SX, Sun P, He HY, Yang CH, Chen XJ, Shen CJ, Wang XD, Chen Z, Berg DK, Duan S, Li XM. Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus. Cell Res. 2016 Jun;26(6):728-42. doi: 10.1038/cr.2016.48. Epub 2016 Apr 22. PMID: 27103432; PMCID: PMC4897179.
***Acknowledgement: This work was supported by the National Natural Science Foundation of China for Distinguished Young Scientists (81225007), Key Project of the National Natural Science Foundation of China (31430034), Major Research Plan of the National Natural Science Foundation of China (91432306), Funds for Creative Research Groups of China (81221003), Program for Changjiang Scholars and Innovative Research Team in University, and Fundamental Research Funds for the Central Universities. This work was also sponsored by the Zhejiang Province Program for Cultivation of High-level Health Talents.
 

='''Sarcoidosis'''=

===2021 [https://journal.chestnet.org/article/S0012-3692(21)01282-4/fulltext Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis]===
===2021 [https://journal.chestnet.org/article/S0012-3692(21)00962-4/fulltext A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis]===
*Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC.
**Citation: A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis, Crouser, Elliott D. et al. CHEST, Volume 160, Issue 4, 1340 - 1349

===2013 [https://journal.chestnet.org/article/S0012-3692(13)60095-1/fulltext Nicotine Treatment Improves Toll-Like Receptor 2 and Toll-Like Receptor 9 Responsiveness in Active Pulmonary Sarcoidosis]===
*The immune phenotype of patients with symptomatic [[wikipedia:Sarcoidosis|'''sarcoidosis''']] treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
*[https://www.researchgate.net/profile/Mark_Julian/publication/230645268_Nicotine_Treatment_Improves_TLR2_and_TLR9_Responsiveness_in_Active_Pulmonary_Sarcoidosis/links/556ca4af08aeab77722318be/Nicotine-Treatment-Improves-TLR2-and-TLR9-Responsiveness-in-Active-Pulmonary-Sarcoidosis.pdf PDF Version]
**Citation: Mark W. Julian, MS; Guohong Shao, MD; Larry S. Schlesinger, MD; Qin Huang, MD; David G. Cosmar, BA; Nitin Y. Bhatt, MD; Daniel A. Culver, MD, FCCP; Robert P. Baughman, MD, FCCP; Karen L. Wood, MD, FCCP; and Elliott D. Crouser, MD - ORIGINAL RESEARCH DIFFUSE LUNG DISEASE| VOLUME 143, ISSUE 2, P461-470, FEBRUARY 01, 2013, DOI 10.1378/chest.12-0383
***Acknowledgements: This work was supported by the American Thoracic Society and the Foundation for Sarcoidosis Research. © 2013 American College of Chest Physicians

===1988:[https://thorax.bmj.com/content/43/7/516.abstract Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.]===
*These finding support the possibility that smokers, particularly those with a prominent accumulation of alveolar macrophages in the lower respiratory tract, may be less likely to develop sarcoidosis.
**Citation: Valeyre D, Soler P, Clerici C, et alSmoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.Thorax 1988;43:516-524.
 

='''Seizures / Epilepsy'''=
*See also:
**Video: News 5: [https://www.youtube.com/watch?v=Ztvf45coKZk Nicotine Stops Seizures]

===2024 [https://www.neurology.org/doi/10.1212/WNL.0000000000209790/ Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch]===
*"Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep."
*"Our case highlights that there may be mechanisms by which nicotine assists with seizure cessation in specific populations of individuals with SHE."
**Citation: Nam S, Von Stein EL, Meador KJ, Levy RJ, Gallentine W, Li Y. Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch. Neurology. 2024 Oct 8;103(7):e209790. doi: 10.1212/WNL.0000000000209790. Epub 2024 Sep 9. PMID: 39250747; PMCID: PMC11385953.

===2021 [https://pubmed.ncbi.nlm.nih.gov/34763266/ Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients]===
*This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.
**Citation: Brodtkorb E, Myren-Svelstad S, Knudsen-Baas KM, Nakken KO, Spigset O. Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients. Epilepsy Res. 2021 Oct 25;178:106792. doi: 10.1016/j.eplepsyres.2021.106792. Epub ahead of print. PMID: 34763266.

===2021 [https://www.pedneur.com/article/S0887-8994(21)00147-8/fulltext Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy]===
*Nevertheless, the two siblings reported here add to the small number of pediatric case reports regarding the successful use of nicotine patches in ADSHE.
*Journal Pre-Proof [https://www.pedneur.com/action/showPdf?pii=S0887-8994%2821%2900147-8 PDF Version]
**Citation: Nguyen SM, Deering L, Nelson GT, McDaniel SS, Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy, Pediatric Neurology (2021), doi:10.1016/j.pediatrneurol.2021.07.006.

===2021 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable."
*"Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031.

===2020 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction."
*"Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031

===2020 [https://pubmed.ncbi.nlm.nih.gov/32097883/ Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy]===
*"Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions."
**Citation: Lossius K, de Saint Martin A, Myren-Svelstad S, Bjørnvold M, Minken G, Seegmuller C, Valenti Hirsch MP, Chelly J, Steinlein O, Picard F, Brodtkorb E. Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy Behav. 2020 Apr;105:106944. doi: 10.1016/j.yebeh.2020.106944. Epub 2020 Feb 22. PMID: 32097883.

===2018 [https://www.dovepress.com/sleep-related-hypermotor-epilepsy-prevalence-impact-and-management-str-peer-reviewed-fulltext-article-NSS Sleep-related hypermotor epilepsy: prevalence, impact and management strategies]===
*"Seizure frequency improved in a single patient with refractory ADSHE after nicotine transdermal patches treatment.(108) The favorable effect of nicotine on seizure frequency was also described in 9 of 22 patients from two European ADSHE families carrying CHRNA4 mutations.(109) Considering the role of the cholinergic system in arousal regulatory processes, these observations suggested a possible link between nicotine defect, alteration of arousal regulation and seizures in SHE/ADSHE patients. However, despite the reported positive effect of nicotine in reducing seizure frequency, a case–control family study, did not find a higher tendency to smoke tobacco in SHE patients and their relatives compared with the control cases.(110)
**Citation: Menghi V, Bisulli F, Tinuper P, Nobili L. Sleep-related hypermotor epilepsy: prevalence, impact and management strategies. Nat Sci Sleep. 2018 Oct 10;10:317-326. doi: 10.2147/NSS.S152624. PMID: 30349413; PMCID: PMC6186898.

===2015 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433466/ Pearls & Oy-sters: A case of refractory nocturnal seizures]===
*"Due to frequent seizures, there was a paucity of slow-wave sleep and complete absence of REM sleep. On the second day of her hospital admission, a 7-mg nicotine patch was applied about 2–3 hours before bedtime. There was almost complete resolution of clinical and electrical events. The duration of slow-wave sleep increased and REM sleep was recorded. The next morning, the patient felt refreshed and less anxious."
**Citation: Pavlakis PP, Douglass LM. Pearls & Oysters: A case of refractory nocturnal seizures: Putting out fires without smoke. Neurology. 2015 May 5;84(18):e134-6. doi: 10.1212/WNL.0000000000001539. PMID: 25941204; PMCID: PMC4433466.

===2012 [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2012.03715.x Resolution of epileptic encephalopathy following treatment with transdermal nicotine]===
*We report resolution of an epileptic encephalopathy by administration of transdermal nicotine patches in an adolescent with severe nonlesional refractory frontal lobe epilepsy. The 18.5‐year‐old female patient had refractory epilepsy from the age of 11. Recurrent electroencephalography (EEG) recordings showed mostly generalized activity, albeit with right frontal predominance. Almost all antiepileptic medications failed to provide benefit. She developed an encephalopathic state with cognitive decline. The nonlesional frontal lobe epilepsy and a family history of a cousin with nocturnal epilepsy with frontal origin suggested genetic etiology. Transdermal nicotine patches brought complete resolution of the seizures, normalization of the EEG, and a significant improvement in her thinking process and speech organization. Sequencing of the CHRNB2 and CHRNA4 genes did not detect a mutation. Transdermal nicotine patches should be considered in severe pharmacoresistant frontal lobe epilepsy.
*[https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03715.x PDF Version]
**Citation: Zerem, A., Nishri, D., Yosef, Y., Blumkin, L., Lev, D., Leshinsky‐Silver, E., Kivity, S. and Lerman‐Sagie, T. (2013), Resolution of epileptic encephalopathy following treatment with transdermal nicotine. Epilepsia, 54: e13-e15. doi: 10.1111/j.1528-1167.2012.03715.x

===2006 [https://pubmed.ncbi.nlm.nih.gov/16931165/ Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy]===
*"This study indicates that nicotine consumption is an environmental factor that, in many patients with ADNFLE, may influence susceptibility to seizures. A detailed account of tobacco habits should be part of the history. Transdermal nicotine should be considered in pharmacoresistant cases."
*[https://sci-hub.se/10.1016/j.yebeh.2006.07.008 PDF Full study]
**Citation: Brodtkorb E, Picard F. Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Behav. 2006 Nov;9(3):515-20. doi: 10.1016/j.yebeh.2006.07.008. Epub 2006 Aug 22. PMID: 16931165.

===2003 [https://onlinelibrary.wiley.com/doi/full/10.1046/j.1528-1157.2003.58102.x-i1?sid=nlm%3Apubmed Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study]===
*In this individual with refractory [[Special:MyLanguage/Abbreviations|'''ADNFLE''']], nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
*[https://sci-hub.st/https://doi.org/10.1046/j.1528-1157.2003.58102.x-i1 PDF Version]
**Citation: Willoughby, J.O., Pope, K.J. and Eaton, V. (2003), Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study. Epilepsia, 44: 1238-1240. doi: 10.1046/j.1528-1157.2003.58102.x-i1
 

='''Sepsis/Septic/endotoxemia/infection'''=
===2024 [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2014 [https://academic.oup.com/jid/article/209/10/1668/855517#78932729 Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation]===
*Animal study
*In conclusion, stimulation of α7nAChR by nicotine improves mortality rates and MODS during sepsis. This protective effect of nicotine can be associated with the inhibition of TLR4 overexpression through the PI3K/Akt signaling pathway. Although the therapeutic potential of nicotine is still limited by its nonspecific effects, this study may provide an impetus for further development of therapeutic strategies for modifying the cholinergic antiinflammatory pathway in the treatment of various inflammatory diseases.
**Citation: Kim TH, Kim SJ, Lee SM. Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation. J Infect Dis. 2014 May 15;209(10):1668-77. doi: 10.1093/infdis/jit669. Epub 2013 Dec 1. Erratum in: J Infect Dis. 2015 Mar 1;211(5):851. doi: 10.1093/infdis/jiu824. PMID: 24298024.
***Acknowledgement: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (NRF-2013R1A1A3008145).

===2011 [https://pubmed.ncbi.nlm.nih.gov/20805763/ Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide]===
*Animal Study
*The results suggested that both carbachol and nicotine play a role in the anti-inflammatory process and organ function protection through the α7 subunit of nicotinic cholinergic receptor.
*[https://sci-hub.st/10.1097/TA.0b013e3181e9732d PDF Full Paper]
**Citation: Zhou G, Hu S, Lv Y, Song Q, Zou X, Sheng Z. Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide. J Trauma. 2011 Jul;71(1):157-62. doi: 10.1097/TA.0b013e3181e9732d. PMID: 20805763.
***Acknowledgement: From the Laboratory of Shock and Organ Dysfunction (G.Z., S.H., Y.L., Q.S., X.Z., Z.S.), Burn Institute, the First Hospital Affiliated to the People’s Liberation Army General Hospital, Beijing, China.

===2005 [https://academic.oup.com/jid/article/191/12/2138/842542 The Cholinergic Anti-Inflammatory Pathway Regulates the Host Response during Septic Peritonitis]===
*Animal Study
*"Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired."
**Citation: van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis. 2005 Jun 15;191(12):2138-48. doi: 10.1086/430323. Epub 2005 May 10. PMID: 15898001.
***Acknowledgement: Financial support: Academic Medical Center, Amsterdam, The Netherlands. Potential conflicts of interest: K.J.T. is cofounder of Critical Therapeutics Inc., a pharmaceutical company developing potential future treatment modalities based on the cholinergic anti-inflammatory pathway.

='''Sleep'''=

==Apnea==

===1991: [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against sleep apnea (other diseases / issues mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1985: [https://pubmed.ncbi.nlm.nih.gov/3965253/ Nicotine: a different approach to treatment of obstructive sleep apnea]===
*Reduced upper airway muscle activity may contribute to the occurrence of obstructive apneas during sleep. There is no uniformly successful treatment of these apneas, and it is possible that agents which increase upper airway muscle activity could reduce the occurrence of obstruction during sleep. Nicotine, a known stimulant of breathing, also increases the activity of muscles which dilate the upper airway proportionally more than it does ventilation. Hence, we evaluated the effect of nicotine on apneas during the first two hours of sleep in eight patients with sleep apnea syndrome. It was concluded that nicotine reduces apneas during the early hours of sleep, and this effect may be caused by its stimulating action on upper airway muscles.
*[https://sci-hub.se/10.1378/chest.87.1.11 PDF Version]
**Citation: Gothe B, Strohl KP, Levin S, Cherniack NS. Nicotine: a different approach to treatment of obstructive sleep apnea. Chest. 1985 Jan;87(1):11-7. doi: 10.1378/chest.87.1.11. PMID: 3965253.
***Acknowledgement: None found

==REM==

===2017: [https://onlinelibrary.wiley.com/doi/10.1002/brb3.704 Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus]===
*Animal study
*MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein.
**Citation: Abd Rashid N, Hapidin H, Abdullah H, Ismail Z, Long I. Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus. Brain Behav. 2017; 7:e00704. https://doi.org/10.1002/brb3.704
***Acknowledgement: This study was supported by the Universiti Sains Malaysia (USM) Short-Term Grant Scheme (304/PPSK/61312093), USM Research University grants (RUI) (1001/PPSK/812139) and Fundamental Research Grant Scheme (FRGS) (203/PPSK/6171153).

===2011: [https://onlinelibrary.wiley.com/doi/10.1002/hipo.20806 Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat]===
*Animal Study
*However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.
*[https://www.academia.edu/18461315/Acute_nicotine_treatment_prevents_REM_sleep_deprivation_induced_learning_and_memory_impairment_in_rat PDF Full paper]
**Citation: Aleisa, A.M., Helal, G., Alhaider, I.A., Alzoubi, K.H., Srivareerat, M., Tran, T.T., Al-Rejaie, S.S. and Alkadhi, K.A. (2011), Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat. Hippocampus, 21: 899-909. https://doi.org/10.1002/hipo.20806
***Acknowledgement: None found
 

='''Smoking Cessation / Preventing Relapse'''=
===Resource Doc: [https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO - Myth of the month: Ecigs and snus don’t help smokers quit]===
*Links and conclusions of studies formatted to fit the character limits on Twitter

===[https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]===
*This wiki page shows over 70 studies demonstrating these products help people stop smoking.
 

='''Spinal Cord Injury'''=
===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
*Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
*Acknowledgements: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.
*Key words: spinal cord injury; nicotine; neuronal nicotinic receptors; oxidative stress; inflammatory responses; nitric oxide synthase

= Stroke =

=== 2025: '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf034/8005730?redirectedFrom=fulltext&login=false The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]''' ===

* Animal study (mice)
* These results demonstrate that nicotine treatment could alleviates the IS-compromised integrity of BBB by regulating the Wnt signal pathway through α7 nAChR.
* The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke.
* Qianqian Pang, Xinyang Yan, Zheng Chen, Liang Yun, Jiang Qian, Zeyi Dong, Miao Wang, Wei Deng, Yao Fu, Tao Hai, Zhichao Chen, Xianfang Rong: Nicotine & Tobacco Research, ntaf034, <nowiki>https://doi.org/10.1093/ntr/ntaf034</nowiki>

='''Tobacco Use Disorder'''=

===2023: [https://link.springer.com/article/10.1007/s11606-023-08137-z Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===
*The remarkable decline in cigarette smoking since 1964 has plateaued; approximately 12.5% of Americans still smoke. People who continue to smoke are largely members of marginalized groups, such as people with behavioral health conditions (BHC), encompassing both mental health and substance use disorders.
*Although not a panacea, electronic cigarettes may represent a powerful harm reduction tool amongst subpopulations traditionally left behind in conventional smoking cessation movements. The argument in favor of studies of electronic cigarettes as a smoking cessation, harm reduction intervention in people with BHC is multi-faceted. People with BHC have higher levels of smoking burdens and nicotine addiction compared to the general population, and they quit at lower rates. Unlike NRT, the nicotine delivery from an electronic cigarette mimics the nicotine pharmacokinetics of tobacco cigarettes unaccompanied by high levels of toxicants and carcinogens.22 Thus, electronic cigarettes may be well positioned to satisfy this nicotine addiction, and mitigate the intense nicotine withdrawal symptoms that sabotage many quit attempts. People with BHC want to stop smoking, and indicators suggest that electronic cigarettes would be an acceptable and well-received intervention.
**Citation: Vuong, J.T., Ruedisueli, I., Beaudin, C.S. et al. Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders. J GEN INTERN MED 38, 1970–1974 (2023). https://doi.org/10.1007/s11606-023-08137-z
***Acknowledgement: None stated

='''Tourette's Syndrome'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012 [https://pubmed.ncbi.nlm.nih.gov/22776623/ Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond]===
* The article presents a mini-review of studies on TS and depression over the past 25 years.
* It summarizes the studies on the behavioral biology of the basal ganglia and its neurotransmitters.
* It describes research with TS patients to evaluate the therapeutics of nicotine and mecamylamine.
* [https://sci-hub.se/10.1016/j.physbeh.2012.06.023 PDF Version]
*Citation: Sanberg, P. R., Vindrola-Padros, C., & Shytle, R. D. (2012). Translating laboratory discovery to the clinic: From nicotine and mecamylamine to Tourette’s, depression, and beyond. Physiology & Behavior, 107(5), 801–808. doi:10.1016/j.physbeh.2012.06.023
*Acknowledgement: Paul R. Sanberg and R. Douglas Shytle are inventors on patents related to technology described herein and licensed from the University of South Florida to Targacept, Inc. Because of the historical nature of this article, the authors included a number of self-citations required for a chronological discussion.

===2004 [https://pubmed.ncbi.nlm.nih.gov/15132126/ Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome]===
*In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 hours, but counteracted [https://en.wikipedia.org/wiki/P300_(neuroscience) ERP-P300] signs of diminished attention seen 2 weeks following placebo treatment.
*Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention.
*[https://sci-hub.st/10.1016/j.eurpsy.2003.11.002 PDF Version ]
*Citation: Howson, A. L., Batth, S., Ilivitsky, V., Boisjoli, A., Jaworski, M., Mahoney, C., & Knott, V. J. (2004). Clinical and attentional effects of acute nicotine treatment in Tourette’s syndrome. European Psychiatry, 19(2), 102–112. doi:10.1016/j.eurpsy.2003.11.002
*Acknowledgement: This study was supported with a grant from the Tourette Syndrome Association (USA), and patient recruitment was aided by the Ottawa chapter of the Tourette Syndrome Foundation of Canada.

===2001 [https://pubmed.ncbi.nlm.nih.gov/11681767/ Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study]===
*[[Special:MyLanguage/Abbreviations|'''Transdermal nicotine (TNP)''']] was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder
*[https://www.researchgate.net/profile/Paul_Sanberg/publication/11670769_Transdermal_Nicotine_and_Haloperidol_in_Tourette's_Disorder/links/5be32624299bf1124fc2d86a/Transdermal-Nicotine-and-Haloperidol-in-Tourettes-Disorder.pdf PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Wilkinson BJ, McConville B, Sanberg PR. Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study. J Clin Psychiatry. 2001 Sep;62(9):707-14. doi: 10.4088/jcp.v62n0908. PMID: 11681767.

===1997 [https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994 Nicotine for the treatment of Tourette's syndrome]===
*Within 24 hr of the application of a single 7-mg [[Special:MyLanguage/Abbreviations|'''TNP (nicotine patch)''']], the severity and frequency of tic symptoms is significantly decreased over baseline. This response is rapid, often reaching its maximum in the first 3 hr after application of a single patch. The duration of therapeutic effect of a single 7-mg TNP is variable and may last for about l-2 weeks.
*Application of a 7-mg TNP to children and adolescents with [[Special:MyLanguage/Abbreviations|'''TS''']] appears to be clinically safe, with transient side effects. However, no child under 8 years of age and weighing less than 25 kg was considered for TNP treatment.
*[https://sci-hub.st/https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994?via%3Dihub PDF Version]
*Citation: Paul R. Sanberg, Archie A. Silver, R.Doug Shytle, Mary Katherine Philipp, David W. Cahill, Harold M. Fogelson, Brian J. McConville, Nicotine for the treatment of Tourette's syndrome, Pharmacology & Therapeutics, Volume 74, Issue 1, 1997, Pages 21-25, ISSN 0163-7258, doi.org/10.1016/S0163-7258(96)00199-4.
* Acknowledgements-This review was supported, in part, by grants from the Tourette Syndrome Association, The National Institute of Neurological Disease and Stroke (ROl NS 32067sOlAl) and the Smokeless Tobacco Research Council.
*Keywords: Nicotine; Tourette's syndrome; tics; neuropsychiatric disorders

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Gilles de la Tourette’s syndrome (TS)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

=== 1996 [https://pubmed.ncbi.nlm.nih.gov/8973070/ Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome]===
* Sixteen Tourette's syndrome patients, aged 9 to 15 years, whose symptoms were not controlled with neuroleptics, were followed for various lengths of time after the application of one 7 mg [[Special:MyLanguage/Abbreviations|'''transdermal nicotine patch (TNP)''']] for 24 hours. While there was a broad range in individual response, application of the TNP produced significant reductions in [[Special:MyLanguage/Abbreviations|'''Yale Global Tic Severity Scale (YGTSS)''']] scores relative to baseline, with an average duration of effect lasting between 1 and 2 weeks. Side effects, for the most part, were transient.
*Eleven patients had greater percentage changes after the second TNP than after the first TNP
*[https://sci-hub.st/10.1097/00004583-199612000-00015 PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Sanberg PR. Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1996 Dec;35(12):1631-6. doi: 10.1097/00004583-199612000-00015. PMID: 8973070.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1643197/ The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder]===
*In this study, nicotine markedly potentiated haloperidol effects in treating [[Special:MyLanguage/Abbreviations|'''TD''']], and showed lesser effects on TD when used alone.
*[https://sci-hub.st/10.1016/0006-3223(92)90315-q PDF Version]
* Citation: McConville BJ, Sanberg PR, Fogelson MH, King J, Cirino P, Parker KW, Norman AB. The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder. Biol Psychiatry. 1992 Apr 15;31(8):832-40. doi: 10.1016/0006-3223(92)90315-q. PMID: 1643197.
*Acknowledgements: Supported in part by grants from the Smokeless Tobacco Research Council, Inc., the Tourette Syndrome Association, and Merrell Dow Pharmaceuticals. The authors thank Roger Stuebing, B.S.M.E., M.S.I.E., and Sunny Y. Lu, M.D., Ph.D. for statistical advice and Merrell Dow Pharmaceuticals for supplying both Nicoreue® gum and placebo nicotine gum.

='''Weight Loss / Appetite Control / Metabolism / Obesity'''=

===2024 Article [https://web.archive.org/web/20241204102835/https://tobaccoreporter.com/2024/12/03/slim-chances/ Harm reduction, smoking cessation and weight]====
*"Nicotine influences eating and weight in multiple ways, from hormones to microbiomes to taste perceptions. The bottom line: Nicotine raises the metabolic rate while also depressing appetite."

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
**Citation: Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database of Systematic Reviews 2021, Issue 10. Art. No.: CD006219. DOI: 10.1002/14651858.CD006219.pub4. Accessed 03 July 2025.
***[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/information Acknowledgement]

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.
*Low-grade inflammation is a key feature of obesity and links obesity to insulin resistance, impaired glucose tolerance and even diabetes.
*Overall, these findings suggest that nicotine and specific α7nAChR agonists may be beneficial in the prevention and treatment of obesity-induced inflammation and insulin resistance. However, there is also evidence that heavy smoking affects body fat distribution that is associated with central obesity and insulin resistance. Moreover, smoking appears to aggravate insulin resistance in persons with type 2 diabetes and to impair glycemic control.
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in reduction of body weight
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Suggested additions to this page'''=

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.

===2925: [https://link.springer.com/article/10.1186/s12890-025-04071-4 Modulatory roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats]===

===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===
*[https://sci-hub.st/10.1007/s12640-021-00375-5 PDF Full paper]

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

===[https://www.researchgate.net/publication/325159226_Resolution_of_chronic_rhinitis_to_staphylococcus_aureus_in_a_non-smoker_who_started_to_use_glycerine_based_e-cigarettes_Antibacterial_effects_of_vaping Resolution of chronic rhinitis to staphylococcus aureus in a non-smoker who started to use glycerine based e-cigarettes: Antibacterial effects of vaping?]===

===2019: [https://medium.com/parkinsons-uk/protecting-brain-cells-the-story-of-nicotine-b3b51f5b8259 Protecting brain cells — the story of nicotine]===
*[https://web.archive.org/web/20221021040501/https://www.parkinsons.org.uk/nicotine-good-bad-and-ugly Nicotine - Good, Bad, Ugly]

===2018: [https://pubmed.ncbi.nlm.nih.gov/29770521/ Nicotine-mediated neuroprotection of rat spinal networks against excitotoxicity]===

===2017 [https://www.ncbi.nlm.nih.gov/pubmed/27940486 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
*different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German) 'Cognition: nicotine versus neuropsychiatric disorders' ===

===Dr. Newhouse [http://mindstudy.org/news Mind Study]===

===2010 [https://pubmed.ncbi.nlm.nih.gov/20414766/ Meta-analysis of the acute effects of nicotine and smoking on human performance] and 2012 [https://n.neurology.org/content/78/2/91.short Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*Clinical studies suggest some cognitive improvements as a result of nicotine.

===2021 [https://www.dovepress.com/effectiveness-and-safety-profile-of-alternative-tobacco-and-nicotine-p-peer-reviewed-fulltext-article-JMDH Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review]===

===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].”
https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===

===To do: Go through the references for nicotine related studies===
====2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]====

===1989 [https://www.sciencedirect.com/science/article/abs/pii/002432058990444X?via%3Dihub Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders]===
*Chewing nicotine gum produced striking relief from tics and other symptoms of Tourette syndrome not controlled by neuroleptic treatment alone. It appears that the use of nicotine or cannabinoids may greatly improve the clinical response to neuroleptics in motor disorders.
*[https://sci-hub.st/https://doi.org/10.1016/0024-3205(89)90444-X PDF Version]
*Citation: D.E. Moss, Patricia Z. Manderscheid, S.P. Montgomery, Andrew B. Norman, Paul R. Sanberg, Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders, Life Sciences, Volume 44, Issue 21, 1989, Pages 1521-1525, ISSN 0024-3205, doi.org/10.1016/0024-3205(89)90444-X.
*Acknowledgements: Supported in part by NIMH (RR 08012) and NIDA. Levonantradol and fluphenazine HCL were generous gifts from Pfizer Pharmaceuticals (Groton, Conn.) and E.R. Squibb and Sons (Princeton, N.J.), respectively.

===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

===[https://www.researchgate.net/publication/325159226_Resolution_of_chronic_rhinitis_to_staphylococcus_aureus_in_a_non-smoker_who_started_to_use_glycerine_based_e-cigarettes_Antibacterial_effects_of_vaping Resolution of chronic rhinitis to staphylococcus aureus in a non-smoker who started to use glycerine based e-cigarettes: Antibacterial effects of vaping?]===

===2019: [https://medium.com/parkinsons-uk/protecting-brain-cells-the-story-of-nicotine-b3b51f5b8259 Protecting brain cells — the story of nicotine]===
*[https://web.archive.org/web/20221021040501/https://www.parkinsons.org.uk/nicotine-good-bad-and-ugly Nicotine - Good, Bad, Ugly]

===2017 [https://www.ncbi.nlm.nih.gov/pubmed/27940486 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
*different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German) 'Cognition: nicotine versus neuropsychiatric disorders' ===

===Dr. Newhouse [http://mindstudy.org/news Mind Study]===

===2010 [https://pubmed.ncbi.nlm.nih.gov/20414766/ Meta-analysis of the acute effects of nicotine and smoking on human performance] and 2012 [https://n.neurology.org/content/78/2/91.short Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*Clinical studies suggest some cognitive improvements as a result of nicotine.

===2021 [https://www.dovepress.com/effectiveness-and-safety-profile-of-alternative-tobacco-and-nicotine-p-peer-reviewed-fulltext-article-JMDH Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review]===

===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].”
https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===

===To do: Go through the references for nicotine related studies===
====2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]====

[[Category:Studies, Surveys, and Papers]]
[[Category:THR product]]
[[Category:THR Stories]]

Nicotine therapeutic benefits

2026-04-04T16:09:58Z

Skip: /* 2021: Interventions for preventing weight gain after smoking cessation */

<big>'''''Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that fewer people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine. Some of these studies show a potential benefit, not proof of a benefit. Some of the studies are animal studies, not human studies.'''''</big>
 
 
[[File:Nic Ther Ben.png|alt=Nicotine Therapeutic benefits banner|center]]
 

 

<big>'''Note: Some topics are subgroups under the main topic of "Mental Health." '''</big>
 

='''Acne'''=

===2010 [https://ijphjournal.it/article/view/5708 Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies]===
*Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis.
*Our meta-analysis underlines that there is no evidence to support an association between smoking habits and acne, although in three of the good quality papers a significant protection in the current smoker was found. It necessary to be cautious in declaring that smoking may provide a protective effect in the pathogenesis of acne because the analysis was based on only a small number of studies.

===2006 [https://www.sciencedirect.com/science/article/pii/S0022202X15330153 Severe Acne Vulgaris and Tobacco Smoking in Young Men]===
*It is crucial to emphasize that any positive effects found must be traced to specific tobacco components that can be therapeutically used without smoking (e.g., nicotine patches or gums), to avoid any “legitimatizing” of smoking based on its beneficial effects on health.
*Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P=0.0078).
*Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

===1993 [https://academic.oup.com/ced/article-abstract/18/2/100/6629365 Does smoking influence acne?]===
*[https://sci-hub.se/10.1111/j.1365-2230.1993.tb00986.x PDF of full study]
*The findings of this study support the hypothesis that some component of cigarette smoke, possibly nicotine, has an anti‐inflammatory action on acne.
 

='''ADD / ADHD / Attention / Cognition'''=

=== 2025 '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf060/8078909 Nicotine improves working memory via augmenting BDNF levels through α7 nAChR: evidence from clinical and pre-clinical studies]''' ===

* While smoking has been associated with many negative consequences to human health, one possible benefit is that nicotine could improve cognitive functions. Previous studies have suggested that smoking may influence brain-derived neurotrophic factor (BDNF) levels.
* Our research revealed that tobacco product use led to an increase in working memory and human plasma BDNF levels. Furthermore, nicotine was responsible for the elevation in BDNF levels, which showed dose-dependent increases in both serum and the hippocampus, and improved memory performance.
* Animal study (rat)
* ''Yingyan Li, PhD, Xin Li, Yaning Fu, PhD, Wenjun Mou, Zuxin Chen, PhD, Ping Wu, PhD, Fanglin Liu, PhD, Huan Chen, PhD, Hongwei Hou, PhD, Qingyuan Hu, PhD: Nicotine & Tobacco Research'', ntaf060, <nowiki>https://doi.org/10.1093/ntr/ntaf060</nowiki>

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.845646/full Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms]===
*"Our review of evidence supports the finding that individuals with ADHD are at greater vulnerability for both initiation and continuation of smoking (both cigarettes, e-cigarettes)."
*"Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes."
*Taylor, M. R., Carrasco, K., Carrasco, A., & Basu, A. (2022). Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms. Frontiers in Neuroscience, 16, 845646. https://doi.org/10.3389/fnins.2022.845646
*Funds for open access publication fees are contributed by the Faculty of Health, University of Canterbury and University of Canterbury library.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*High rates of smoking are observed among individuals with psychiatric disorders including schizophrenia, bipolar disorder, major depression, attention deficit hyperactivity disorder (ADHD) and comorbid substance use disorders (SUD). Because these psychiatric disorders are associated with various cognitive impairments, including deficits in attention, working memory, and response inhibition functions, the cognitive enhancing effects of nicotine may be especially important determinants of the initation and maintenance of smoking in this comorbid population. Growing evidence suggest that cognitive enhancing effects of nicotine may also contribute to the difficulty in quitting smoking, especially in individuals with psychiatric disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.tandfonline.com/doi/full/10.1080/10826084.2017.1334066 Causal Factors of Increased Smoking in ADHD: A Systematic Review]===
*One of the most striking comorbidities of ADHD is nicotine dependence. Youth diagnosed with ADHD are 2–3 times more likely to smoke than their peers without ADHD, initiate smoking earlier in life and progress more quickly and more frequently to regular use and dependence. Possible explanations for these increased risks are: (a) self-medication of ADHD symptoms with the stimulant nicotine; (b) ADHD symptoms like inattention and hyperactivity/impulsivity predispose for smoking initiation and impede smoking cessation; (c) peer pressure; and/or (d) common genetic or environmental determinants for ADHD and smoking.
*In contrast, the positive relation between ADHD and nicotine dependence is currently best explained by the self-medication hypothesis. This hypothesis has a clear pharmacological rationale and is supported by ample evidence, but awaits confirmation from longitudinal naturalistic studies.
*Citation: Jan van Amsterdam, Bauke van der Velde, Mieke Schulte & Wim van den Brink (2018) Causal Factors of Increased Smoking in ADHD: A Systematic Review, Substance Use & Misuse, 53:3, 432-445, DOI: 10.1080/10826084.2017.1334066

===2014: [https://www.medscape.com/viewarticle/827544_1 Adult Attention-Deficit/Hyperactivity Disorder and Nicotine Use: A Qualitative Study of Patient Perceptions]===
*Participants had different views about the link between cigarette smoking and ADHD. While the majority thought of nicotine as a sort of therapy, viewing smoking as a way to self-medicate symptoms of ADHD, motivations for nicotine use were also related to self-image, desire to belong to a peer-group, and a drive to undermine perceived social norms. Ultimately, these findings can be used by clinicians to improve treatment alliance and collaboration.
*[https://sci-hub.se/10.1186/1471-244x-14-141 Alternative Link]
*Citation: Liebrenz, M., Frei, A., Fisher, C. E., Gamma, A., Buadze, A., & Eich, D. (2014). Adult attention-deficit/hyperactivity disorder and nicotine use: a qualitative study of patient perceptions. BMC Psychiatry, 14(1). doi:10.1186/1471-244x-14-141

===2011 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353150/ Cognitive enhancers for the treatment of ADHD]===
*Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting approximately 8–9% of school-aged children and 4–5% of adults (Froehlich et al., 2007; Kessler et al., 2006; Visser et al., 2007). Although formally the disorder is characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity (APA, 2000), myriad phenotypic features—many of which are related to cognition broadly defined—have been shown to distinguish those with ADHD from those without the disorder.
*Together, these findings have led to the hypothesis that individuals with ADHD may smoke in order to alleviate requisite symptoms of the disorder and further suggest nicotine and/or nicotinic agonists can be used to improve aspects of cognitive function in these patients (McClernon and Kollins, 2008). Some support for this hypothesis has been provided by studies which have shown positive effects of nicotine on ADHD symptoms (Gehricke et al., 2009; Shytle et al., 2002) and cognitive performance (Levin et al., 1996; Potter and Newhouse, 2004) in non-smokers with ADHD. Whereas there are currently no FDA-approved nicotinic agonists to treat ADHD, laboratory and small-scale clinical trials have been conducted in recent years, and novel nicotinic pharmacotherapies are on the horizon.
*Citation: Bidwell LC, McClernon FJ, Kollins SH. Cognitive enhancers for the treatment of ADHD. Pharmacol Biochem Behav. 2011 Aug;99(2):262-74. doi: 10.1016/j.pbb.2011.05.002. Epub 2011 May 10. PMID: 21596055; PMCID: PMC3353150.

===2009 [https://pubmed.ncbi.nlm.nih.gov/20025370/ Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder]===
*Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.
*Citation: Gehricke, J. G., Hong, N., Whalen, C. K., Steinhoff, K., & Wigal, T. L. (2009). Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors, 23(4), 644–655. https://doi.org/10.1037/a0017441

===2009 [https://www.tandfonline.com/doi/abs/10.3109/15622970209150616 A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder]===
*All 10 subjects enrolled (six males, four females; mean age = 10 years, SEM = 0.8) completed the study. As assessed by the 48-item Conners Parent Rating Scale at endpoint and during the trial, there was a significantly greater reduction in ADHD symptoms on “Learning Problems” and “Hyperactivity” subfactors. Nausea, stomach ache, itching under patch and dizziness were the most frequently reported adverse effects associated with transdermal nicotine.
*Citation: R. Douglas Shytle, Archie A. Silver, Berney J. Wilkinson & Paul R. Sanberg (2002) A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder, The World Journal of Biological Psychiatry, 3:3, 150-155, DOI: 10.3109/15622970209150616

===2008 [https://www.sciencedirect.com/science/article/abs/pii/S0091305707003048?via%3Dihub Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to [[Special:MyLanguage/Abbreviations|'''ADHD''']].
*[https://sci-hub.st/https://doi.org/10.1016/j.pbb.2007.09.014 PDF Version]
*Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.
*Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.

===2008 [https://pmc.ncbi.nlm.nih.gov/articles/PMC2446482/ Transdermal Nicotine in Adult ADHD With Depression and Anxiety]===
*"This case report neither rules out the placebo effect, nor does it prove that transdermal nicotine is useful in managing adult ADHD with depression and anxiety. However, it does suggest that the beneficial effect of transdermal nicotine may be attributed to biobehavioral pathways common to chronic nicotine withdrawal and ADHD with depression and anxiety. Nicotine agonists and delivery systems may be new treatments for adult ADHD. Larger well-designed studies are warranted to evaluate the therapeutic potential of nicotine delivery systems in otherwise medically stable adults with ADHD accompanied by depression and anxiety. Further exploration of the nicotinic-cholinergic system may also expand our understanding of the neuropsychiatry underlying ADHD."
*Citation: Cocores JA. Transdermal nicotine in adult ADHD with depression and anxiety. Prim Care Companion J Clin Psychiatry. 2008;10(3):253-4. doi: 10.4088/pcc.v10n0312f. PMID: 18615164; PMCID: PMC2446482.
*Dr. Cocores reports no financial affiliations or other relationships relevant to the subject of this letter.

===2007 [https://www.academia.edu/2412620/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
*The data from diverse studies are generally consistent with the self-medication hypothesis and suggest that individuals with ADHD may smoke to alleviate symptoms associated with attention deficit, impulsivity, and hyperactivity. More studies on larger samples are necessary to assess the differential risks for adolescent smoking initiation that are associated with ADHD subtypes and with ODD and CD comorbidities.
*Citation: Gehricke, J.-G., Loughlin, S., Whalen, C., Potkin, S., Fallon, J., Jamner, L., … Leslie, F. (2007). Smoking to self-medicate attentional and emotional dysfunctions. Nicotine Tobacco Research, 9, 523–536. https://doi.org/10.1080/14622200701685039

===2007: [https://pubmed.ncbi.nlm.nih.gov/18022679/ Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.
**Citation: Potter AS, Newhouse PA. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav. 2008 Feb;88(4):407-17. doi: 10.1016/j.pbb.2007.09.014. Epub 2007 Sep 26. PMID: 18022679.
***Acknowledgement: Paywalled, unable to access.

===2006 [https://www.academia.edu/17983526/The_reinforcing_effects_of_nicotine_and_stimulant_medication_in_the_everyday_lives_of_adult_smokers_with_ADHD_A_preliminary_examination The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination]===
*The findings suggest that smokers with ADHD experience nicotine-related reductions in ADHD symptoms during their everyday lives.
*Citation: Gehricke, J. G., Whalen, C., Jamner, L., Wigal, T., & Steinhoff, K. (2006). The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination. Nicotine Tobacco Research, 8(1), 37–47. https://doi.org/10.1080/14622200500431619

===2006 [https://www.sciencedirect.com/science/article/abs/pii/S0031938405005627?via%3Dihub Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits]===
*The results showed nicotine-induced improvement on some measures of sustained attention in the low attention group and some decrement in working memory in the high attention group, which suggests that nicotine tends to optimize rather than improve performance on cognitive tasks.
*[https://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]
*Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2003: [https://www.academia.edu/2412608/Is_There_a_Link_Between_Adolescent_Cigarette_Smoking_and_Pharmacotherapy_for_ADHD Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?]===
*Self-report surveys, electronic diaries, and salivary cotinine all indicated that adolescents treated with pharmacotherapy for ADHD smoked less than their untreated counterparts over 2 years of high school. These convergent findings from 3 disparate indicators lend support to the self-medication hypothesis over the gateway hypothesis, although alternative explanations need further study. The findings also suggest that early treatment of psychological and behavioral problems may prevent or delay smoking initiation
*Citation: Whalen, C. K., Jamner, L. D., Henker, B., Gehricke, J.-G., & King, P. S. (2003). Is There a Link Between Adolescent Cigarette Smoking and Pharmacotherapy for ADHD? Psychology of Addictive Behaviors, 17(4), 332–335. https://doi.org/10.1037/0893-164X.17.4.332

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===2001 [https://psycnet.apa.org/record/2001-14365-012 Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder.]===
*This small study (40 participants) provided evidence that nicotine treatment can reduce severity of attentional deficit symptoms and produce improvement on an objective computerized attention task.
*Citation: Levin, E. D., Conners, C. K., Silva, D., Canu, W., & March, J. (2001). Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Experimental and Clinical Psychopharmacology, 9(1), 83–90. https://doi.org/10.1037/1064-1297.9.1.83

===1998 [https://pubmed.ncbi.nlm.nih.gov/9860103/ Transdermal nicotine effects on attention]===
*This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult non-smokers.
*[https://sci-hub.st/10.1007/s002130050750 PDF Version]
*Citation: Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J, Rose JE. Transdermal nicotine effects on attention. Psychopharmacology (Berl). 1998 Nov;140(2):135-41. doi: 10.1007/s002130050750. PMID: 9860103
*Acknowledgement: The authors thank R.J. Reynolds for financial support of the project. Work on this article was partially supported by Career Science Award (K05MH0122903) to Dr. Conners and Research Scientist Development Award (K02MH0098102) to Dr. March

===1996 [https://pubmed.ncbi.nlm.nih.gov/8741955/ Nicotine effects on adults with attention-deficit/hyperactivity disorder]===
*Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clinical trials with ADHD.
*[https://sci-hub.st/10.1007/BF02246281 PDF Version]
*Citation: Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl). 1996 Jan;123(1):55-63. doi: 10.1007/BF02246281. PMID: 8741955.
*Acknowledgement: The authors thank Dr. Allen Frances, Chairman of the Department of Psychiatry, Duke University Meidcal Center for his finanical support of the project. Work on this article was partially supported by Career Science Award (K05MH01229-03) to Dr. Conners and Research Scientist Development Award (K20MH00981-02) to Dr. March and a Young Investigator Award from the National Alliance for Research Schizophenia and Depression to Dr. Levin.

===1996: [https://pubmed.ncbi.nlm.nih.gov/8927677/ Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD)]===
*The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.
*Citation: Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull. 1996;32(1):67-73. PMID: 8927677.

===Year Unknown: Article: [https://www.adxs.org/en/page/192/nicotine-as-a-medication-for-adhd Nicotine as a medication for ADHD]===
*Lists references

 

='''Aging'''=

===2023: [https://www.nature.com/articles/s41467-023-36543-8 Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity]===
*Abstract "Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms."
**Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8
***Acknowledgement: This work was supported by grants from Shenzhen Science and Technology Program (KQTD20210811090117032), Shenzhen Key Laboratory of Viral Vectors for Biomedicine (ZDSYS20200811142401005), CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024) and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).

='''Akathisia'''=

===1997: [https://pubmed.ncbi.nlm.nih.gov/9399378/ Treatment of neuroleptic-induced akathisia with nicotine patches]===
*We administered 14 mg nicotine patches to 16 patients, all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia.
*[https://sci-hub.se/10.1007/s002130050436 PDF Version]
**Citation: Anfang MK, Pope HG Jr. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl). 1997 Nov;134(2):153-6. doi: 10.1007/s002130050436. PMID: 9399378.
 

='''Alcohol Use Disorder'''=

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

='''Allergies / Hayfever / Histamines''' (See also: Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis)=

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203434/ Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation]===
*Animal Study
*In this study, the effect of environmental tobacco smoke (ETS) on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated.
*In summary, ETS suppressed allergen-induced nasal responses including NHR by inhibiting allergen-specific Th2 cell responses. Although our present findings do not deny harmful effects of cigarette smoking, nicotine as a component of ETS may be a target to treat Th2-mediated allergic diseases, including allergic rhinitis (AR).
**Citation: Nishimura T, Kaminuma O, Saeki M, Kitamura N, Mori A, Hiroi T. Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation. Asia Pac Allergy. 2020 Apr 27;10(2):e18. doi: 10.5415/apallergy.2020.10.e18. PMID: 32411583; PMCID: PMC7203434.
***Acknowledgement: This work was supported in part by funding from the Smoking Research Foundation provided to Osamu Kaminuma.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440386/ Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium]===
*Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
**Citation: Skaaby T, Taylor AE, Jacobsen RK, et al. Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Sci Rep. 2017 May 22;7(1):2224. doi: 10.1038/s41598-017-01977-w. PMID: 28533558; PMCID: PMC5440386.
***Acknowledgement: This work was supported by the Medical Research Council (grant numbers: MR/J01351X/1, MC_UU_12013/6). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

===2014: [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085888 Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model]===
*Animal study
*In this study, nicotine treatment significantly ameliorated FA [Food Allergy], mainly due to the suppression of upregulated mucosal immune responses via α7 nAChRs on immune cells. Therefore, the therapeutic effects of nicotine and GTS-21 on the FA model raise the possibility that a strategy for drug discovery against FA by targeting α7 nAChRs could potentially have therapeutic benefits.
**Citation: Yamamoto T, Kodama T, Lee J, Utsunomiya N, Hayashi S, Sakamoto H, Kuramoto H, Kadowaki M. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS One. 2014 Jan 16;9(1):e85888. doi: 10.1371/journal.pone.0085888. PMID: 24454942; PMCID: PMC3894205.

===2008: [https://journals.aai.org/jimmunol/article/180/11/7655/84640/Nicotine-Primarily-Suppresses-Lung-Th2-but-Not Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens]===
*Animal Study
*hese results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia, mucous production, and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
**Citation: Neerad C. Mishra, Jules Rir-sima-ah, Raymond J. Langley, Shashi P. Singh, Juan C. Peña-Philippides, Takeshi Koga, Seddigheh Razani-Boroujerdi, Julie Hutt, Matthew Campen, K. Chul Kim, Yohannes Tesfaigzi, Mohan L. Sopori; Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens1. J Immunol 1 June 2008; 180 (11): 7655–7663. https://doi.org/10.4049/jimmunol.180.11.7655
***Acknowledgement: This work was supported in part by grants from the National Institutes of Health (R01-DA017003, R01-DA04208-15, and R01-DA042087S).

===2004: [https://link.springer.com/article/10.1007/s00011-004-1249-1 The effect of nicotine on basophil histamine release]===
*This study has demonstrated that nicotine agonists inhibit histamine release from human basophils.
*[https://sci-hub.st/10.1007/s00011-004-1249-1 PDF Full Version]
**Citation: Thompson-Cree, M.E.M., Stevenson, M.R., Shields, M.D. et al. The effect of nicotine on basophil histamine release. Inflamm. res. 53, 211–214 (2004). https://doi.org/10.1007/s00011-004-1249-1

='''Alzheimer / Dementia / Mild Cognitive Imparement (MCI)'''=
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

===2013 [https://link.springer.com/article/10.1007/s12017-013-8242-1 Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation]===
*Animal Study
*Taken together, these results demonstrate that nicotine prevents memory deficits and synaptic impairment induced by Aβ oligomers. In addition, nicotine improves memory in young APP/PS1 transgenic mice before extensive amyloid deposition and senile plaque development, and also in old mice where senile plaques have already formed.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/s12017-013-8242-1 PDF Version]
*Citation: Inestrosa, N.C., Godoy, J.A., Vargas, J.Y. et al. Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation. Neuromol Med 15, 549–569 (2013). doi: 10.1007/s12017-013-8242-1
*Acknowledgements: We thank Dr. Rodrigo Varas for his help with the electrophysiological studies of the α7-nAChR. This work was supported by a grant from FONDECYT No 120156 to N.C.I; predoctoral fellowships from CONICYT to G.G.F., M.S.A. F.G.S., J.A.R. and from Fundación Gran Mariscal de Ayacucho to J.Y.V. The Basal Center of Excellence in Science and Technology CARE was funded by CONICYT/PFB 12/2007.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/ Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment.
*Safety and tolerability for transdermal nicotine were excellent.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/pdf/znl91.pdf PDF Version]
*Citation: Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology. 2012 Jan 10;78(2):91-101. doi: 10.1212/WNL.0b013e31823efcbb. PMID: 22232050; PMCID: PMC3466669.

===2010 [https://www.tandfonline.com/doi/abs/10.1080/13607860220126808 Nicotine's effect on neural and cognitive functioning in an aging population]===
*Recent advances in nicotine research have pointed to a number of cognitive and neurological benefits that have been linked to the ingestion of nicotine.
*This article examines cognitive decline in the elderly and looks at nicotine's potential role in ameliorating this decline.
*Nicotine’s effects on cognitive functioning have shown it to increase perception, visual attention,and arousal as well as improving the speed and accuracy of motor functioning while decreasing reaction time and inhibiting declines in efficiency. In addition, research has shown nicotine to improve long-term and short-term memory, and to increase the ability to withhold inappropriate responses.
*Research has revealed that chronic exposure to nicotine produces an unusual up-regulation of the nicotinic receptor sites. This increase in receptor sites is thought to provide some protection against neuro-degenerative disorders such as Alzheimer’s disease.
*[https://sci-hub.st/10.1080/13607860220126808 PDF Version]
*Citation: K. N. Murray & N. Abeles (2002) Nicotine's effect on neural and cognitive functioning in an aging population, Aging & Mental Health, 6:2, 129-138, DOI: 10.1080/13607860220126808

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783.
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12436427/ Nicotinic receptors in aging and dementia]===
*Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects.
*Acute nicotine administration can improve performance of patients with AD on cognitive tasks, including verbal learning and memory, attention in a continuous performance task, and accuracy in a visual attention task.
*In addition to its ability to reverse cognitive deficits following aging, nicotine has been shown to protect against neurotoxic insult in vitro and in vivo. This suggests that nicotine has a dual effect on brain function following aging or injury, such that it can rescue function of remaining neurons, as well as saving neurons that might otherwise undergo cell death.
*[https://sci-hub.st/10.1002/neu.10102 PDF Version]
*Citation: Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. J Neurobiol. 2002 Dec;53(4):641-55. doi: 10.1002/neu.10102. PMID: 12436427.
*Keywords: nAChR; neuroprotection; Alzheimer’s disease; Parkinson’s disease; acetylcholine

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Alzheimer's disease (AD)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1410164/ Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease]===
*Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds).
*[https://sci-hub.st/10.1007/BF02247426 PDF Version]
*Citation: Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology (Berl). 1992;108(4):485-94. doi: 10.1007/BF02247426. PMID: 1410164.
*Acknowledgements. This research was supported by British-American Tobacco Co. Ltd. BJS thanks the Wellcome Trust and the Eleanor Peel Foundation for support.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in enhancement of performance, and protection against Alzheimer's disease (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1989 [https://pubmed.ncbi.nlm.nih.gov/2597885/ The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type]===
*Nicotine in patients with dementia of the Alzheimer type (DAT) produced a significant and marked improvement in discriminative sensitivity and reaction times on a computerised test of attention and information processing. Nicotine also improved the ability of DAT patients to detect a flickering light in a critical flicker fusion test. These results suggest that nicotine may be acting on cortical mechanisms involved in visual perception and attention, and support the hypothesis that acetylcholine transmission modulates vigilance and discrimination. Nicotine may therefore be of some value in treating deficits in attention and information processing in DAT patients.
*[https://sci-hub.st/10.1192/bjp.154.6.797 PDF Version]
*Citation: Sahakian B, Jones G, Levy R, Gray J, Warburton D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry. 1989 Jun;154:797-800. doi: 10.1192/bjp.154.6.797. PMID: 2597885.
 

='''Antimicrobial Agent'''=
*As a follow-up to these provocative findings, future related studies should examine whether nicotine exerts its anti-microbial effects against a much broader range of indigenous microflora than has been studied so far, along with focusing on the molecular biologic mechanisms and host pathologic changes associated with nicotine-mediated killing of the oral and intestinal microflora.
**Citation: Pavia CS, Plummer MM. Clinical implications of nicotine as an antimicrobial agent and immune modulator. Biomed Pharmacother. 2020 Sep;129:110404. doi: 10.1016/j.biopha.2020.110404. Epub 2020 Jun 27. PMID: 32603888; PMCID: PMC7320263.
***Acknowledgement: This work was partially supported by funds provided by the Department of Biomedical Sciences, NYIT College of Osteopathic Medicine. The authors thank the publisher of the Journal of Medical Microbiology (JMM) for granting us permission to reuse in this paper, without being subject to any copyright infringement, some of the material previously published by one of us (CSP) in the JMM. We also thank Jane Pavia for contributing to the design of the graphical abstract.
 

='''Aphthous ulcers''' (See also: Behcet's disease)=

===2015: [https://pmc.ncbi.nlm.nih.gov/articles/PMC4387635/ Use of pure nicotine for the treatment of aphthous ulcers]===
*The theory that nicotine is known as the protective factor is also supported by three case reports, in which aphthous ulcers were prevented or healed while the patients used nicotine replacement materials.
*To summarize, the use of pure nicotine in therapeutic forms, seems to be a proper alternative to treat aphthous ulcers; however, there has not been any evidence-based case-control study to prove such claim.
**Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

===2014: [https://pubmed.ncbi.nlm.nih.gov/25584320/ Recurrent aphthous ulcers among tobacco users- hospital based study]===
*The tobacco consumers have less frequency of aphthous ulceration compared non users.
**Citation: Mohamed S, Janakiram C. Recurrent aphthous ulcers among tobacco users- hospital based study. J Clin Diagn Res. 2014 Nov;8(11):ZC64-LC66. doi: 10.7860/JCDR/2014/10368.5145. Epub 2014 Nov 20. PMID: 25584320; PMCID: PMC4290331.

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2004: [https://pubmed.ncbi.nlm.nih.gov/15370162/ The relationship between smoking cessation and mouth ulcers]===
*Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.
**Citation: McRobbie H, Hajek P, Gillison F. The relationship between smoking cessation and mouth ulcers. Nicotine Tob Res. 2004 Aug;6(4):655-9. doi: 10.1080/14622200410001734012. PMID: 15370162.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===
*This study shows that a group of RAS patients is significantly less likely to contain smokers than a matched control population, and among smokers the level of cigarette use was significantly lower in RAS patients than the control population. The perceived negative association between RAS and smoking was supported by this epidemiological study.
*[https://sci-hub.st/10.1034/j.1601-0825.2002.01826.x PDF Version]
**Citation: Atkin PA, Xu X, Thornhill MH. Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Dis. 2002 May;8(3):173-6. doi: 10.1034/j.1601-0825.2002.01826.x. PMID: 12108762.

===2000: [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418

===1992: [https://pubmed.ncbi.nlm.nih.gov/1408021/ Smokeless tobacco use prevents aphthous stomatitis]===
*In (contrast to cigarette smoking, however, few components other than nicotine are systemically absorbed by ST users. Thus if the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.
*[https://sci-hub.se/10.1016/0030-4220(92)90296-3 PDF Version]
**Citation: Grady D, Ernster VL, Stillman L, Greenspan J. Smokeless tobacco use prevents aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):463-5. doi: 10.1016/0030-4220(92)90296-3. PMID: 1408021.

===1991 [https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1991.tb121180.x?sid=nlm%3Apubmed Recurrent aphthous ulcers and nicotine]===
*The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers.
*[https://sci-hub.st/10.5694/j.1326-5377.1991.tb121180.x PDF Version]
**Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x
 

='''Arthritis/Skeletal'''=

==Osteoarthritis==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2019 [https://journals.aai.org/jimmunol/article/203/2/485/107400/Nicotine-Attenuates-Osteoarthritis-Pain-and-Matrix Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor]===
*In conclusion, stimulation of α7-nAChRs by nicotine attenuates MIA-induced OA pain and cartilage degradation. This protective effect of nicotine can be associated with the inhibition of MMP-9 overexpression through the PI3K/Akt/NF-κB signaling pathway. Although the use of nicotine is limited by its nonspecific effects, this study provides novel evidence supporting the future development of therapeutic strategies for inflammatory diseases via the cholinergic anti-inflammatory pathway.
**Citation: Teng P, Liu Y, Dai Y, Zhang H, Liu WT, Hu J. Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor. J Immunol. 2019 Jul 15;203(2):485-492. doi: 10.4049/jimmunol.1801513. Epub 2019 May 31. PMID: 31152077.
***This work was supported by grants from the National Natural Science Foundation of China (81373397, 81672218, and 81603092) and the Department of Science, Education, and Health Program of Jiangsu Province (QNRC 2016606 and QNRC 2016604).

==Rheumatoid arthritis (collagen-induced arthritis CIA in mice)==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2016 [https://www.spandidos-publications.com/mmr/14/6/5057 Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration]===
*Animal study
*Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.
**Citation: Li S, Zhou B, Liu B, Zhou Y, Zhang H, Li T, Zuo X. Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration. Mol Med Rep. 2016 Dec;14(6):5057-5064. doi: 10.3892/mmr.2016.5904. Epub 2016 Oct 31. PMID: 27840928; PMCID: PMC5355730.
***Acknowledgement: The present study was supported by a grant from the National Natural Science Foundation of China (grant no. 81571602).

===2014 [https://pubmed.ncbi.nlm.nih.gov/24313917/ Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells]===
*Animal Study
*Nicotine stimulation attenuated signs and severity of arthritis in mice. Activation of nicotine acetylcholine receptors on in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may play a potential role in alleviating arthritis in mice.
*[https://sci-hub.st/10.3109/14397595.2013.862352 PDF Full paper]
**Citation: Yang Y, Yang Y, Yang J, Xie R, Ren Y, Fan H. Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells. Mod Rheumatol. 2014 Sep;24(5):781-7. doi: 10.3109/14397595.2013.862352. Epub 2013 Dec 9. PMID: 24313917.
***Acknowledgement: This work was supported by The Shanghai Committee of Science and Technology Project, China (Grant No. 12GWZX0201,11140902900).

===2014 [https://www.sciencedirect.com/science/article/abs/pii/S0014299914003033 Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine]===
*Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses, may improve the Th1/Th2 imbalance in CIA, and provide a new justification for its application in the clinical treatment of RA.
*[https://sci-hub.st/10.1016/j.ejphar.2014.04.019 PDF Full paper]
**Citation: Wu S, Luo H, Xiao X, Zhang H, Li T, Zuo X. Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol. 2014 Jul 15;735:97-104. doi: 10.1016/j.ejphar.2014.04.019. Epub 2014 Apr 19. PMID: 24755145.
***Acknowledgement: This work was supported by a grant from the National Natural Science Foundation of China, People's Republic of China [81102261] and the Innovative Research Funds for the Central South University, People's Republic of China. [CX2012B088].

===2009 [https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.24177 Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice]===
*Animal Study
*Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction.
**Citation: van Maanen MA, Lebre MC, van der Poll T, LaRosa GJ, Elbaum D, Vervoordeldonk MJ, Tak PP. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 2009 Jan;60(1):114-22. doi: 10.1002/art.24177. PMID: 19116908.

='''Ataxia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

= '''Auditory''' =

===2021 [https://www.nature.com/articles/s41598-021-92588-z Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers]===
*The present study evaluated acute effects of oral nicotine treatment on three auditory tasks in young adult and elderly, healthy, non-smoking individuals. All had normal hearing within the frequency range of the stimuli presented for the three tasks. Compared to pre-treatment performance, nicotine improved frequency discrimination. Compared to placebo, nicotine produced no overall effects on the two frequency related tasks, but significantly improved intensity discrimination, with more improvement obtained for those who had lower baseline performance. The present results support the hypothesis that nicotine enhances auditory processing, but this enhancement is task-dependent.
*[https://www.nature.com/articles/s41598-021-92588-z.pdf PDF Version]
*Citation: Sun, S., Kapolowicz, M.R., Richardson, M. et al. Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers. Sci Rep 11, 13187 (2021). doi: 10.1038/s41598-021-92588-z

===2019 [https://pubmed.ncbi.nlm.nih.gov/31832719/ Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers]===
*Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.
*[https://sci-hub.se/10.1007/s00213-019-05421-x PDF Version]
*Citation: Pham CQ, Kapolowicz MR, Metherate R, Zeng FG. Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers. Psychopharmacology (Berl). 2020 Mar;237(3):833-840. doi: 10.1007/s00213-019-05421-x. Epub 2019 Dec 12. PMID: 31832719; PMCID: PMC7039769.
*Acknowledgements: This research was supported by grants from the National Institutes of Health to FGZ (5R01DC015587), to RM (4R01-DC013200) and a pre-doctoral fellowship to CQP (UL1-TR000153).
*Keywords: Acetylcholinergic systems; Auditory processing; Nicotine; Selective attention; Spectral ripple discrimination; Temporal gap detection; Tone in noise detection.

='''Autism'''=

===2025: [https://link.springer.com/article/10.1007/s12035-025-04894-6 Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism]===
*Animal Study
*Accumulating evidence indicates that nicotinic receptor subtypes are altered in the brains of autistic individuals, and nicotinic acetylcholine receptors (nAChRs) play essential roles in autistic profiles in BTBR T+ Itpr3tf/J mice.
*Biochemical analysis showed that nicotine had significantly decreased the concentration of inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, and GM-CSF in the serum, and reduced the expression levels of intracellular pro-inflammatory cytokines (IL-17 & IFN-γ) on CD4+ and CD8+ T cells in the blood while mecamylamine reversed the effect of IL-17+ CD4+ T cells.
*Nicotine administration up-regulated the expressions of α7, α4, and β2 nAChRs in the prefrontal cortex in BTBR T+ Itpr3tf/J mice.
*The current results indicate that nAChRs play a significant role, at least in part, in ASD and might serve as a crucial target for therapeutic interventions in ASD.
**Citation: AlSharari, S.D., Mahmood, H.M., Alasmari, A.F. et al. Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism. Mol Neurobiol (2025). https://doi.org/10.1007/s12035-025-04894-6
***Acknowledgement: Researchers Supporting Project number (RSPD2025R829), King Saud University, Riyadh, Saudi Arabia. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

===2020: [https://pubmed.ncbi.nlm.nih.gov/32691528/ The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model]===
*Animal Study
*Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people.
*Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism.
*Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model.
*LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.
*[https://sci-hub.st/10.1002/aur.2342 PDF Full paper]
**Citation: Mahmood HM, Aldhalaan HM, Alshammari TK, Alqasem MA, Alshammari MA, Albekairi NA, AlSharari SD. The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model. Autism Res. 2020 Aug;13(8):1311-1334. doi: 10.1002/aur.2342. Epub 2020 Jul 21. PMID: 32691528.
***Acknowledgement: The authors would like to thank the support from the Center for Autism Research (CFAR), King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia.

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
**Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
***Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).

===2016: [https://pmc.ncbi.nlm.nih.gov/articles/PMC5101145/ Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia]===
*Animal Study
*
**Citation:
***Acknowledgement:

===2016: [https://pubmed.ncbi.nlm.nih.gov/27638450/ Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system]===
*Animal Study
*
*[https://sci-hub.st/10.1016/j.neuropharm.2016.09.013 PDF Full paper]
**Citation:
***Acknowledgement:

===2015: [https://pubmed.ncbi.nlm.nih.gov/26337613/ Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system]===
*Animal Study
*
**Citation:
***Acknowledgement:
 

='''Behcet's disease''' (See also: Aphthous ulcers)=
*Post on [https://healthunlocked.com/behcetsuk/posts/138632782/nicotine-and-it%E2%80%99s-effects-on-my-beh%C3%A7et%E2%80%99s-for-the-positive Behçet's UK]. A person started smoking seeking relief from the pain they suffered because of Behcet's disease.

===2010 [https://academic.oup.com/rheumatology/article/49/3/501/1786816 Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series]===
*In this report, we describe five ex-smoker [[Special:MyLanguage/Abbreviations|'''BD''']] patients with active mucocutaneous lesions, not responsive to standard pharmacological treatments and treated with transdermal nicotine patches. Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of all mucocutaneous lesions within 6 months of observation.
**Citation: Giovanni Ciancio, Matteo Colina, Renato La Corte, Andrea Lo Monaco, Francesco De Leonardis, Francesco Trotta, Marcello Govoni, Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series, Rheumatology, Volume 49, Issue 3, March 2010, Pages 501–504, doi: 10.1093/rheumatology/kep401

===2007 [https://www.jidonline.org/article/S0022-202X(15)33112-2/fulltext Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease]===
*"In conclusion, we observed substantial inhibitory effects of CSE and nicotine on IL-8 and to a lesser extent on IL-6 release by human keratinocytes and HMEC-1 endothelial cells. These findings may explain the beneficial effect of smoking in BD, also because IL-8, and to some extent IL-6, are likely to induce pivotal proinflammatory signals in this disease (Lee et al., 1993). Nicotine may cause immunoregulation by affecting chemokine/cytokine production. This study also demonstrates the different behavior of cells in terms of cytokine release when stimulated with BD patients' sera compared to those of healthy individuals. The in vitro evidence of beneficial effects of nicotine in BD is fundamental to our ongoing clinical trial with nicotine transdermal patches in BD. In addition, the detected beneficial effect of biochanin A implicates this compound as a candidate for future developments in aphthae treatment. The development of topical nicotinic cholinergic receptor subtype-specific agonists is likely to exhibit beneficial effects on skin and mucosae without inducing systemic adverse effects."
**Citation: Kalayciyan A, Orawa H, Fimmel S, Perschel FH, González JB, Fitzner RG, Orfanos CE, Zouboulis CC. Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease. J Invest Dermatol. 2007 Jan;127(1):81-9. doi: 10.1038/sj.jid.5700492. Epub 2006 Sep 28. PMID: 17008886.
***Acknowledgement: Dr Kalayciyan was supported by a grant of the Berlin Foundation for Dermatology. The research project was supported by the Deutsches Register Morbus Adamantiades–Behçet e.V.

===2000 [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418
 

='''Brain Injuries, Strokes, Brain Diseases'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/39921606/ The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]===
*Animal Study
*The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke. This finding suggests that targeting the BBB, especially endothelial cells, with nicotine treatment is a promising therapeutic strategy for brain injury after ischemic stroke.
**Citation: Pang Q, Yan X, Chen Z, Yun L, Qian J, Dong Z, Wang M, Deng W, Fu Y, Hai T, Chen Z, Rong X. The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier. Nicotine Tob Res. 2025 Feb 8:ntaf034. doi: 10.1093/ntr/ntaf034. Epub ahead of print. PMID: 39921606.
***Acknowledgement: Paywalled, unable to access

===2024: [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://pubmed.ncbi.nlm.nih.gov/38698493/ Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury]===
*Animal study
*Conclusioin: "Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions."
**Citation: Wang D, Li X, Li W, Duong T, Wang H, Kleschevnikova N, Patel HH, Breen E, Powell S, Wang S, Head BP. Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury. Br J Pharmacol. 2024 Sep;181(17):3082-3097. doi: 10.1111/bph.16395. Epub 2024 May 2. PMID: 38698493.
***Acknowledgement: H. H. P. and B. P. H. hold equity and are non-paid consultants with Eikonoklastes Therapeutics LLC. Funding information: (TRDRP 2020 T31IR1834 to BPH, VA Merit BX003671 and VA RCS BX006318 to BPH, AL210059 to BPH, Craig H. Neilsen Foundation 886964 to SW and BX005229 to HHP).

===2004: [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===
*Several studies have shown that nicotine treatment can attenuate cognitive deficits produced by medial septal lesions, lesions of the nucleus basalis, and traumatic brain injury.
*[https://sci-hub.st/10.1196/annals.1332.019 PDF Version]
**Citation: Pauly JR, Charriez CM, Guseva MV, Scheff SW. Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease. Ann N Y Acad Sci. 2004 Dec;1035:316-34. doi: 10.1196/annals.1332.019. PMID: 15681815.
***Acknowledgements: This work was supported by grants from the National Institutes of Health (NS42196 to J.R.P. and NS39828 to S.W.S.) and the Kentucky Tobacco Research and Development Center. We acknowledge the technical assistance of Melissa Yingling and Khaled Tanwir.

='''Cancer / Cancer Treatments'''=
===2021 [https://www.mdpi.com/1660-3397/19/2/118 α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells]===
*Animal Study
*We tested the effects of nicotine, which is an agonist for all nAChRs with the exception of α9 subtype for which it is antagonist. At concentrations of 0.001–0.1µL/mL (6.1 µM–0.61 mM), nicotine exerted no effect on the proliferative activity of glioma C6 cells and the loss of viability was 1–4% (Figure S2). Analysis by light microscopy showed that nicotine at concentrations of 1 µL/mL (6.1 mM) and higher induced morphological changes like cell rounding up and loss of processes followed by surface detachment (Figure 3). Despite these changes, we investigated the effect of nicotine at a concentration of 1 μL/mL (6.1 mM) on the proliferation and viability of C6 cells. At this nicotine concentration, inhibition of proliferation was observed, which after 72 h led to a decrease in the number of cells by more than two times; the viability was also reduced (Figure S2). However, it should be taken into account that the reason for such a strong decrease in the concentration of cells may be their detachment from the surface and, as a consequence, the cessation of division. We tested acetylcholine at concentrations ranging from 2 µM to 2 mM with incubation times of 24, 48 and 72 h. No effects of acetylcholine were observed.
**Citation: Terpinskaya, T. I., Osipov, A. V., Kryukova, E. V., Kudryavtsev, D. S., Kopylova, N. V., Yanchanka, T. L., Palukoshka, A. F., Gondarenko, E. A., Zhmak, M. N., Tsetlin, V. I., & Utkin, Y. N. (2021). α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Marine Drugs, 19(2), 118. https://doi.org/10.3390/md19020118
***Acknowledgement: This work was supported by the Belarusian Republican Foundation for Fundamental Research, project number M20R-254, and the Russian Foundation for Basic Research, project number 20-54-00033.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S001448272030416X?via%3Dihub Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells]===
*Nicotine inhibits ovarian cancer cell ERK and p38 [[Special:MyLanguage/Abbreviations|'''MAPK''']] signaling.
*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]
**Citation: Sarah J. Harmych, Jay Kumar, Mesa E. Bouni, Deborah N. Chadee, Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells, Experimental Cell Research, Volume 394, Issue 1, 2020, 112167, ISSN 0014-4827, doi: 10.1016/j.yexcr.2020.112167.
***Acknowledgements: This work was supported by the National Institutes of Health [R15 CA199164] and [R15 CA241898] to D.N.C.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

='''Cannabis / THC'''=
===2020 [https://pubmed.ncbi.nlm.nih.gov/32034447/ Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial]===
*The findings provide the first evidence that [[Special:MyLanguage/Abbreviations|NP (Nicotine Patch)]] may be able to attenuate NA (negative affect) - related withdrawal symptoms in individuals with cannabis use disorder who are not heavy users of tobacco or nicotine.
*[https://sci-hub.se/10.1007/s00213-020-05476-1 PDF Version]
*Citation: Gilbert DG, Rabinovich NE, McDaniel JT. Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial. Psychopharmacology (Berl). 2020 May;237(5):1507-1519. doi: 10.1007/s00213-020-05476-1. Epub 2020 Feb 7. PMID: 32034447.
*Acknowledgement: The study was supported by NIH grant R01DA031006 awarded to David Gilbert.
*Keywords: Cannabis; Marijuana; Negative affect; Nicotine; Smoking; THC; Testing effect; Withdrawal symptoms.

= '''Cardiovascular''' =
*See also: Brain Injuries and Strokes

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38529793/ Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects] ===
* This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers.
* PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
* Nicotine patches appear to promote blood vessel formation, without adverse effects.

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2015 [https://www.nature.com/articles/srep15895 Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3] ===

* The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis.
* The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group.
* The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
* Animal study (mice)
* Ge Li-Sha, Zhao Jing-Lin, Chen Guang-Yi, Liu Li, Zhou De-Pu & Li Yue-Chun ''Scientific Reports'' volume 5, Article number: 15895 (2015)

='''Chlamydia Pneumoniae'''=
*Chlamydia pneumoniae is a type of bacteria that can cause respiratory tract infections, such as pneumonia. C. pneumoniae is one cause of community-acquired pneumonia or lung infections developed outside of a healthcare setting. However, not everyone exposed to C. pneumoniae will develop pneumonia. [https://www.cdc.gov/pneumonia/atypical/cpneumoniae/index.html Source: US CDC]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''Cognitive / IQ / Memory'''=
*See also: Sleep - REM

=== 2024: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/ An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence] ===
*Conclusion: Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.
*Citation: Harry J. Green, Olivia K. O’Shea, Jack Cotter, Helen L. Philpott, and Nik Newland. Harm Reduct J. 2024; 21: 78. Published online 2024 Apr 6. doi: 10.1186/s12954-024-00993-0 PMCID: PMC10998423

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnins.2023.1252705/full Editorial: Nicotine and its derivatives in disorders of cognition: a challenging new topic of study] ===

* Front. Neurosci., 18 July 2023 Sec. Neurodegeneration Volume 17 - 2023 | <nowiki>https://doi.org/10.3389/fnins.2023.1252705</nowiki>
* Albert Gjedde, Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
* Nicotine is a compound of considerable interest to neuroscience, in contexts of physiology as well as pathology of brain functions related to neurotransmitter mechanisms. Nicotine is an alkaloid that exists naturally in plants such as tomatoes and potatoes, with the highest levels in the tobacco plant.
* In mammalian brains, nicotine has multiple actions that appear to be accidents of evolution, as no specific relation springs to mind between the functions of nicotine in plants and animals.
* The following discussion expands upon the three topics of biology, therapy, and possible prevention, as related to cognition, in the three reviews and the three original studies included in the collection.
** Conclusion: Questions remain of how nicotine treatment in normal aging should proceed, including length of treatment, dose of nicotine, handling of smokers, effects of AD risk factors, and many others. While data from studies of psychiatric and memory-impaired subjects indicate that nicotine may relieve cognitive symptoms, it is mandatory to test the benefits of nicotine in normal aging in order to fill gaps in the literature and to verify the extent to which nicotine is useful as a pharmacologic agent that prevents pathological aging.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36736944/ Nicotine's effect on cognition, a friend or foe?] ===
* In this review, we first introduce the beneficial effect of nicotine on cognition including attention, short-term memory and long-term memory. We next summarize the beneficial effect of nicotine on cognition under pathological conditions, including Alzheimer's disease, Parkinson's disease, Schizophrenia, Stress-induced Anxiety, Depression, and drug-induced memory impairment.
* We can only access the abstract, but would be interested to read the whole thing if anyone can help?
* Human study
* Qian Wang, Weihong Du, Hao Wang, Panpan Geng, Yanyun Sun, Junfang Zhang, Wei Wang, Xinchun Jin, PMID: 36736944 DOI: 10.1016/j.pnpbp.2023.110723

=== 2021: [https://www.spandidos-publications.com/10.3892/mmr.2021.12037# Molecular insights into the benefits of nicotine on memory and cognition] ===

* Published online on: March 25, 2021 Molecular Medicine Reports <nowiki>https://doi.org/10.3892/mmr.2021.12037</nowiki> Article Number: 398
* Author: Ahmad Alhowail

===2021: [https://www.sciencedirect.com/science/article/abs/pii/S1001841721007804 Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS]===
*Animal study
*Exposure to nicotine mainly altered the secretion of serotonin, kynurenic acid, choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition, and the change are closely related to the dose and duration of exposure.
**Citation: Chen Z, Fu L, Liu X-A, Yang Z, Li W, Li F, Luo Q. Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS. Chin Chem Lett. 2022;33(6):3101–5.
***Acknowledgement: This work was financially supported by the National Natural Science Foundation of China (No. 22076197), the Scientific Instrument Developing Project of the Chinese Academy of Sciences (No. YJKYYQ20200034), Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development (No. XMHT20190204002), Shenzhen Science and Technology Innovation Commission (No. JCYJ20200109115405930), Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020B1515120080).
*Article: [https://medicalxpress.com/news/2021-10-reveal-nicotine-hippocampal-dependent-cognition.html Researchers reveal how nicotine influences hippocampal-dependent cognition] "These results suggested the acute exposure to nicotine was beneficial to protect the neurons, especially cognitive enhancement, and the elevated picolinic acid continually protected neuronal cognitive function after nicotine withdrawal. Furthermore, the dynamic alterations of neurotransmitter metabolism induced by nicotine might be a possible protective mechanism of nicotine on hippocampal dependent cognition."

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0306452220304723?via%3Dihub Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study]===
*Nicotine improves sustained attention and reduces distractor interference, promoting cognitive stability. Nicotine enhances response times without differential impact on task switching or distraction.
*[https://sci-hub.se/10.1016/j.neuroscience.2020.07.029 PDF Version]
*Citation: Stefan Ahrens, Christiane M. Thiel, Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study, Neuroscience, Volume 444, 2020, Pages 43-53, ISSN 0306-4522, doi: 10.1016/j.neuroscience.2020.07.029.
*Acknowledgements: This work was supported by a grant from the German Research Foundation DFG TH766/8-1.
*Key words: nicotine, cholinergic, cognitive control, distraction, task switching, neuroimaging

===2019: [https://www.frontiersin.org/articles/10.3389/fnins.2018.01002/full#B5 Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review]===
*Nicotine lowers learning and memory impairment in some neurological disorders.
*Citation: Majdi, A., Kamari, F., & Gjedde, A. (2019). Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.01002

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.nature.com/articles/npp201715 Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention]===
*Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory–inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.
**Citation: Bueno-Junior, L., Simon, N., Wegener, M. et al. Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Neuropsychopharmacol 42, 1590–1598 (2017). https://doi.org/10.1038/npp.2017.15
***Acknowledgement: This work was supported by São Paulo Research Foundation, Brazil (FAPESP; fellowships 2012/21387-8 and 2012/06123-4) for investigator LSBJ, R01MH084906 (BM), and a pilot fund from the Center for Evaluation of Nicotine in Cigarettes (NWS). The authors declare no conflict of interest.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]

===2012: [https://pubmed.ncbi.nlm.nih.gov/22503574/ The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition]===
*The e-cigarette can reduce desire to smoke and nicotine withdrawal symptoms 20 minutes after use.
*The nicotine content in this respect may be more important for males.
*The first study to demonstrate that the nicotine e-cigarette can improve working memory.
*[https://sci-hub.se/10.1016/j.addbeh.2012.03.004 PDF Version]
*Citation: Dawkins, L., Turner, J., Hasna, S., & Soar, K. (2012). The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition. Addictive Behaviors, 37(8), 970–973. doi:10.1016/j.addbeh.2012.03.004
*Electronic Cigarette Company (TECC) supplied the e-cigarettes and cartridges for this study. TECC had no involvement in the design or conduct of the study.

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated

===2003 [https://www.nature.com/articles/1300202 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects]===
*Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention.
*[https://www.nature.com/articles/1300202.pdf PDF Version]
*Citation: Mumenthaler, M., Yesavage, J., Taylor, J. et al. Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects. Neuropsychopharmacol 28, 1366–1373 (2003). doi: 10.1038/sj.npp.1300202
*Acknowledgements: This research was supported in part by NIMH Grant 40041; NIA Grant AG17824; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC); the Alcohol Beverage Medical Research Foundation; the Swiss Foundation for Alcohol Research; the Swiss National Science Foundation; and the Medical Research Service of the Department of Veterans Affairs.
*Keywords: cholinergic agents, ethanol, cognition, psychomotor performance, psychopharmacology, aerospace medicine

===1996 [https://link.springer.com/article/10.1007/BF02805972 Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers]===
*These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.
*Citation: Foulds, J., Stapleton, J., Swettenham, J. et al. Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacology 127, 31–38 (1996). https://doi.org/10.1007/BF02805972

===1994 [https://link.springer.com/article/10.1007/BF02245346 Smoking and raven IQ]===
*Nicotine has recently been shown to enhance measures of information processing speed including the decision time (DT) component of simple and choice reaction time and the string length measure of evoked potential waveform complexity. Both (DT and string length) have been previously demonstrated to correlate with performance on standard intelligence tests ([[Special:MyLanguage/Abbreviations|'''IQ''']]).
*In this experiment we used the Raven [[Special:MyLanguage/Abbreviations|'''Advanced Progressive Matrices (APM)''']] test. APM scores were significantly higher in the smoking session compared to the non-smoking session, suggesting that nicotine acts to enhance physiological processes underlying performance on intellectual tasks.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/BF02245346 PDF Version]
*Citation: Stough, C., Mangan, G., Bates, T. et al. Smoking and raven IQ. Psychopharmacology 116, 382–384 (1994). doi: 10.1007/BF02245346
*Key words: Intelligence, APM, Nicotine, Smoking Cholinergic system

===1992 [https://pubmed.ncbi.nlm.nih.gov/1579636/ Nicotine as a cognitive enhancer]===
*Nicotine improves attention in a wide variety of tasks in healthy volunteers.
*Nicotine improves immediate and longer term memory in healthy volunteers.
*Nicotine improves attention in patients with probable Alzheimer's Disease.
*While some of the memory effects of nicotine may be due to enhanced attention, others seem to be the result of improved consolidation as shown by post-trial dosing.
*[https://sci-hub.st/10.1016/0278-5846(92)90069-q PDF Version]
*Citation: Warburton DM. Nicotine as a cognitive enhancer. Prog Neuropsychopharmacol Biol Psychiatry. 1992 Mar;16(2):181-91. doi: 10.1016/0278-5846(92)90069-q. PMID: 1579636.
*Keywords: acetylcholine, Alzheimer's Disease, attention, cholinergic, memory, nicotine, scopolamine.
 

='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
*See Also: The Inflamation Section

===2025: [https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00167-8 Long COVID – a critical disruption of cholinergic neurotransmission?]===
*Conclusions: "A review of the literature indicates that a significant disruption of cholinergic neurotransmission might be a central issue for both LC/ME/CFS and PVS. The hypothesis of a viral blockade of nAChRs and the possibility of a competitive reversal of this blockade by LDTN has been corroborated by highly promising results in the broad application of this method to numerous patients. Randomized controlled trials are necessary to determine whether these preliminary results can be substantiated by evidence. However, LDTN application provides many patients with a method that offers a high probability of symptom relief with only minor side effects and represents an affordable therapeutic intervention for the majority of people affected worldwide. Furthermore, dose-finding studies are required to develop individually adapted therapy regimens with regard to dosage and duration of therapy."
*Citation: Leitzke, M., Roach, D.T., Hesse, S. et al. Long COVID – a critical disruption of cholinergic neurotransmission?. Bioelectron Med 11, 5 (2025). https://doi.org/10.1186/s42234-025-00167-8

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===
* States the obvious: the exposure (smoke vs. nicotine and dose need to be characterised correctly).
* Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.
* Salehi Z, Motlagh Ghoochani BFN, Hasani Nourian Y, Jamalkandi SA, Ghanei M. Allergy Asthma Clin Immunol. 2023 Jun 1;19(1):49. doi: 10.1186/s13223-023-00797-0. PMID: 37264452 Review.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36650574/ Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?] ===
* Nicotine COVID/SARS-CoV-2 interaction mystery takes another turn.
* Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh).
* We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.
*In all four of the cases we studied, transcutaneous use of nicotine led to a near immediate improvement in symptoms and rapid restitutio ad integrum. The course of symptom improvement was as distinct as the clinical presentation of post-COVID-19 syndrome in each patient.
*Citation: Leitzke M. Bioelectron Med. 2023 Jan 18;9(1):2. doi: 10.1186/s42234-023-00104-7. PMID: 36650574 Free PMC article.

===2023: [https://www.nature.com/articles/s41598-023-45072-9 Treatment of 95 post-Covid patients with SSRIs]===
*To stick nicotine patches helps PCS (post-COVID syndrome) patients. This may be not only because nicotine is a nicotinic receptor agonist and therefore an opponent of these poisonous metabolites, but nicotine is a strong acetylcholine (ACh) agonist as well.
*Citation: Rus, C.P., de Vries, B.E.K., de Vries, I.E.J. et al. Treatment of 95 post-Covid patients with SSRIs. Sci Rep 13, 18599 (2023). https://doi.org/10.1038/s41598-023-45072-9

===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183099/ Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials]===
* Studies show that the penetration of SARS-CoV-2 into upper respiratory tract, bronchial and pulmonary cells involve transmembrane receptor ACE2, which probably interacts with acetylcholine nicotinic receptors of the α7 subtype. The mechanism of the interactions remains hypothetical.
* Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
* Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.
* Excessive secondary cytokine reaction plays a role in the mortality associated with COVID. One of the hypotheses to explain the effect of nicotine on the occurrence of severe forms of COVID and death is based on the loss of the downregulation of the parasympathetic nervous system, which exerts an inhibitory effect on cytokine storm, especially in the lung and digestive tract. The α 7-type nicotinic receptors are part of this chain of reaction.
* B. Dautzenberg, A. Levi, M. Adler, and R. Gaillardc. Respir Med Res. 2021 Nov; 80: 100844. Published online 2021 Jun 7. doi: 10.1016/j.resmer.2021.100844 PMCID: PMC8183099 PMID: 34153704

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
*Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
*Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.

===2020: [https://www.sciencedirect.com/science/article/pii/S2214750020302924 Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system]===
*Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.
*Citation: Farsalinos K, Niaura R, Le Houezec J, Barbouni A, Tsatsakis A, Kouretas D, Vantarakis A, Poulas K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep. 2020 Apr 30;7:658-663. doi: 10.1016/j.toxrep.2020.04.012. PMID: 32355638; PMCID: PMC7192087.

=== 2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679833/ Mitochondria as a possible target for nicotine action] ===

* See also this twitter thread for detailed information on possible mechanisms. https://x.com/angryhacademic/status/1741968457296490977?s=20
* This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design.
* The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.
* J Bioenerg Biomembr. 2019; 51(4): 259–276. Published online 2019 Jun 13. doi: 10.1007/s10863-019-09800-z PMCID: PMC6679833 PMID: 31197632

='''Digestive Tract / Bowel'''=
===2024: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntae193/7727428 The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis]===
*"Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients."
**Citation: Kastratovic N, Markovic V, Arsenijevic A, Volarevic A, Zdravkovic N, Zdravkovic M, Brankovic M, Gmizic T, Harrell CR, Jakovljevic V, Djonov V, Volarevic V. The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis. Nicotine Tob Res. 2024 Aug 5:ntae193. doi: 10.1093/ntr/ntae193. Epub ahead of print. PMID: 39101540.
***Paywalled, unable to view funding/COI

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S000927971931734X Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model]===
*Animal study
*Conclusion: "Taken together, we demonstrated that nicotine inhibits apoptosis and proliferation by modulating AMPK/mTOR pathway-mediated autophagy and improves colitis severity in the DSS-induced UC mouse model. These findings provide new insights into the mechanism of nicotine treatment on UC autophagy. Further exploration of the mechanism of nicotine in autophagy and targeting factors might be considered a new approach for ulcerative colitis treatment."
*[https://sci-hub.st/10.1016/j.cbi.2020.108943 PDF Full paper]
**Citation: Gao Q, Bi P, Luo D, Guan Y, Zeng W, Xiang H, Mi Q, Yang G, Li X, Yang B. Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model. Chem Biol Interact. 2020 Feb 1;317:108943. doi: 10.1016/j.cbi.2020.108943. Epub 2020 Jan 10. PMID: 31926917.
***Acknowledgement: This work was supported by the Yunnan Key Laboratory of Tobacco Chemistry Project [Grant No. 2017539200340397].

===2018 [https://academic.oup.com/jleukbio/article-abstract/104/5/1013/6935503 Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment]===
*Animal/Cell study
*These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM-1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC.
*[https://sci-hub.st/10.1002/JLB.3A0717-304R PDF Full paper]
**Citation: Maruta K, Watanabe C, Hozumi H, Kurihara C, Furuhashi H, Takajo T, Okada Y, Shirakabe K, Higashiyama M, Komoto S, Tomita K, Nagao S, Ishizuka T, Miura S, Hokari R. Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. J Leukoc Biol. 2018 Nov;104(5):1013-1022. doi: 10.1002/JLB.3A0717-304R. Epub 2018 Jun 14. PMID: 29901817.
***Acknowledgement: This research was supported by grants from the National Defense Medical College, by Grants-in-aid for the Intractable Diseases Project of the Ministry of Health, Labour, and Welfare of Japan, and by Grantsin-aid for Scientific Research from the Japanese Ministry of Education (2646080).

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533410/ Novel Insights on the Effect of Nicotine in a Murine Colitis Model]===
*Animal study
*Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-α.
**Citation: AlSharari SD, Akbarali HI, Abdullah RA, Shahab O, Auttachoat W, Ferreira GA, White KL, Lichtman AH, Cabral GA, Damaj MI. Novel insights on the effect of nicotine in a murine colitis model. J Pharmacol Exp Ther. 2013 Jan;344(1):207-17. doi: 10.1124/jpet.112.198796. Epub 2012 Oct 31. PMID: 23115221; PMCID: PMC3533410.
***Acknowledgement: This work was supported by National Institutes of Health [Grants DA-019377; (to M.I.D.) and DK 046367] (to H.I.A.).

===2012 [https://journals.physiology.org/doi/full/10.1152/ajpgi.00411.2011 Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation]===
*Animal study
*"In summary, in an acute and postinflammatory model of colitis, we demonstrated that nAChRs mediate suppression of hyperexcitability of colonic sensory. The present study also highlights the potential of in vivo treatment with nicotine towards its antinociceptive effects in colonic inflammation."
**Citation: Abdrakhmanova GR, Kang M, Imad Damaj M, Akbarali HI. Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G740-7. doi: 10.1152/ajpgi.00411.2011. Epub 2012 Jan 12. PMID: 22241859; PMCID: PMC3330777."
***Acknowledgement: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-046367 (to H. I. Akbarali).

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2008 [https://www.hindawi.com/journals/grp/2008/237185/ Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study]===
*Smoking has a detrimental effect in [[Special:MyLanguage/Abbreviations|'''Crohn's disease (CD)''']], but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits [[Special:MyLanguage/Abbreviations|'''ulcerative colitis (UC)''']], and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis.
*In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.
*[http://downloads.hindawi.com/journals/grp/2008/237185.pdf PDF Version]
**Citation: J. R. Ingram, J. Rhodes, B. K. Evans, and G. A. O. Thomas, Hindawi Publishing Corporation, Gastroenterology Research and Practice, Volume 2008, Article ID 237185, 6 pages, doi:10.1155/2008/237185
***Acknowledgements: J. R. Ingram was supported by the Gastrointestinal Foundation Trust. SLA Pharma gave financial support to the project. The authors are indebted to Dr. J. T. Green (of Cardiff and Vale Hospitals Trust) who referred patients, and to Professor G. T. Williams (GTW) who performed all histological assessments.

===2004 [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full Transdermal nicotine for induction of remission in ulcerative colitis]===
*Ulcerative colitis is largely a disease of nonsmokers and patients who have quit smoking. Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis.
*[https://sci-hub.st/https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full PDF Version]
**Citation: McGrath, J., McDonald, J. W., & MacDonald, J. K. (2004). Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004722.pub2
***Acknowledgements: Funding for the IBD/FBD Review Group (October 1, 2005 - September 30, 2010) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch; the Canadian Agency for Drugs and Technologies in Health (CADTH); and the CIHR Institutes of Health Services and Policy Research; Musculoskeletal Health and Arthritis; Gender and Health; Human Development, Child and Youth Health; Nutrition, Metabolism and Diabetes; and Infection and Immunity. Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12072594/ Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice]===
*Animal Study
*Conclusions: (1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides.
*[https://sci-hub.st/10.1097/00042737-200206000-00005 PDF of full paper]
**Citation: Eliakim R, Fan QX, Babyatsky MW. Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice. Eur J Gastroenterol Hepatol. 2002 Jun;14(6):607-14. doi: 10.1097/00042737-200206000-00005. PMID: 12072594.

===1999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/ Nicotine treatment for ulcerative colitis]===
*No withdrawal symptoms suggesting nicotine addiction have been reported either after 4–6 weeks of therapy in short-term studies, or after a period of up to 6 months in the only long-term study available
*It can be concluded from these data that transdermal nicotine alone has limited efficacy in active ulcerative colitis and is ineffective as maintenance treatment. On the other hand, if administered in combination with mesalazine, nicotine is superior to placebo in promoting clinical remission of ulcerative colitis of mild to moderate degree, may represent an efficacious alternative to steroids in selected cases and, when effective, seems to exert a longer-lasting therapeutic effect than prednisone.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/pdf/bcp0048-0481.pdf PDF Version]
**Citation: Guslandi M. Nicotine treatment for ulcerative colitis. Br J Clin Pharmacol. 1999 Oct;48(4):481-4. doi: 10.1046/j.1365-2125.1999.00039.x. PMID: 10583016; PMCID: PMC2014383.
***No funding/COI information

===1996 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398677/ The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.]===
*Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial deterrent of UC and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.
*[https://sci-hub.st/10.1136/pgmj.72.854.714 PDF Version]
**Citation: Birtwistle J. The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis. Postgrad Med J. 1996 Dec;72(854):714-8. doi: 10.1136/pgmj.72.854.714. PMID: 9015463; PMCID: PMC2398677.

===1996: [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of ulcerative colitis.
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1994: [https://pubmed.ncbi.nlm.nih.gov/8114833/ Transdermal nicotine for active ulcerative colitis]===
*The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.
**Citation: Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994 Mar 24;330(12):811-5. doi: 10.1056/NEJM199403243301202. PMID: 8114833.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against ulcerative colitis (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Down's Syndrome'''=
===2001: [https://link.springer.com/chapter/10.1007/978-3-7091-6262-0_19 Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome]===
*To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5–31 years) received placebo and a single dose of transdermal nicotine (5mg patch) over 2h in a single-blind, within-subjects repeated measures design.
*Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.
*Citation: Bernert G., Sustrova M., Sovcikova E., Seidl R., Lubec G. (2001) Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. In: Lubec G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_19

===2000 [https://pubmed.ncbi.nlm.nih.gov/11052587/ Effects of transdermal nicotine on cognitive performance in Down's syndrome]===
*We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalizable because of small numbers.
*[https://sci-hub.st/10.1016/S0140-6736(00)02848-8 PDF Version]
*Seidl R, Tiefenthaler M, Hauser E, Lubec G. Effects of transdermal nicotine on cognitive performance in Down's syndrome. Lancet. 2000 Oct 21;356(9239):1409-10. doi: 10.1016/S0140-6736(00)02848-8. PMID: 11052587.
*Acknowledgements: We thank Pharmacia-Upjohn, Uppsala, Sweden, for providing transdermal nicotine patches. This study was supported by the Red Bull Company, Salzburg.
 

='''Dyskinesia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
*In summary, our data show that nicotine treatment decreases haloperidol-induced VCMs [vacuous chewing movements] in an established rat model of tardive dyskinesia. The demonstration that nicotine removal leads to a return of VCMs, whereas nicotine re-exposure reduced haloperidol-induced VCMs, suggests a causal relationship. These data have clinical applications for the treatment of tardive dyskinesias associated with long-term antipsychotic treatment using nicotine.
**Citation: Bordia T, McIntosh JM, Quik M. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. J Pharmacol Exp Ther. 2012 Mar;340(3):612-9. doi: 10.1124/jpet.111.189100. Epub 2011 Dec 5. PMID: 22144565; PMCID: PMC3286320.
***Acknowledgement: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS47162, NS59910]; and the National Institutes of Health National Institute of Mental Health [Grant MH53631]
 

='''Dystonia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

='''Endurance / Exercise / Athletic Performance'''=

===2024 Article: [https://web.archive.org/web/20241002001111/https://www.golfdigest.com/story/tour-pros-little-helper-does-nicotine-create-a-competitive-advantage Tour Pro’s Little Helper: Does nicotine create a competitive advantage?]===
*"In all, we talked to nearly 100 pro golfers to learn more about the popularity and usage patterns of nicotine on the major professional tours. Some told us they turn to tobacco or nicotine products for an energy boost; others say it helps them concentrate or feel relaxed. But for many, it’s just about keeping on."

===2023 [https://www.mdpi.com/1660-4601/20/2/1009 The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study]===
*The lower perception of pain intensity that we reported after the 8 mg nicotine dose application might be an important factor that affects performance. However, we did not report any improvement in physical performance parameters.
**Citation: Bartík P, Šagát P, Pyšná J, Pyšný L, Suchý J, Trubák Z, Petrů D. The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study. Int J Environ Res Public Health. 2023 Jan 5;20(2):1009. doi: 10.3390/ijerph20021009. PMID: 36673765; PMCID: PMC9859273.
***Acknowledgement: The authors would like to acknowledge the support of Prince Sultan University for paying the article processing charges (APC) of this publication. This study was conducted by the SSDRL research group.

===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745004/ Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players]===
*Our HRV and salivary analysis revealed that nicotine could induce endocrine and sympathetic nerve activity in healthy male baseball players who had never smoked. Compared with the placebo group, the nicotine group exhibited enhanced cognitive function (an average decrease in motor reaction time of 11.14%; an average decrease in motor reaction time of 5.72%) and baseball-hitting performance (an average increase of 34.69%), and small effect sizes were observed for these results. However, muscle strength did not increase after nicotine intake.
**Citation: Fang SH, Lu CC, Lin HW, Kuo KC, Sun CY, Chen YY, Chang WD. Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players. Int J Environ Res Public Health. 2022 Jan 4;19(1):515. doi: 10.3390/ijerph19010515. PMID: 35010774; PMCID: PMC8745004.
***Acknowledgement: Study was supported by the Ministry of Science and Technology in Taiwan (No: MOST 107-2410-H-028-002-MY2 and MOST 109-2410-H-028-009-MY3).

===2022 [https://www.tandfonline.com/doi/full/10.1186/s12970-021-00413-9 Nicotine supplementation enhances simulated game performance of archery athletes]===
*In summary, these results indicated that 2-mg nicotine gum supplementation enhanced cognitive function, decreased saliva α-amylase activity and HRV through stimulating the sympathetic adrenergic system. More importantly, the archery scores were significantly increased after nicotine supplementation.
**Citation: Hung BL, Chen LJ, Chen YY, Ou JB, Fang SH. Nicotine supplementation enhances simulated game performance of archery athletes. J Int Soc Sports Nutr. 2021 Feb 18;18(1):16. doi: 10.1186/s12970-021-00413-9. PMID: 33602279; PMCID: PMC7890628.
***Acknowledgement: Funded by the Taiwan Ministry of Science and Technology (MOST104–2628-H-028-001-MY2).

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236038/ A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males]===
*The present study has demonstrated that low-dose (2 mg) nicotine gum increases leg extensor torque, but counter-movement jump and anaerobic capacity during WAnT remained unchanged when compared to a placebo, whilst there were minimal effects of the 4-mg nicotine gum on the performance parameters measured. Together with our previous observation [24], these results indicate that nicotine per se can improve exercise endurance and muscular strength, something that WADA should continue to monitor alongside patterns of (mis)use.
**Citation: Mündel T, Machal M, Cochrane DJ, Barnes MJ. A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males. Sports Med Open. 2017 Dec;3(1):5. doi: 10.1186/s40798-016-0074-8. Epub 2017 Jan 13. PMID: 28092056; PMCID: PMC5236038.
***Acknowledgement: This study was funded in part by a grant from the World Anti-Doping Agency.

===2006 [https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2006.033373 Effect of transdermal nicotine administration on exercise endurance in men]===
*Nicotine improved exercise endurance by 17 ± 7%, and in the absence of any effect on the usual peripheral markers, such as ventilation, heart rate and blood metabolites, we conclude that nicotine prolongs endurance by a central mechanism that may involve nicotinic receptor activation and/or altered activity of dopaminergic pathways.
*[https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2006.033373 PDF Version]
**Citation: Mündel T, Jones DA. Effect of transdermal nicotine administration on exercise endurance in men. Exp Physiol. 2006 Jul;91(4):705-13. doi: 10.1113/expphysiol.2006.033373. Epub 2006 Apr 20. PMID: 16627574.
 

='''Eyes - Ocular - Vision'''=
==Myopia (short-sighted, near-sighted)==
===2024 [https://iovs.arvojournals.org/article.aspx?articleid=2800816 Administration of Nicotine Can Inhibit Myopic Growth in Animal Models]===
*Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia.
**Citation: Thomson K, Karouta C, Ashby R. Administration of Nicotine Can Inhibit Myopic Growth in Animal Models. Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):29. doi: 10.1167/iovs.65.11.29. PMID: 39292451; PMCID: PMC11412605.
***Acknowledgement: Funded by ANU Connect Ventures through a Discovery Translation Fund grant (Project ID: DTF311).
 

='''Hashimoto's disease (Hashimoto thyroiditis)'''=
*[https://www.hopkinsmedicine.org/health/conditions-and-diseases/hashimotos-thyroiditis Hashimoto's Thyroiditis] "is when your thyroid gland becomes irritated or inflamed. Hashimoto thyroiditis is the most common type of this health problem. It may also be called chronic autoimmune thyroiditis. This thyroiditis is an autoimmune disease. It occurs when your body makes antibodies that attack the cells in your thyroid. The thyroid gland becomes overrun with white blood cells and becomes scarred. This makes the gland feel firm and rubbery. The thyroid then can’t make enough of the thyroid hormone."

===2020: [https://www.endocrine-abstracts.org/ea/0070/ea0070oc8.4?_ga=2.114580999.1434360570.1735281186-102848752.1735281184 Cigarette smoking and the risk to develop symptoms of Hashimoto’s thyroiditis]===
*"In patients who had discontinued smoking at the age of 39 years or more, the diagnosis of HT was predominantly made after the discontinuation of smoking."

===2013: [https://onlinelibrary.wiley.com/doi/10.1111/cen.12222 Smoking and thyroid]===
*"Smoking has distinct associations with thyroid function and size in healthy subjects. It has remarkable and contrasting associations with thyroid function in autoimmune thyroid disease (lower risk of Hashimoto's disease and higher risk of Graves’ disease) and with thyroid size in nodular disease (lower risk of thyroid carcinoma and higher risk of nontoxic goitre and multinodularity). The observed associations likely indicate causal relationships in view of consistent associations across studies, the presence of a dose–response relationship and disappearance of the associations after cessation of smoking. Which mechanisms mediate the many effects of smoking remains largely obscure. Probably, they differ between the various effects. The divergent effects of smoking on the expression of autoimmune thyroid disease are intriguing and reminiscent on the contrasting effects of smoking on inflammatory bowel disease: protective against ulcerative colitis (OR 0·41, 0·34–0·48) but risky for Crohn's disease (OR 1·61, 1·27–2·03)."
*[https://sci-hub.st/10.1111/cen.12222 PDF Full paper]
**Citation: Wiersinga, W. M. (2013). Smoking and thyroid. Clinical Endocrinology, 79(2), 145–151. doi:10.1111/cen.12222
***Acknowledgement: None stated

='''HIV (human immunodeficiency virus)'''=

===2025: [https://www.sciencedirect.com/science/article/abs/pii/S0149763425003495 Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential]===
*"Approximately half of people with HIV (PWH) experience neurocognitive impairment (NCI), despite antiretroviral therapies that have turned what was formerly a death sentence to a chronic illness. No targeted treatments exist for HIV-associated NCI, impacting long-term quality of life. Smoking rates in PWH are nearly double those of the general population, and with evidence for pro-cognitive effects of nicotine, this may reflect self-medication. However, clinical studies yield inconsistent findings-some showing benefits, others reporting harm-likely due to variability in nicotine exposure methods, cognitive testing paradigms, withdrawal states, and confounding comorbidities. In contrast, animal studies offer a more controlled framework to isolate the effects of nicotine. Preclinical models suggest that nicotine may mitigate HIV-associated cognitive deficits by acting on α7 nicotinic acetylcholine receptors (nAChRs), leading to reduced neuroinflammation. These findings highlight the therapeutic potential of targeting nAChRs, though mechanisms remain incompletely understood..."
**Citation: Jha NA, Ayoub SM, Brody AL, Young JW. Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential. Neurosci Biobehav Rev. 2025 Aug 23;177:106348. doi: 10.1016/j.neubiorev.2025.106348. Epub ahead of print. PMID: 40854454.
***Acknowledgement: This work was supported by the National Institutes of Health [grant numbers: R01MH134175 (JWY), R01MH128869 (JWY), R01DA051295 (JWY)]...

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

='''Huntington’s Disease'''=

===2005: [https://pubmed.ncbi.nlm.nih.gov/16140176/ Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats]===
*These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.
*In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.
*[https://sci-hub.se/10.1016/j.brainresbull.2005.06.024 PDF Version]
**Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.
 

='''Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis''' (See Also: Allergies/Hayfever/Histamines)=
*[https://www.nhlbi.nih.gov/health/hypersensitivity-pneumonitis Hypersensitivity pneumonitis] is a rare immune system disorder that affects the lungs. This disease is also called bird or pigeon fancier’s lung, farmer’s lung, hot tub lung, cheese worker's lung, Bagassosis, mushroom worker's lung, malt worker's lung, or humidifier lung.
*[https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity pneumonitis] (HP) classified as an interstitial lung disease is characterized by a complex immunological reaction of the lung parenchyma in response to repetitive inhalation of a sensitized allergen.

===2023: [https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity Pneumonitis]===
*Cigarette smoking seems to protect from developing clinically significant HP likely due to nicotine inhibiting macrophage activation and lymphocyte proliferation.
*However, smokers who develop HP have been shown to have a more severe course and higher mortality.
**Citation: Chandra D, Cherian SV. Hypersensitivity Pneumonitis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499918/

===2007: [https://academic.oup.com/qjmed/article-abstract/100/4/233/2258683?redirectedFrom=fulltext Extrinsic allergic alveolitis: incidence and mortality in the general population]===
*We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at ∼0.9 cases per 100 000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39–0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05–4.33).
**Citation: M. Solaymani-Dodaran, J. West, C. Smith, R. Hubbard, Extrinsic allergic alveolitis: incidence and mortality in the general population, QJM: An International Journal of Medicine, Volume 100, Issue 4, April 2007, Pages 233–237, https://doi.org/10.1093/qjmed/hcm008

===2002: [https://www.atsjournals.org/doi/10.1164/rccm.200210-1154OC Inhibitory Effect of Nicotine on Experimental Hypersensitivity Pneumonitis In Vivo and In Vitro]===
*Animal study
*Results of this study show that nicotine reduces the alveolar inflammatory response to S. rectivirgula antigen and affects some AM (stimulated with LPS or S. rectivirgula) functions in vitro. This influence could be, at least in part, responsible for the protection that smokers have against development of HP. Because nicotine is effective in the treatment of ulcerative colitis, it could also be of interest in the treatment of HP and other pulmonary inflammatory diseases.
**Citation: Blanchet MR, Israël-Assayag E, Cormier Y. Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med. 2004 Apr 15;169(8):903-9. doi: 10.1164/rccm.200210-1154OC. Epub 2003 Dec 30. PMID: 14701707.

===1992: [https://pubmed.ncbi.nlm.nih.gov/1344064/ Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum]===
*It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.
**Citation: Arima K, Ando M, Ito K, Sakata T, Yamaguchi T, Araki S, Futatsuka M. Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum. Arch Environ Health. 1992 Jul-Aug;47(4):274-8. doi: 10.1080/00039896.1992.9938361. PMID: 1344064.

===1987: [https://pubmed.ncbi.nlm.nih.gov/3499342/ Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking]===
*Farmer's lung was only slightly more common among atopic than among non-atopic subjects and twice as common among non-smokers as among smokers.
**Citation: Terho EO, Husman K, Vohlonen I. Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking. Eur J Respir Dis Suppl. 1987;152:19-28. PMID: 3499342.

===1977: [https://pmc.ncbi.nlm.nih.gov/articles/PMC470791/ Extrinsic allergic alveolitis: a disease commoner in non-smokers.]===
*In the literature of extrinsic allergic alveolitis non-smokers predominate in those papers in which smoking habits are recorded (Hapke et al., 1968; Schlueter et al., 1969; Schofield et al., 1976). Studies of the prevalence of precipitating antibodies against Micropolyspora faeni in farmers have shown that they are detected significantly more often in non-smokers than in smokers (Morgan et al., 1975).
**Citation: Warren CP. Extrinsic allergic alveolitis: a disease commoner in non-smokers. Thorax. 1977 Oct;32(5):567-9. doi: 10.1136/thx.32.5.567. PMID: 594937; PMCID: PMC470791.
 

='''Hypothyroidism'''=

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated
 

='''Inflammation'''=

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871277/ Effect of Nicotine on Immune System Function]===
*Despite the completely destructive and harmful effects of cigarette smoke, nicotine via stimulation of the α7 receptor can promote the anti-inflammatory benefits on the immune system. However, these effects depend on the concentration, and administration methods are different and sometimes contradictory. It can be used successfully to treat or inhibit autoimmune diseases. Although the exact mechanism of this treatment is unknown, it appears to involve inhibiting downstream intracellular pathways that lead to the secretion of pre-inflammatory cytokines.
**Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
**Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483
***Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
**Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.
***Acknowledgement: All authors have declared that no financial support was received from any organization for the submitted work.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
**Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.
***Acknowledgement: This work was supported by University of Castilla-La Mancha Research Programme 2020-GRIN-28705.

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila and Chlamydia pneumonia infection...
**Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2011 [https://pubmed.ncbi.nlm.nih.gov/21691078/ Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells]===
*In summary, we showed that nicotine could suppress TNF-α expression mainly through activation of the α7 nAChR subunit, which inhibited the MyD88/IκBα/NFκB signaling pathway in HBE16 airway epithelial cells. These findings may provide new information on the potential pharmacological effects of nicotine and nAChR in the treatment of respiratory inflammatory diseases. Further research on nicotine and nAChRs may provide more evidence for the treatment of inflammatory diseases and the development of related drugs.
*[https://www.karger.com/Article/Pdf/329982 PDF Version]
**Citation: Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982
***Acknowledgement: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
**Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
***Acknowledgement: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.

===2008 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693390/ Neuronal Nicotinic Alpha7 Receptors Modulate Inflammatory Cytokine Production in the Skin Following Ultraviolet Radiation]===
*Animal study
*Cytokine responses to UV in mice administered chronic oral nicotine, a nAChR agonist, were reduced... These results demonstrate that nAChRα7 can participate in modulating a local pro-inflammatory response in the absence of parasympathetic innervation.
**Citation: Osborne-Hereford AV, Rogers SW, Gahring LC. Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation. J Neuroimmunol. 2008 Jan;193(1-2):130-9. doi: 10.1016/j.jneuroim.2007.10.029. PMID: 18077004; PMCID: PMC2693390.
***Acknowledgement: These studies were funded by NIH grants DA015148 and DA018930 (LCG), PO1 HL72903 (LCG, SWR) and the Browning Foundation of Utah.

===2006 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809735/ Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7]===
*Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-α, prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-1α and MIP-1α, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet’s disease and Crohn’s disease. In addition, the nicotinic acetylcholine receptor-α7 (α7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the α7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes.
*These suppressive effects of nicotine were caused at the transcriptional level and were mediated through α7nAChR. Nicotine suppressed the phosphorylation of I-κB, and then inhibited the transcriptional activity of nuclear factor-κB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.
*This supports the therapeutic use of nicotine in some inflammatory diseases; the NF-κB activation pathway is one of the most critical molecular targets of nicotine therapy.
**Citation: Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. 2006 Oct;146(1):116-23. doi: 10.1111/j.1365-2249.2006.03169.x. PMID: 16968406; PMCID: PMC1809735.
 

='''Legionella Pneumophila (Legionnaires' disease)'''=

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''ME/CFS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome'''=
*See Also: COVID (Long COVID)
 

='''Mental Health'''=
*See subcategories below
 
=='''Mental Health - Anxiety'''==
===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated
 

=='''Mental Health - Behavior Issues'''==
*See Also: ADD/ADHD above

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0028390819305003?via%3Dihub Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies]===
*Human and Animal Studies
*Clinical trials and case series report anti-aggressive effects of nicotine. Here we argue that the [[Special:MyLanguage/Abbreviations|'''nAChR''']] system, the molecular basis for the global public health problem of tobacco smoking, may also be a key target for modulation of aggressive behaviors. Future research should aim to clarify which forms of aggression are most strongly affected by nAChR modulation, identify the nAChR subtypes, circuits, and neurobiological mechanisms of nicotine action, and determine whether more selective nAChR-active agents can replicate or improve the serenic effects of nicotine, especially with chronic dosing. Given the prevalence of aggressive behaviors across neuropsychiatric disorders affecting the very young to the very old, these studies have the potential to have a significant impact on public health.
*[https://sci-hub.st/https://doi.org/10.1016/j.neuropharm.2019.107929 PDF Version]
*Citation: Alan S. Lewis, Marina R. Picciotto, Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies, Neuropharmacology, Volume 167, 2020, 107929, ISSN 0028-3908, doi: 10.1016/j.neuropharm.2019.107929.
*Acknowledgements: This work was supported by National Institutes of Health grants MH116339 (A.S.L.), MH077681 and DA14241 (M.R.P.).

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
*Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
*Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).
 

=='''Mental Health - Depression'''==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15950 The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study]===
*In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.
*Citation: Yebo Yu, Fan Yang, Mingqi Fu, Farooq Ahmed, Muhammad Shahid, Jing Guo, Relationship Between Work-Family Conflict and Depressive Symptoms Among Male Firefighters in China, Journal of Occupational & Environmental Medicine, 10.1097/JOM.0000000000002759, 65, 4, (337-343), (2022).

===2021 [https://www.sciencedirect.com/science/article/abs/pii/S0376871621005676 Adolescent depression symptoms and e-cigarette progression]===
*Depression symptoms predicted more rapid e-cigarette progression in adolescents.
*E-cigarette use was not associated with an escalation in depression symptoms.
*E-cigarette use was not related to the development of depression symptoms over time.
*Must pay to view PDF
*Citation: Afaf F. Moustafa, Shannon Testa, Daniel Rodriguez, Stephen Pianin, Janet Audrain-McGovern, Adolescent depression symptoms and e-cigarette progression, Drug and Alcohol Dependence, Volume 228, 2021, 109072, ISSN 0376-8716, doi.org/10.1016/j.drugalcdep.2021.109072.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2000 [https://www.sciencedirect.com/science/article/abs/pii/S0091305700002057 The Effects of Nicotine on Neural Pathways Implicated in Depression: A Factor in Nicotine Addiction?]===
*It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine.
*[https://sci-hub.st/10.1016/S0091-3057(00)00205-7 PDF Version]
*Citation: Balfour, D. J. ., & Ridley, D. L. (2000). The Effects of Nicotine on Neural Pathways Implicated in Depression. Pharmacology Biochemistry and Behavior, 66(1), 79–85. doi:10.1016/s0091-3057(00)00205-7

===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0149763417301793 Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression]===
*Nicotine improves cognitive performance in clinical and preclinical studies.
*Nicotine may also benefit depressive symptoms and depressive behavior.
*Cognitive and mood benefits may be mediated by nicotinic effect on neural networks.
*Nicotine’s effects on networks may reverse network changes seen in depression.
*Improvement to mood and cognition may particularly benefit older depressed adults.
*Both preclinical and clinical studies support that nicotine and other nAChR agonists can improve depressive behavior, mood, and cognitive performance. nAChR agonists also demonstrate neuropharmacologic effects that oppose the intrinsic network alterations reported in MDD. Through modulation of intrinsic functional networks, nAChR agonists may reduce depressive symptoms, enhance emotional regulation ability, and improve cognitive deficits common in LLD. For these reasons, we propose nAChR agonists as a potential novel treatment for the mood and cognitive symptoms of LLD.
*[https://sci-hub.st/10.1016/j.neubiorev.2017.08.018 PDF Version]
*Citation: Gandelman, J. A., Newhouse, P., & Taylor, W. D. (2018). Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression. Neuroscience & Biobehavioral Reviews, 84, 289–298. doi:10.1016/j.neubiorev.2017.08.0
*Acknowledgement: Supported by NIH grants K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences.

===2018 [https://pubmed.ncbi.nlm.nih.gov/29795403/ Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder]===
*In [[Special:MyLanguage/Abbreviations|'''MDD''']], acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD.
*[https://sci-hub.st/10.1038/s41386-018-0069-x PDF Version]
*Citation: Janes AC, Zegel M, Ohashi K, Betts J, Molokotos E, Olson D, Moran L, Pizzagalli DA. Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. Neuropsychopharmacology. 2018 Nov;43(12):2445-2451. doi: 10.1038/s41386-018-0069-x. Epub 2018 Apr 19. PMID: 29795403; PMCID: PMC6180119.
*Acknoledgements: This project was supported by the National Institute on Drug Abuse grants K10 DA029645 and K02 DA042987 (ACJ). DAP was partially supported by National Institute of Mental Health grant R37 MH068376. Over the past 3 years, DAP has received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Pfizer and Posit Science, for activities unrelated to the current research.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/ Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Non-Smokers with Late-Life Depression]===
*[[Special:MyLanguage/Abbreviations|Late '''Life Depression (LLD)''']] is characterized by poor antidepressant response and cognitive dysfunction. Late life depression has no currently approved treatment that improves both its mood and cognitive symptoms.
*We observed robust response (86.7%) and remission rates (53.3%). There was a significant decrease in MADRS (Montgomery-Asberg Depression Rating scale) over the study, with improvement seen as early as three weeks. We also observed improvement in apathy and rumination. We did not observe improvement on the CPT (Conners Continuous Performance Test), but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/pdf/nihms965043.pdf PDF Version]
*Citation: Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137. PMID: 30192444; PMCID: PMC6129985.
*Acknowledgements: This research was supported by NIH grant K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. The sponsor provided funding for the study but did not influence the design or conduct of the study.

===2006 [https://pubmed.ncbi.nlm.nih.gov/16977477/ Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial]===
*These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
*[https://sci-hub.st/10.1007/s00213-006-0516-y PDF Version]
*Citation: McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2006 Nov;189(1):125-33. doi: 10.1007/s00213-006-0516-y. Epub 2006 Sep 15. PMID: 16977477.
*Acknowledgement: This research was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Dr. Rose is an inventor named on several nicotine patch patents and receives royalties from sales of certain nicotine patches.

===2002 [https://pubmed.ncbi.nlm.nih.gov/11995405/ Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients]===
*Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration.
*Citation: Salin-Pascual RJ. Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Rev Invest Clin. 2002 Jan-Feb;54(1):36-40. PMID: 11995405.

===1999 [https://link.springer.com/article/10.1007/s002130050879 Antidepressant effects of nicotine in an animal model of depression]===
*Animal Study
*Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals.
*The data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the [[Special:MyLanguage/Abbreviations|'''FSL''']] rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
*[https://sci-hub.st/https://doi.org/10.1007/s002130050879 PDF Version]
*Citation: Tizabi, Y., Overstreet, D., Rezvani, A. et al. Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142, 193–199 (1999). https://doi.org/10.1007/s002130050879
*Acknowledgements This work was supported in part by the Department of Pharmacology, Howard University, VAMC and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
*Keywords: Key words Nicotine · Nicotinic receptor · FSL and FRL rats · Animal model of depression

===1998 [https://pubmed.ncbi.nlm.nih.gov/9592048/ A novel effect of nicotine on mood and sleep in major depression]===
*Transdermal nicotine patches increased REM sleep in normal volunteers and depressed patients during 4 days of continuous administration. In addition, a significant improvement of mood was observed in depressed patients. Nicotinic mechanisms may be involved in depression. These findings suggest that nicotine receptor activation may be important in major depression and shows for the first time that nicotine patches may be useful in the treatment of depression.
*[https://sci-hub.st/10.1097/00001756-199801050-00012 PDF Version]
*Salín-Pascual RJ, Drucker-Colín R. A novel effect of nicotine on mood and sleep in major depression. Neuroreport. 1998 Jan 5;9(1):57-60. doi: 10.1097/00001756-199801050-00012. PMID: 9592048.
*ACKNOWLEDGEMENT: This work has been supported by the following grants: DGAPA-UNAM IN -200895 to R.J.S-P.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9746444/ Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression]===
*A high frequency of cigarette smoking has been reported among individuals with major depression.
*Results of the visual analog scale and [[Special:MyLanguage/Abbreviations|'''HAM-D''']] showed a significant improvement in depression after the second day of nicotine patches.
*Citation: Salín-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL, Delgado-Parra V. Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry. 1996 Sep;57(9):387-9. PMID: 9746444.

===1996 [https://psycnet.apa.org/record/1996-00468-019 Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.]===
*Depressed smokers relapsed significantly earlier than the nondepressed. Nicotine gum was significantly more effective than placebo gum among all smokers. The benefits of nicotine gum were particularly apparent among the depressed. Only 12.5% of depressed smokers quit successfully with placebo gum for 3 months, whereas 29.5% quit with nicotine gum. Depressed smokers reported more stress, less coping resources, more physical and psychological symptoms, and more frequent smoking in the presence of negative affect than did the nondepressed.
*[https://sci-hub.st/10.1037/0022-006X.64.4.791 PDF Version]
**Citation: Kinnunen, T., Doherty, K., Militello, F. S., & Garvey, A. J. (1996). Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement. Journal of Consulting and Clinical Psychology, 64(4), 791–798. https://doi.org/10.1037/0022-006X.64.4.791

===1995 [https://pubmed.ncbi.nlm.nih.gov/8619011/ Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients]===
*The main finding of the present study was that nicotine patches induced an increase in REM sleep time in depressed patients without any other changes in sleep variables
*[https://sci-hub.st/10.1007/BF02246496 PDF Version]
*Citation: Salín-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colín R. Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology (Berl). 1995 Oct;121(4):476-9. doi: 10.1007/BF02246496. PMID: 8619011.
*Acknowledgement: This work has been supported in part by FIIRESIN, Fideicomiso-UNAM (to RD-C) and DGAPA-UNAM1N203393 (to RJS-P).

===1993 [https://jamanetwork.com/journals/jamapsychiatry/article-abstract/496026 Nicotine Dependence and Major Depression]===
*There is, then, no evidence in these data that the occurrence of MDD in persons with a prior history of nicotine dependence might have been caused directly by recent persistent smoking.
*[https://sci-hub.st/10.1001/archpsyc.1993.01820130033006 PDF Version]
*Citation: Breslau N, Kilbey MM, Andreski P. Nicotine Dependence and Major Depression: New Evidence From a Prospective Investigation. Arch Gen Psychiatry. 1993;50(1):31–35. doi:10.1001/archpsyc.1993.01820130033006

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement (mood normalization) (other issues and diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

=='''Mental Health - Mental Illness'''==

===2022 [https://academic.oup.com/ntr/article-abstract/24/9/1405/6562456 E-Cigarette Provision to Promote Switching in Cigarette Smokers With Serious Mental Illness—A Randomized Trial]===
*This was the first prospective study to compare e-cigarette provision with assessments only to evaluate the appeal and impact of e-cigarettes on smoking behavior, carbon monoxide exposure, and nicotine dependence among smokers with Severe Mental Illness (SMI) who had tried but were unable to quit and were not currently interested in cessation treatment. The finding that e-cigarette provision led to significant reductions in smoking and carbon monoxide without increasing nicotine dependence has implications for reducing harm not only among the millions of smokers with SMI who struggle to quit, but also for other vulnerable smokers who cannot achieve cessation.
 

=='''Mental Health - OCD (Obsessive Compulsive Disorder)'''==
===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/ Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review]===
*Nicotine may ameliorate OC symptoms in severe, treatment-refractory [[Special:MyLanguage/Abbreviations|'''OCD''']] patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/pdf/12991_2020_Article_309.pdf PDF Version]
*Citation: Piacentino D, Maraone A, Roselli V, Berardelli I, Biondi M, Kotzalidis GD, Pasquini M. Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review. Ann Gen Psychiatry. 2020 Sep 30;19:57. doi: 10.1186/s12991-020-00309-z. PMID: 33014119; PMCID: PMC7528475.
 

=='''Mental Health - PTSD (Post Traumatic Stress Disorder)'''==
===2012 [https://www.hindawi.com/journals/aps/2012/265724/ Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study]===
*Smokers with PTSD report greater NA (Negative Affects) immediately prior to smoking and greater decreases in NA following smoking, and these findings are consistent with the observed patterns of brain activation in the current study. Thus, our findings provide a neurobiological basis that helps explain why individuals with PTSD are at greater risk of smoking and also experience greater difficulty quitting. The present study is not without its limitations. Our sample size was small and was predominately represented by female smokers.
*[https://downloads.hindawi.com/journals/aps/2012/265724.pdf PDF Version]
*Citation: Froeliger, B., Crowell Beckham, J., Feldman Dennis, M., Victoria Kozink, R., & Joseph McClernon, F. (2012). Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study. Advances in Pharmacological Sciences, 2012, 1–6. doi:10.1155/2012/265724
*Acknowledgement: Department of Veterans Affairs or the National Institutes of Health.
 

=='''Mental Health - Schizophrenia'''==
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fpsyt.2022.804055/full Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence]===
*Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
*[https://twitter.com/hbwardMD/status/1487037135299518474 Twitter thread about this study]
**Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055
***Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0149763420305042?via%3Dihub The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review]===
*Cognitive and early sensory alterations are core features of [https://en.wikipedia.org/wiki/Schizophrenia '''schizophrenia''']. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.
*[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 PDF Version]
**Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.

=== 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===
*Animal Study
*“Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
*Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
**Citation: Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)

===2017: [https://pubmed.ncbi.nlm.nih.gov/28441884/ Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging]===
*This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.
**Citation: Smucny J, Tregellas JR. Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging. J Psychopharmacol. 2017 Jul;31(7):801-811. doi: 10.1177/0269881117705071. Epub 2017 Apr 26. PMID: 28441884; PMCID: PMC5963521.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Citation: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===
*The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.
*[https://sci-hub.st/10.1016/j.mehy.2009.02.017 PDF Version]
**Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

===2007: [https://pmc.ncbi.nlm.nih.gov/articles/PMC2702723/ Nicotinic Interactions with Antipsychotic Drugs, Models of Schizophrenia and Impacts on Cognitive Function]===
*Human and Animal study
*Nicotinic receptor systems in the brain are important for a variety of aspects of cognitive function impaired in schizophrenia and aggravated by antipsychotic drugs. Nicotine and selective nicotinic α7 and α4β2 agonists can significantly improve learning, memory and attention. Nicotine and nicotine agonists can reduce some of the cognitive impairments caused by some antipsychotic drugs as well as reduce cognitive impairments seen in the NMDA glutamate blockade animal model of schizophrenia.
**Citation: Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007 Oct 15;74(8):1182-91. doi: 10.1016/j.bcp.2007.07.019. Epub 2007 Jul 20. PMID: 17714691; PMCID: PMC2702723.
***Acknowledgement: Research presented was supported by a grant from the National Institute of Mental Health grant MH64494.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
**Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.
 

='''Movement Disorders (not diagnosis specific)'''=
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/ Role for the nicotinic cholinergic system in movement disorders; therapeutic implications]===
*Animal Study
*Several [[Special:MyLanguage/Abbreviations|'''nAChR''']] subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/pdf/nihms600497.pdf PDF Version]
*Citation: Quik M, Zhang D, Perez XA, Bordia T. Role for the nicotinic cholinergic system in movement disorders; therapeutic implications. Pharmacol Ther. 2014 Oct;144(1):50-9. doi: 10.1016/j.pharmthera.2014.05.004. Epub 2014 May 14. PMID: 24836728; PMCID: PMC4149916.
*Acknowledgements: This work was supported by grants NS59910 and NS 65851 from the National Institutes of Health.
 

='''Multiple Sclerosis - Humans / Experimental Autoimmune Encephalomyelitis (EAE) - Animals'''=

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2015 [https://pubmed.ncbi.nlm.nih.gov/25813705/ Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis]===
*Amimal study
*We found that reduction of ependymal cell proliferation correlated with inflammation in the same area, which was relieved by the administration of nicotine. Further, increased numbers of oligodendrocytes (OLs) were observed after nicotine treatment. These findings give a new insight into the mechanism of how nicotine functions to attenuate EAE.
*[https://sci-hub.st/10.1016/j.neuroscience.2015.03.031 PDF Full Study]
**Citation: Gao Z, Nissen JC, Legakis L, Tsirka SE. Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis. Neuroscience. 2015 Jun 25;297:11-21. doi: 10.1016/j.neuroscience.2015.03.031. Epub 2015 Mar 23. PMID: 25813705; PMCID: PMC4428965.
***Acknowledgement: The work was supported by NMSS PP1815, NIH R01NS42168, NIH IRACDA K12GM102778.

===2015 [https://pubmed.ncbi.nlm.nih.gov/26209886/ Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients]===
*The data obtained highlight the role of α7 receptor subtype in the modulation of anti-inflammatory cytokines also in MS. Moreover the ability of nicotine to up-regulate the expression of α7 receptor subtype in RR-MS patients, indicates that nicotinic receptor stimulation may contribute to down-modulate the inflammation occurred in MS by a positive feedback control of its expression.
*[https://sci-hub.st/10.1016/j.intimp.2015.06.034 PDF Full paper]
**Citation: Reale M, Di Bari M, Di Nicola M, D'Angelo C, De Angelis F, Velluto L, Tata AM. Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients. Int Immunopharmacol. 2015 Nov;29(1):152-7. doi: 10.1016/j.intimp.2015.06.034. Epub 2015 Jul 23. PMID: 26209886.
***Acknowledgement: This work was supported by FISM – Fondazione Italiana Sclerosi Multipla – Cod. 2013/R/25. MDB was supported by fellowship on FISM project 2013/R/25.

===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/ The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components]===
*Animal Study
*Our results show that nicotine reduces the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an [[Special:MyLanguage/Abbreviations|'''EAE/MS''']] therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/pdf/pone.0107979.pdf PDF Version]
**Citation: Gao Z, Nissen JC, Ji K, Tsirka SE. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One. 2014 Sep 24;9(9):e107979. doi: 10.1371/journal.pone.0107979. PMID: 25250777; PMCID: PMC4176721.
***Acknowledgements: This work was supported by National Multiple Sclerosis Society awards CA1044A1 and PP181, National Aeronautics and Space Administration NNA14AB04A and National Institutes of Health R01NS42168 (ST), and National Institutes of Health K12GM102778 to JN.

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.
 

='''Narcolepsy'''=

===2021: [https://www.authorea.com/doi/full/10.22541/au.162126605.51833119 The therapeutic use of medical nicotine in narcolepsy]===
*PDF: [https://www.researchgate.net/profile/Carolina-Diamandis/publication/351648895_The_therapeutic_use_of_medical_nicotine_in_narcolepsy/links/60aa9cb945851522bc10a4c1/The-therapeutic-use-of-medical-nicotine-in-narcolepsy.pdf The therapeutic use of nicotine in narcolepsy]

===2012: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3311418/ Narcolepsy with Cataplexy Masked by the Use of Nicotine]===
*

===2010: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2823281/ A Novel Approach to Treating Morning Sleep Inertia in Narcolepsy]===
*

='''Nicotine Used With Other Substances'''=

===2021 [https://pubmed.ncbi.nlm.nih.gov/34119664/ Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats]===
*Animal Study
*The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA. (Note: AKA ecstasy)
*Citation: Kowsari G, Mehrabi S, Soleimani Asl S, Pourhamzeh M, Mousavizadeh K, Mehdizadeh M. Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats. J Chem Neuroanat. 2021 Jun 10;116:101986. doi: 10.1016/j.jchemneu.2021.101986. Epub ahead of print. PMID: 34119664.

='''Oral / Jaw'''=
===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
*Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).
*Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, [https://en.wikipedia.org/wiki/Edema oedema], and [https://en.wikipedia.org/wiki/Trismus trismus] in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
*Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
*Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444372/ Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program]===
*The results of this study confirm that chewing the tested nicotine replacement gum as recommended in a ‘real world’ active smoking cessation program produces a statistically significant change in the parameter of whitening as measured by change from baseline versus the negative control (Microtab) following 6 weeks in a smoking cessation programme. The Vita® Shade Guide (the secondary outcome measure) supported the trend of stain improvement. These results support the efficacy of the tested nicotine replacement gum in stain reduction, in arresting the progression of tooth stain and in shade lightening.
*Acknowledgement: The study was fully funded by McNeil AB who is the manufacturer of the test and control products. It was designed by McNeil AB in consultation with HW and DOM. The study was run, participants recruited, smoking cessation intervention administered and data collected by the team of research staff at the Oral Health Services Research Centre at University College Cork under the leadership of HW with consultant input from DOM. RK carried out the clinical examinations but was blinded to intervention allocation. The data were analysed by McNeil AB with input from HW and DOM. The study was externally monitored by MDS Pharma Services, UK and conducted to ICH GCP standards. The data were interpreted by HW, DOM and RK. The manuscript was drafted by HW with editorial comment from the other authors. HW decided to submit the manuscript for publication.
*Citation: Whelton H, Kingston R, O'Mullane D, Nilsson F. Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program. BMC Oral Health. 2012 Jun 13;12:13. doi: 10.1186/1472-6831-12-13. PMID: 22695211; PMCID: PMC3444372.
 

='''Pain / Analgesic'''=
===2024: [https://pubmed.ncbi.nlm.nih.gov/39719676/ Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial]===
*Postoperative pain scores at rest and on movement were lower in the nicotine group than in the placebo group at 6 hours, 12 hours, and 24 hours after surgery (P<0.05). Postoperative morphine consumption was lower in the nicotine group than in the placebo group (9.92 ± 4.0 vs. 15.9 ± 5.0 mg, respectively; P=0.0002).
**Citation: Maheshwari A, Gupta M, Garg B, Singh AK, Khanna P. Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial. J Neurosurg Anesthesiol. 2024 Dec 25. doi: 10.1097/ANA.0000000000001022. Epub ahead of print. PMID: 39719676.
***Acknowledgement: Paywalled, can not access

===2023: [https://pubmed.ncbi.nlm.nih.gov/37132069/ Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study]===
*Perioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.
**Citation: Zhu C, Bi Y, Wei K, Tao K, Hu L, Lu Z. Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study. Addiction. 2023 Aug;118(8):1579-1585. doi: 10.1111/add.16224. Epub 2023 May 19. PMID: 37132069.
***Acknowledgement: Shanghai Municipal Science and Technology Commission. Grant Number: 17411960400

===2023: [https://www.mdpi.com/1424-8247/16/12/1665 The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis]===
*Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
**Citation: Luo Y, Yang Y, Schneider C, Balle T. The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis. Pharmaceuticals. 2023; 16(12):1665. https://doi.org/10.3390/ph16121665
***Acknowledgement: This work was funded by the Australian Research Council LP160100560.

===2023 [https://www.sciencedirect.com/science/article/abs/pii/S0014299923000298?via%3Dihub Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron]===
*Animal Study
*Nicotine-induced antinociception was inhibited by intrathecal pre-treatment with yohimbine, an α2 adrenergic receptor antagonist. These results indicated that nicotine may suppress BCAO-induced mechanical hypersensitivity through the activation of the descending pain control system via orexin neurons.
**Citation: Nakamoto, K., Matsuura, W., & Tokuyama, S. (2023). Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron. European journal of pharmacology, 175518. Advance online publication. https://doi.org/10.1016/j.ejphar.2023.175518
***Acknowledgement: This work was supported by the Smoking Research Foundation (FP01807092).

===2023: [https://pubmed.ncbi.nlm.nih.gov/36947193/ Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials]===
*Perioperative use of NP significantly improved postoperative pain, even when opioids were administered or prescribed. Nevertheless, the clinical relevance should be interpreted with caution, owing to the effect sizes of the summary measures and methodological issues. The analgesic potential of NP as an adjuvant therapy to regulate pain and acute inflammation may offer certain clinical advantages, thus warranting further investigation.
**Citation: da Silva Barbirato D, de Melo Vasconcelos AF, Dantas de Moraes SL, Pellizzer EP, do Egito Vasconcelos BC. Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials. Eur J Clin Pharmacol. 2023 May;79(5):589-607. doi: 10.1007/s00228-023-03475-7. Epub 2023 Mar 22. PMID: 36947193.
***Acknowledgement: Paywalled, can't access

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, oedema, and trismus in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
**Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
***Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/ Acute Analgesic Effects of Nicotine and Tobacco in Humans: A Meta-Analysis]===
*Pain and tobacco smoking are both highly prevalent and comorbid conditions, current smoking has been associated with more severe chronic pain and physical impairment, and acute nicotine-induced analgesia could make smoking more rewarding and harder to give up.
*Moderation analyses further revealed that acute analgesic effects may be achieved regardless of nicotine delivery method, current smoking status, pain induction modality, study design, or control condition, and that such effects may be more robust among men than women.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/pdf/nihms-774195.pdf PDF Version]
**Citation: Ditre JW, Heckman BW, Zale EL, Kosiba JD, Maisto SA. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain. 2016;157(7):1373-1381. doi:10.1097/j.pain.0000000000000572 (viewed Oct 5, 2021)
***Acknowledgement: This research was supported by NIH Grant Nos. R21DA034285 and R21DA038204 awarded to Joseph W. Ditre, NIH Grant Nos. F31DA033058 and T32DA007288 awarded to Bryan W. Heckman, NIH Grant No. F31DA039628 awarded to Emily L. Zale, and NIH Grant No. 2K05 AA16928 awarded to Stephen A. Maisto.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

===2011 [https://journals.lww.com/ejanaesthesiology/Fulltext/2011/08000/Randomised_trial_of_intranasal_nicotine_and.7.aspx Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women]===
*Intraoperative use of intranasal nicotine has a sustained opioid-sparing effect in non-smoking women undergoing gynaecological procedures and is associated with a higher frequency of nausea.
*[https://sci-hub.st/10.1097/EJA.0b013e328344d998 PDF Version]
*Citation: Jankowski, Christopher J.; Weingarten, Toby N.; Martin, David P.; Whalen, Francis X.; Gebhart, John B.; Liedl, Lavonne M.; Danielson, David R.; Nadeau, Ashley M.; Schroeder, Darrell R.; Warner, David O.; Sprung, Juraj Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women, European Journal of Anaesthesiology (EJA): August 2011 - Volume 28 - Issue 8 - p 585-591 doi: 10.1097/EJA.0b013e328344d998
*Acknowledgements: The present work was supported solely by the Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

===2008 [https://journals.lww.com/anesthesia-analgesia/Fulltext/2008/09000/Transdermal_Nicotine_for_Analgesia_After_Radical.48.aspx Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy]===
*The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in postoperative opioid consumption in nonsmoking men undergoing [[Special:MyLanguage/Abbreviations|'''RRP''']] in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
*[https://sci-hub.se/10.1213/ane.0b013e31816f2616# PDF Version]
*Citation: Habib, Ashraf S., MBBCh, MSc, FRCA*; White, William D., MPH*; El Gasim, Magdi A., MD*; Saleh, Gamal, MD*; Polascik, Thomas J., MD†; Moul, Judd W., MD†; Gan, Tong J., MB, FRCA* Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy, Anesthesia & Analgesia: September 2008 - Volume 107 - Issue 3 - p 999-1004 doi: 10.1213/ane.0b013e31816f2616

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12131122/ Isoflurane hyperalgesia is modulated by nicotinic inhibition]===
*Animal study
*Female mice had significant [https://en.wikipedia.org/wiki/Hyperalgesia hyperalgesia] from [https://en.wikipedia.org/wiki/Isoflurane isoflurane]. Nicotine administration prevented isoflurane-induced hyperalgesia without altering the antinociception produced by higher isoflurane concentrations.
**Citation: Flood P, Sonner JM, Gong D, Coates KM. Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology. 2002 Jul;97(1):192-8. doi: 10.1097/00000542-200207000-00027. PMID: 12131122.
***Acknowledgement: 1P01GM47818/GM/NIGMS NIH HHS/United States, K08GM00695/GM/NIGMS NIH HHS/United States
 

='''Parkinson Disease'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/40465192/ Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease]===
*"In conclusion, these findings suggest potential therapeutic mechanisms of the identified constituents in PD and may provide a basis for future preclinical and clinical studies to further explore their neuroprotective effects."
**Citation: Tusar MTT, Munna MMR, Ahmed MH, Rahman MM, Fatema K, Islam KM, Ali MS. Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease. Cell Biochem Biophys. 2025 Jun 4. doi: 10.1007/s12013-025-01791-6. Epub ahead of print. PMID: 40465192.
***The authors declare no competing interests. (No funding information provided on the version viewed at the link above.)

===2024 [https://www.sciencedirect.com/science/article/abs/pii/S0967586824003849 The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial]===
*The results of our study indicated that nicotine consumption in an isocaloric diet, while preventing a decrease in anthropometric indices, leads to improvements in motor indices and a reduction in alpha-synuclein levels. Additional and larger controlled trials are required to validate these findings.
**Citation: Lorvand Amiri H, Hassan Javanbakht M, Mohammad Baghbanian S, Parsaeian M. The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial. J Clin Neurosci. 2024 Sep 30;129:110845. doi: 10.1016/j.jocn.2024.110845. Epub ahead of print. PMID: 39353253.
***Acknowledgement: This work was supported by the Tehran University of Medical Sciences. (Project No. 53161).

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38430248/ Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease] ===
*Animal study (worms with humanised neurons)
*This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction.
*At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS.
*We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.
*''Note: highly technical brain biochemistry, appears to be important however (ed.)'' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586504/ Paper on the UPS and it's purpose] for info.
**Citation: Ullah I, Uddin S, Zhao L, Wang X, Li H. Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease. Exp Brain Res. 2024 Apr;242(4):971-986. doi: 10.1007/s00221-023-06765-9. Epub 2024 Mar 2. PMID: 38430248.
***Acknowledgement: This study was supported by the Special International Cooperation Project of the Ministry of Science and Technology (2012DFA30480); National Natural Science Foundation of China (No. 81403145); Natural Science Foundation of Gansu Province (No. 20JR10RA602); Fundamental Research Funds for the Central Universities of China (lzujbky—2017-206, lzujbky-2018-136); Science and Technology Cooperation Program of Gansu Academy of Sciences (grant number 2019HZ-02); Program of Lanzhou Science and Technology Foundation (Grant number 2010-1-154). Major science and technology project of Gansu province (23ZDFA013), Natural Science Foundation of Gansu province (20JR10RA602).

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnagi.2023.1223310/full Changes in smoking, alcohol consumption, and the risk of Parkinson’s disease] ===
*A total of 3,931,741 patients were included.
*Compared to the sustained non-smokers, sustained light smokers, sustained moderate smokers, and sustained heavy smokers had a lower risk of PD.
*Compared to those who sustained non-drinking, sustained light drinkers, sustained moderate drinkers, and sustained heavy drinkers showed decreased risk of PD.
*Among non-drinkers, those who started drinking to a light level were at decreased risk of PD. Among non-smoking and non-drinking participants, those who initiated smoking only, drinking only, and both smoking and drinking showed decreased risk of PD.
*Smoking is associated with decreased risk of PD with a dose–response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.
**Citation: Jung SY, Chun S, Cho EB, Han K, Yoo J, Yeo Y, Yoo JE, Jeong SM, Min JH, Shin DW. Changes in smoking, alcohol consumption, and the risk of Parkinson's disease. Front Aging Neurosci. 2023 Sep 13;15:1223310. doi: 10.3389/fnagi.2023.1223310. PMID: 37771519; PMCID: PMC10525683.
***Acknowledgement: J-HM received a grant from the National Research Foundation of Korea and SMC Research and Development Grant. J-HM has lectured, consulted, and received Honoria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Sanofi Genzyme, Teva-Handok, UCB, Samsung Bioepis, Mitsubishi Tanabe Pharma, and Roche.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36817162/ Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.] ===
*Animal Study
*Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo.
*In summary, Nic pretreatment ameliorates MPTP-induced dyskinesia and anxiety-like behavior in mice with PD. Nic was found to alleviate neuroapoptosis by improving nigrostriatal dopaminergic damage, reducing the accumulation of pathological p-α-syn, and inhibiting microglia activation and pro-inflammatory factor expression in the substantia nigra and striatal regions of mice brain under MPTP stimulation. These neuroprotective effects of Nic may be achieved by modulating the JNK and ERK signaling pathways in the nigrostriatal system, which was further confirmed by the pretreatment of 5-MOP to decline the brain metabolic activity of Nic.
**Citation: Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. PMID: 36817162; PMCID: PMC9932206.
***Acknowledgement: This study received funding from the National Science Foundation of China (Grant No. 32072344, 82101506, 32272455), the Scientific and Technological Project of Henan Province of China (Grant No. 182102310157) and the Scientific and Technological Project of China Tobacco Jiangsu Industrial Co., Ltd. (No. H202002). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Authors JX, RJ, and ZG were employed by China Tobacco Jiangsu Industrial Co., Ltd.

===2023: [https://jamanetwork.com/journals/jamaneurology/article-abstract/2805037 Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune]===
*“Parkinson disease risk was substantially lower among Black veterans and EVER-SMOKERS (OR 0.49, 95% CI: 0.40-0.61).
**Citation: Goldman SM, Weaver FM, Stroupe KT, Cao L, Gonzalez B, Colletta K, Brown EG, Tanner CM. Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune. JAMA Neurol. 2023 Jul 1;80(7):673-681. doi: 10.1001/jamaneurol.2023.1168. PMID: 37184848; PMCID: PMC10186205.
***Acknowledgement: This research was supported by clinical science research and development merit award I01 CX002040-01 from the US Department of Veterans Affairs. Support for Veterans Administration (VA)/Centers for Medicare & Medicaid Services data was from the US Department of Veterans Affairs, VA Health Services Research and Development Service, and project numbers SDR 02-237 and 98-004 from the VA Information Resource Center. Dr Weaver reported receiving grants from the Edward Hines, Jr VA Hospital during the conduct of the study and outside the submitted work. Dr Brown reported receiving grants from the Michael J. Fox Foundation and the National Institute on Aging and personal fees from Gateway Consulting, LLC, outside the submitted work. Dr Tanner reported receiving personal fees from Lundbeck Pharma, CNS Ratings, Adamas, Cadent, and Evidera; serving on advisory boards for Kyowa Kirin, Acorda, Australia Parkinson’s Mission; serving on a clinical trial steering committee for Jazz Pharmaceuticals/Cavion; and receiving grants from the National Institutes of Health, Biogen Idec, Parkinson Foundation, Michael J. Fox Foundation, Department of Defense Parkinson’s Research Program, Roche, Genentech, BioElectron, and Gateway Institute for Brain Research, LLC, outside the submitted work. No other disclosures were reported.

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602090/ Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-induced Toxicities in Cell Culture]===
*Preprint, not peer-reviewed.
*In summary, our results not only support neuroprotective effects of nicotine and butyrate in countering Fe and Mn toxicities but indicate a synergistic protection by combination of the two. Moreover, distinct mechanisms of action for each metal, i.e., nicotinic receptor for nicotine and FA3R for butyrate are indicated. Further exploitation of mechanisms of action of butyrate and nicotine may provide novel targets for metal toxicities and/or amelioration of neurodegenerative diseases.
**Citation: Tizabi Y, Getachew B, Aschner M. Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases. Res Sq [Preprint]. 2023 Oct 5:rs.3.rs-3389904. doi: 10.21203/rs.3.rs-3389904/v1. Update in: Neurotox Res. 2023 Dec 14;42(1):3. doi: 10.1007/s12640-023-00682-z. PMID: 37886507; PMCID: PMC10602090.
***Acknowledgement: Supported in part by: NIH/NIAAA R03 AA022479 and NIH/NIGMS (2 SO6 GM08016‐39) (YT), and NIEHS R01ES10563 and R01ES07331 (MA).

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36857384/ Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment.] ===
*Insect study
*We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.
**Citation: Carvajal-Oliveros A, Dominguez-Baleón C, Sánchez-Díaz I, Zambrano-Tipan D, Hernández-Vargas R, Campusano JM, Narváez-Padilla V, Reynaud E. Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment. PLoS One. 2023 Mar 1;18(3):e0282348. doi: 10.1371/journal.pone.0282348. PMID: 36857384; PMCID: PMC9977059.
***Acknowledgement: This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 255478 and by Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (DGAPA-PAPIIT) grant number IN206517) ER was the recipient of the grants. AC received fellowships (446128) from CONACYT, PAEP-UNAM and Alianza del Pacífico- AGCID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

===2021 [https://www.nature.com/articles/s41598-021-88910-4 Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels]===
*Insect study
*In conclusion our data show that the PD model by expression of Sph-1 in dopaminergic neurons provides a good opportunity to study the early prodromal stages of PD, while also the late onset symptoms such as neurodegeneration and motor impairment in aged animals. On the other hand, working on this animal model has allowed us to advance on the therapeutic effects of nicotine treatment over several PD-linked features. The protective effect of nicotine appears to be specific for the genotype predisposed to develop a parkinsonian phenotype and provide a hint on the idea that nicotine treatment even in later stages of the disease could be beneficial to patients. Our findings provide new ideas that contribute to a better understanding on the mechanisms underlying the positive effects of nicotine in PD.
**Citation: Carvajal-Oliveros, A., Domínguez-Baleón, C., Zárate, R.V. et al. Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Sci Rep 11, 9579 (2021). https://doi.org/10.1038/s41598-021-88910-4
***Acknowledgement: This work was supported by the CONACyT (Grant Number 255478) and by DGAPA-PAPIIT (Grant Number IN206517).

=== 2020: [https://n.neurology.org/content/94/20/e2132 Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors] ===
*In contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.
**Citation: Mappin-Kasirer B, Pan H, Lewington S, Kizza J, Gray R, Clarke R, Peto R. Tobacco smoking and the risk of Parkinson disease: A 65-year follow-up of 30,000 male British doctors. Neurology. 2020 May 19;94(20):e2132-e2138. doi: 10.1212/WNL.0000000000009437. Epub 2020 May 5. PMID: 32371450; PMCID: PMC7526668.

===2020 [https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqaa186/5876214?redirectedFrom=fulltext Dietary nicotine intake and risk of Parkinson disease: a prospective study]===
*At 26 year follow-up, women with greater dietary nicotine intake had a lower risk of [[Special:MyLanguage/Abbreviations|'''Parkinson Disease (PD)''']] than those with lower intake. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea.
*[https://sci-hub.st/10.1093/ajcn/nqaa186 PDF Version]
**Citation: Chaoran Ma, Samantha Molsberry, Yanping Li, Michael Schwarzschild, Alberto Ascherio, Xiang Gao, Dietary nicotine intake and risk of Parkinson disease: a prospective study, The American Journal of Clinical Nutrition, Volume 112, Issue 4, October 2020, Pages 1080–1087, doi: 10.1093/ajcn/nqaa186
***Acknowledgements: Supported by National Institute of Neurological Disorders and Stroke at the NIH grant 1R03NS093245-01A1 (to XG). The Nurses’ Health Study is supported by the NIH through grant UM1 CA186107. The Health Professionals Follow-up Study cohort is supported by the NIH through grant U01 CA167552.

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2018 [https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0625-y Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6]===
*Animal study
*The reduced prevalence of Parkinson’s disease in tobacco users is a fascinating phenomenon that is not understood. This study suggests a mechanistic explanation for how tobacco users are protected from Parkinson’s and how the tobacco component nicotine confers neuroprotection; more specifically, nicotine suppresses SIRT6 which confers resistance to neuron and cell death. Few effective treatments exist that prevent neuron death for those suffering from Parkinson’s and other neurodegenerative disorders. The identification of SIRT6 as potentially pathogenic and as a therapeutic target for suppression opens a novel line of research for the treatment of neurodegeneration.
**Citation: Nicholatos, J.W., Francisco, A.B., Bender, C.A. et al. Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6. acta neuropathol commun 6, 120 (2018). https://doi.org/10.1186/s40478-018-0625-y
***Acknowledgement: S.L. and J.W.N. were in part supported by a grant from American Federation for Aging Research (AFAR, grant # 2015–030). S.L. received seed grant funding from the Cornell University Center for Vertebrate Genomics. J.W.N. was supported by a Glenn/AFAR Scholarship for Research in the Biology of Aging.

===2017 [https://academic.oup.com/ije/article/46/3/872/2656164 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Non-smoking men who used snus had a 60% lower risk of Parkinson’s disease compared with never snus users.
**Citation: Yang F, Pedersen NL, Ye W, Liu Z, Norberg M, Forsgren L, Trolle Lagerros Y, Bellocco R, Alfredsson L, Knutsson A, Jansson JH, Wennberg P, Galanti MR, Lager ACJ, Araghi M, Lundberg M, Magnusson C, Wirdefeldt K. Moist smokeless tobacco (Snus) use and risk of Parkinson's disease. Int J Epidemiol. 2017 Jun 1;46(3):872-880. doi: 10.1093/ije/dyw294. PMID: 27940486.
***Acknowledgement: This work was supported by the Swedish Research Council (grant number 521-2013-2488 to N.L.P.) and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (Y.T.L.).

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Author/Acknowledgements: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/ Nicotinic receptors as CNS targets for Parkinson’s disease]===
*Human and animal references
*Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/pdf/nihms32016.pdf PDF Version]
**Citation: Quik M, Bordia T, O'Leary K. Nicotinic receptors as CNS targets for Parkinson's disease. Biochem Pharmacol. 2007 Oct 15;74(8):1224-34. doi: 10.1016/j.bcp.2007.06.015. Epub 2007 Jun 17. PMID: 17631864; PMCID: PMC2046219.
***Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Parkinson's Disease''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against '''Parkinson's Disease''' (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Pemphigus Vulgaris'''=

===2001: [https://pubmed.ncbi.nlm.nih.gov/11737449/ Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire]===
*The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked.
*The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system.
**Citation: Brenner S, Tur E, Shapiro J, Ruocco V, D'Avino M, Ruocco E, Tsankov N, Vassileva S, Drenovska K, Brezoev P, Barnadas MA, Gonzalez MJ, Anhalt G, Nousari H, Ramos-e-Silva M, Pinto KT, Miranda MF. Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire. Int J Dermatol. 2001 Sep;40(9):562-9. doi: 10.1046/j.1365-4362.2001.01266.x. Erratum in: Int J Dermatol. 2003 Sep;42(9):760. Silva MR [corrected to Ramos-e-Silva M]. PMID: 11737449.

===2000: [https://jamanetwork.com/journals/jamadermatology/fullarticle/189739 A Case of Pemphigus Vulgaris Improved by Cigarette Smoking]===
*The patient reported an inverse relationship between smoking and pemphigus flares. He observed a worsening of the pemphigus when he stopped smoking. Nicotine patches were prescribed, but he began smoking cigarettes again instead. On average, he smokes 15 cigarettes per day. One week after he began smoking again, his pemphigus rapidly started to clear.
**Citation: Mehta JN, Martin AG. A case of pemphigus vulgaris improved by cigarette smoking. Arch Dermatol. 2000 Jan;136(1):15-7. doi: 10.1001/archderm.136.1.15. PMID: 10632179.
 

='''Pregnancy'''=
==Preeclampsia==

===2024: [https://www.sciencedirect.com/science/article/abs/pii/S0303720724003022 Nicotine increases hepatocyte transthyretin turnover: a possible mechanism for the protective effect of smoking on preeclampsia?]===
*Nicotine exposure increases hepatocyte synthesis, secretion and uptake of transthyretin as well as cell uptake of soluble endoglin. Nicotine may protect against preeclampsia by increasing serum TTR which can bind soluble endoglin and remove it from the circulation. Further research is required to better understand the role of transthyretin and nicotine in mitigating preeclampsia.
**Citation: Young M, McLeod DSA, Richard K. Nicotine increases hepatocyte transthyretin turnover: A possible mechanism for the protective effect of smoking on preeclampsia? Mol Cell Endocrinol. 2025 Feb 1;597:112446. doi: 10.1016/j.mce.2024.112446. Epub 2024 Dec 24. PMID: 39725350.
***Acknowledgement: This study was funded by the Science Education and Research Committee, Pathology Queensland.
 

='''Psoriasis'''=

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.
 

='''Pyoderma Gangrenosum'''=

===2004 [https://pubmed.ncbi.nlm.nih.gov/15204166/ Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream]===
*Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.
*[https://scihubtw.tw/10.1080/09546630310019364 PDF Version]
**Citations:Patel GK, Rhodes JR, Evans B, Holt PJ. Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream. J Dermatolog Treat. 2004 Apr;15(2):122-5. doi: 10.1080/09546630310019364. PMID: 15204166.

===1998 [https://jamanetwork.com/journals/jamadermatology/fullarticle/189304?fbclid=IwAR33gpEktRMf2Q0v5Btl9C5E8gmXw-ZP8_gDFt6sebxUBpXE_WfVt-o-mSw Nicotine for Pyoderma Gangrenosum]===
*Herein we describe a patient with pyoderma gangrenosum who responded twice to topical nicotine within 4 weeks and 3 months, respectively, without any adverse effects.
*[https://scholar.google.com/scholar_url?url=https://jamanetwork.com/journals/jamadermatology/articlepdf/189304/dce8005.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=Z2aqX4SnOc2rywTPj5aYDw&scisig=AAGBfm1pz6ffl3a23G__I3APgBLpY6Cofw PDF Version]
**Citation: Wolf R, Ruocco V. Nicotine for Pyoderma Gangrenosum. Arch Dermatol. 1998;134(9):1071–1072. doi:10.1001/archderm.134.9.1071

===1995 [https://pubmed.ncbi.nlm.nih.gov/8537562/ Successful treatment of pyoderma gangrenosum with nicotine chewing gum]===
*We used nicotine chewing gum for the treatment of pyoderma gangrenosum with remarkable results. We strongly suggest that nicotine chewing gum may not only be beneficial in treating pyoderma gangrenosum but may also be useful in treating other skin disorders with prominent neutrophilic infiltrations such as Behcet's disease, Sweet disease, allergic vasculitis, and recurrent oral aphthae, the last of which is known to respond to smoking.
*[https://sci-hub.st/10.1111/j.1346-8138.1995.tb03904.x PDF Version]
**Citation: Kanekura T, Kanzaki T. Successful treatment of pyoderma gangrenosum with nicotine chewing gum. J Dermatol. 1995 Sep;22(9):704-5. doi: 10.1111/j.1346-8138.1995.tb03904.x. PMID: 8537562.
 

='''Rett syndrome'''=

===2016: [https://www.nature.com/articles/cr201648 Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus]===
*Animal Study
*In addition, application of PNU282987 or nicotine rescued impaired social interaction and anxiolytic behaviors in Chat-Mecp2−/y mice.
*Nicotine appears to be the primary agent in cigarettes that can target all nAChRs, including α7 nAChRs. Application of nicotine also rescued the behavioral phenotypes of Chat-Mecp2−/y mice. Long-term delivery of nicotine in the hippocampus also improved social memory in WT mice...Of particular importance, intracerebral infusion of PNU282987 or nicotine rescued the behavioral defects in Chat-Mecp2−/y mice. These findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.
**Citation: Zhang Y, Cao SX, Sun P, He HY, Yang CH, Chen XJ, Shen CJ, Wang XD, Chen Z, Berg DK, Duan S, Li XM. Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus. Cell Res. 2016 Jun;26(6):728-42. doi: 10.1038/cr.2016.48. Epub 2016 Apr 22. PMID: 27103432; PMCID: PMC4897179.
***Acknowledgement: This work was supported by the National Natural Science Foundation of China for Distinguished Young Scientists (81225007), Key Project of the National Natural Science Foundation of China (31430034), Major Research Plan of the National Natural Science Foundation of China (91432306), Funds for Creative Research Groups of China (81221003), Program for Changjiang Scholars and Innovative Research Team in University, and Fundamental Research Funds for the Central Universities. This work was also sponsored by the Zhejiang Province Program for Cultivation of High-level Health Talents.
 

='''Sarcoidosis'''=

===2021 [https://journal.chestnet.org/article/S0012-3692(21)01282-4/fulltext Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis]===
===2021 [https://journal.chestnet.org/article/S0012-3692(21)00962-4/fulltext A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis]===
*Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC.
**Citation: A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis, Crouser, Elliott D. et al. CHEST, Volume 160, Issue 4, 1340 - 1349

===2013 [https://journal.chestnet.org/article/S0012-3692(13)60095-1/fulltext Nicotine Treatment Improves Toll-Like Receptor 2 and Toll-Like Receptor 9 Responsiveness in Active Pulmonary Sarcoidosis]===
*The immune phenotype of patients with symptomatic [[wikipedia:Sarcoidosis|'''sarcoidosis''']] treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
*[https://www.researchgate.net/profile/Mark_Julian/publication/230645268_Nicotine_Treatment_Improves_TLR2_and_TLR9_Responsiveness_in_Active_Pulmonary_Sarcoidosis/links/556ca4af08aeab77722318be/Nicotine-Treatment-Improves-TLR2-and-TLR9-Responsiveness-in-Active-Pulmonary-Sarcoidosis.pdf PDF Version]
**Citation: Mark W. Julian, MS; Guohong Shao, MD; Larry S. Schlesinger, MD; Qin Huang, MD; David G. Cosmar, BA; Nitin Y. Bhatt, MD; Daniel A. Culver, MD, FCCP; Robert P. Baughman, MD, FCCP; Karen L. Wood, MD, FCCP; and Elliott D. Crouser, MD - ORIGINAL RESEARCH DIFFUSE LUNG DISEASE| VOLUME 143, ISSUE 2, P461-470, FEBRUARY 01, 2013, DOI 10.1378/chest.12-0383
***Acknowledgements: This work was supported by the American Thoracic Society and the Foundation for Sarcoidosis Research. © 2013 American College of Chest Physicians

===1988:[https://thorax.bmj.com/content/43/7/516.abstract Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.]===
*These finding support the possibility that smokers, particularly those with a prominent accumulation of alveolar macrophages in the lower respiratory tract, may be less likely to develop sarcoidosis.
**Citation: Valeyre D, Soler P, Clerici C, et alSmoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.Thorax 1988;43:516-524.
 

='''Seizures / Epilepsy'''=
*See also:
**Video: News 5: [https://www.youtube.com/watch?v=Ztvf45coKZk Nicotine Stops Seizures]

===2024 [https://www.neurology.org/doi/10.1212/WNL.0000000000209790/ Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch]===
*"Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep."
*"Our case highlights that there may be mechanisms by which nicotine assists with seizure cessation in specific populations of individuals with SHE."
**Citation: Nam S, Von Stein EL, Meador KJ, Levy RJ, Gallentine W, Li Y. Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch. Neurology. 2024 Oct 8;103(7):e209790. doi: 10.1212/WNL.0000000000209790. Epub 2024 Sep 9. PMID: 39250747; PMCID: PMC11385953.

===2021 [https://pubmed.ncbi.nlm.nih.gov/34763266/ Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients]===
*This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.
**Citation: Brodtkorb E, Myren-Svelstad S, Knudsen-Baas KM, Nakken KO, Spigset O. Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients. Epilepsy Res. 2021 Oct 25;178:106792. doi: 10.1016/j.eplepsyres.2021.106792. Epub ahead of print. PMID: 34763266.

===2021 [https://www.pedneur.com/article/S0887-8994(21)00147-8/fulltext Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy]===
*Nevertheless, the two siblings reported here add to the small number of pediatric case reports regarding the successful use of nicotine patches in ADSHE.
*Journal Pre-Proof [https://www.pedneur.com/action/showPdf?pii=S0887-8994%2821%2900147-8 PDF Version]
**Citation: Nguyen SM, Deering L, Nelson GT, McDaniel SS, Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy, Pediatric Neurology (2021), doi:10.1016/j.pediatrneurol.2021.07.006.

===2021 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable."
*"Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031.

===2020 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction."
*"Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031

===2020 [https://pubmed.ncbi.nlm.nih.gov/32097883/ Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy]===
*"Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions."
**Citation: Lossius K, de Saint Martin A, Myren-Svelstad S, Bjørnvold M, Minken G, Seegmuller C, Valenti Hirsch MP, Chelly J, Steinlein O, Picard F, Brodtkorb E. Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy Behav. 2020 Apr;105:106944. doi: 10.1016/j.yebeh.2020.106944. Epub 2020 Feb 22. PMID: 32097883.

===2018 [https://www.dovepress.com/sleep-related-hypermotor-epilepsy-prevalence-impact-and-management-str-peer-reviewed-fulltext-article-NSS Sleep-related hypermotor epilepsy: prevalence, impact and management strategies]===
*"Seizure frequency improved in a single patient with refractory ADSHE after nicotine transdermal patches treatment.(108) The favorable effect of nicotine on seizure frequency was also described in 9 of 22 patients from two European ADSHE families carrying CHRNA4 mutations.(109) Considering the role of the cholinergic system in arousal regulatory processes, these observations suggested a possible link between nicotine defect, alteration of arousal regulation and seizures in SHE/ADSHE patients. However, despite the reported positive effect of nicotine in reducing seizure frequency, a case–control family study, did not find a higher tendency to smoke tobacco in SHE patients and their relatives compared with the control cases.(110)
**Citation: Menghi V, Bisulli F, Tinuper P, Nobili L. Sleep-related hypermotor epilepsy: prevalence, impact and management strategies. Nat Sci Sleep. 2018 Oct 10;10:317-326. doi: 10.2147/NSS.S152624. PMID: 30349413; PMCID: PMC6186898.

===2015 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433466/ Pearls & Oy-sters: A case of refractory nocturnal seizures]===
*"Due to frequent seizures, there was a paucity of slow-wave sleep and complete absence of REM sleep. On the second day of her hospital admission, a 7-mg nicotine patch was applied about 2–3 hours before bedtime. There was almost complete resolution of clinical and electrical events. The duration of slow-wave sleep increased and REM sleep was recorded. The next morning, the patient felt refreshed and less anxious."
**Citation: Pavlakis PP, Douglass LM. Pearls & Oysters: A case of refractory nocturnal seizures: Putting out fires without smoke. Neurology. 2015 May 5;84(18):e134-6. doi: 10.1212/WNL.0000000000001539. PMID: 25941204; PMCID: PMC4433466.

===2012 [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2012.03715.x Resolution of epileptic encephalopathy following treatment with transdermal nicotine]===
*We report resolution of an epileptic encephalopathy by administration of transdermal nicotine patches in an adolescent with severe nonlesional refractory frontal lobe epilepsy. The 18.5‐year‐old female patient had refractory epilepsy from the age of 11. Recurrent electroencephalography (EEG) recordings showed mostly generalized activity, albeit with right frontal predominance. Almost all antiepileptic medications failed to provide benefit. She developed an encephalopathic state with cognitive decline. The nonlesional frontal lobe epilepsy and a family history of a cousin with nocturnal epilepsy with frontal origin suggested genetic etiology. Transdermal nicotine patches brought complete resolution of the seizures, normalization of the EEG, and a significant improvement in her thinking process and speech organization. Sequencing of the CHRNB2 and CHRNA4 genes did not detect a mutation. Transdermal nicotine patches should be considered in severe pharmacoresistant frontal lobe epilepsy.
*[https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03715.x PDF Version]
**Citation: Zerem, A., Nishri, D., Yosef, Y., Blumkin, L., Lev, D., Leshinsky‐Silver, E., Kivity, S. and Lerman‐Sagie, T. (2013), Resolution of epileptic encephalopathy following treatment with transdermal nicotine. Epilepsia, 54: e13-e15. doi: 10.1111/j.1528-1167.2012.03715.x

===2006 [https://pubmed.ncbi.nlm.nih.gov/16931165/ Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy]===
*"This study indicates that nicotine consumption is an environmental factor that, in many patients with ADNFLE, may influence susceptibility to seizures. A detailed account of tobacco habits should be part of the history. Transdermal nicotine should be considered in pharmacoresistant cases."
*[https://sci-hub.se/10.1016/j.yebeh.2006.07.008 PDF Full study]
**Citation: Brodtkorb E, Picard F. Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Behav. 2006 Nov;9(3):515-20. doi: 10.1016/j.yebeh.2006.07.008. Epub 2006 Aug 22. PMID: 16931165.

===2003 [https://onlinelibrary.wiley.com/doi/full/10.1046/j.1528-1157.2003.58102.x-i1?sid=nlm%3Apubmed Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study]===
*In this individual with refractory [[Special:MyLanguage/Abbreviations|'''ADNFLE''']], nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
*[https://sci-hub.st/https://doi.org/10.1046/j.1528-1157.2003.58102.x-i1 PDF Version]
**Citation: Willoughby, J.O., Pope, K.J. and Eaton, V. (2003), Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study. Epilepsia, 44: 1238-1240. doi: 10.1046/j.1528-1157.2003.58102.x-i1
 

='''Sepsis/Septic/endotoxemia/infection'''=
===2024 [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2014 [https://academic.oup.com/jid/article/209/10/1668/855517#78932729 Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation]===
*Animal study
*In conclusion, stimulation of α7nAChR by nicotine improves mortality rates and MODS during sepsis. This protective effect of nicotine can be associated with the inhibition of TLR4 overexpression through the PI3K/Akt signaling pathway. Although the therapeutic potential of nicotine is still limited by its nonspecific effects, this study may provide an impetus for further development of therapeutic strategies for modifying the cholinergic antiinflammatory pathway in the treatment of various inflammatory diseases.
**Citation: Kim TH, Kim SJ, Lee SM. Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation. J Infect Dis. 2014 May 15;209(10):1668-77. doi: 10.1093/infdis/jit669. Epub 2013 Dec 1. Erratum in: J Infect Dis. 2015 Mar 1;211(5):851. doi: 10.1093/infdis/jiu824. PMID: 24298024.
***Acknowledgement: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (NRF-2013R1A1A3008145).

===2011 [https://pubmed.ncbi.nlm.nih.gov/20805763/ Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide]===
*Animal Study
*The results suggested that both carbachol and nicotine play a role in the anti-inflammatory process and organ function protection through the α7 subunit of nicotinic cholinergic receptor.
*[https://sci-hub.st/10.1097/TA.0b013e3181e9732d PDF Full Paper]
**Citation: Zhou G, Hu S, Lv Y, Song Q, Zou X, Sheng Z. Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide. J Trauma. 2011 Jul;71(1):157-62. doi: 10.1097/TA.0b013e3181e9732d. PMID: 20805763.
***Acknowledgement: From the Laboratory of Shock and Organ Dysfunction (G.Z., S.H., Y.L., Q.S., X.Z., Z.S.), Burn Institute, the First Hospital Affiliated to the People’s Liberation Army General Hospital, Beijing, China.

===2005 [https://academic.oup.com/jid/article/191/12/2138/842542 The Cholinergic Anti-Inflammatory Pathway Regulates the Host Response during Septic Peritonitis]===
*Animal Study
*"Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired."
**Citation: van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis. 2005 Jun 15;191(12):2138-48. doi: 10.1086/430323. Epub 2005 May 10. PMID: 15898001.
***Acknowledgement: Financial support: Academic Medical Center, Amsterdam, The Netherlands. Potential conflicts of interest: K.J.T. is cofounder of Critical Therapeutics Inc., a pharmaceutical company developing potential future treatment modalities based on the cholinergic anti-inflammatory pathway.

='''Sleep'''=

==Apnea==

===1991: [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against sleep apnea (other diseases / issues mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1985: [https://pubmed.ncbi.nlm.nih.gov/3965253/ Nicotine: a different approach to treatment of obstructive sleep apnea]===
*Reduced upper airway muscle activity may contribute to the occurrence of obstructive apneas during sleep. There is no uniformly successful treatment of these apneas, and it is possible that agents which increase upper airway muscle activity could reduce the occurrence of obstruction during sleep. Nicotine, a known stimulant of breathing, also increases the activity of muscles which dilate the upper airway proportionally more than it does ventilation. Hence, we evaluated the effect of nicotine on apneas during the first two hours of sleep in eight patients with sleep apnea syndrome. It was concluded that nicotine reduces apneas during the early hours of sleep, and this effect may be caused by its stimulating action on upper airway muscles.
*[https://sci-hub.se/10.1378/chest.87.1.11 PDF Version]
**Citation: Gothe B, Strohl KP, Levin S, Cherniack NS. Nicotine: a different approach to treatment of obstructive sleep apnea. Chest. 1985 Jan;87(1):11-7. doi: 10.1378/chest.87.1.11. PMID: 3965253.
***Acknowledgement: None found

==REM==

===2017: [https://onlinelibrary.wiley.com/doi/10.1002/brb3.704 Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus]===
*Animal study
*MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein.
**Citation: Abd Rashid N, Hapidin H, Abdullah H, Ismail Z, Long I. Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus. Brain Behav. 2017; 7:e00704. https://doi.org/10.1002/brb3.704
***Acknowledgement: This study was supported by the Universiti Sains Malaysia (USM) Short-Term Grant Scheme (304/PPSK/61312093), USM Research University grants (RUI) (1001/PPSK/812139) and Fundamental Research Grant Scheme (FRGS) (203/PPSK/6171153).

===2011: [https://onlinelibrary.wiley.com/doi/10.1002/hipo.20806 Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat]===
*Animal Study
*However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.
*[https://www.academia.edu/18461315/Acute_nicotine_treatment_prevents_REM_sleep_deprivation_induced_learning_and_memory_impairment_in_rat PDF Full paper]
**Citation: Aleisa, A.M., Helal, G., Alhaider, I.A., Alzoubi, K.H., Srivareerat, M., Tran, T.T., Al-Rejaie, S.S. and Alkadhi, K.A. (2011), Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat. Hippocampus, 21: 899-909. https://doi.org/10.1002/hipo.20806
***Acknowledgement: None found
 

='''Smoking Cessation / Preventing Relapse'''=
===Resource Doc: [https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO - Myth of the month: Ecigs and snus don’t help smokers quit]===
*Links and conclusions of studies formatted to fit the character limits on Twitter

===[https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]===
*This wiki page shows over 70 studies demonstrating these products help people stop smoking.
 

='''Spinal Cord Injury'''=
===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
*Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
*Acknowledgements: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.
*Key words: spinal cord injury; nicotine; neuronal nicotinic receptors; oxidative stress; inflammatory responses; nitric oxide synthase

= Stroke =

=== 2025: '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf034/8005730?redirectedFrom=fulltext&login=false The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]''' ===

* Animal study (mice)
* These results demonstrate that nicotine treatment could alleviates the IS-compromised integrity of BBB by regulating the Wnt signal pathway through α7 nAChR.
* The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke.
* Qianqian Pang, Xinyang Yan, Zheng Chen, Liang Yun, Jiang Qian, Zeyi Dong, Miao Wang, Wei Deng, Yao Fu, Tao Hai, Zhichao Chen, Xianfang Rong: Nicotine & Tobacco Research, ntaf034, <nowiki>https://doi.org/10.1093/ntr/ntaf034</nowiki>

='''Tobacco Use Disorder'''=

===2023: [https://link.springer.com/article/10.1007/s11606-023-08137-z Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===
*The remarkable decline in cigarette smoking since 1964 has plateaued; approximately 12.5% of Americans still smoke. People who continue to smoke are largely members of marginalized groups, such as people with behavioral health conditions (BHC), encompassing both mental health and substance use disorders.
*Although not a panacea, electronic cigarettes may represent a powerful harm reduction tool amongst subpopulations traditionally left behind in conventional smoking cessation movements. The argument in favor of studies of electronic cigarettes as a smoking cessation, harm reduction intervention in people with BHC is multi-faceted. People with BHC have higher levels of smoking burdens and nicotine addiction compared to the general population, and they quit at lower rates. Unlike NRT, the nicotine delivery from an electronic cigarette mimics the nicotine pharmacokinetics of tobacco cigarettes unaccompanied by high levels of toxicants and carcinogens.22 Thus, electronic cigarettes may be well positioned to satisfy this nicotine addiction, and mitigate the intense nicotine withdrawal symptoms that sabotage many quit attempts. People with BHC want to stop smoking, and indicators suggest that electronic cigarettes would be an acceptable and well-received intervention.
**Citation: Vuong, J.T., Ruedisueli, I., Beaudin, C.S. et al. Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders. J GEN INTERN MED 38, 1970–1974 (2023). https://doi.org/10.1007/s11606-023-08137-z
***Acknowledgement: None stated

='''Tourette's Syndrome'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012 [https://pubmed.ncbi.nlm.nih.gov/22776623/ Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond]===
* The article presents a mini-review of studies on TS and depression over the past 25 years.
* It summarizes the studies on the behavioral biology of the basal ganglia and its neurotransmitters.
* It describes research with TS patients to evaluate the therapeutics of nicotine and mecamylamine.
* [https://sci-hub.se/10.1016/j.physbeh.2012.06.023 PDF Version]
*Citation: Sanberg, P. R., Vindrola-Padros, C., & Shytle, R. D. (2012). Translating laboratory discovery to the clinic: From nicotine and mecamylamine to Tourette’s, depression, and beyond. Physiology & Behavior, 107(5), 801–808. doi:10.1016/j.physbeh.2012.06.023
*Acknowledgement: Paul R. Sanberg and R. Douglas Shytle are inventors on patents related to technology described herein and licensed from the University of South Florida to Targacept, Inc. Because of the historical nature of this article, the authors included a number of self-citations required for a chronological discussion.

===2004 [https://pubmed.ncbi.nlm.nih.gov/15132126/ Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome]===
*In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 hours, but counteracted [https://en.wikipedia.org/wiki/P300_(neuroscience) ERP-P300] signs of diminished attention seen 2 weeks following placebo treatment.
*Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention.
*[https://sci-hub.st/10.1016/j.eurpsy.2003.11.002 PDF Version ]
*Citation: Howson, A. L., Batth, S., Ilivitsky, V., Boisjoli, A., Jaworski, M., Mahoney, C., & Knott, V. J. (2004). Clinical and attentional effects of acute nicotine treatment in Tourette’s syndrome. European Psychiatry, 19(2), 102–112. doi:10.1016/j.eurpsy.2003.11.002
*Acknowledgement: This study was supported with a grant from the Tourette Syndrome Association (USA), and patient recruitment was aided by the Ottawa chapter of the Tourette Syndrome Foundation of Canada.

===2001 [https://pubmed.ncbi.nlm.nih.gov/11681767/ Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study]===
*[[Special:MyLanguage/Abbreviations|'''Transdermal nicotine (TNP)''']] was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder
*[https://www.researchgate.net/profile/Paul_Sanberg/publication/11670769_Transdermal_Nicotine_and_Haloperidol_in_Tourette's_Disorder/links/5be32624299bf1124fc2d86a/Transdermal-Nicotine-and-Haloperidol-in-Tourettes-Disorder.pdf PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Wilkinson BJ, McConville B, Sanberg PR. Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study. J Clin Psychiatry. 2001 Sep;62(9):707-14. doi: 10.4088/jcp.v62n0908. PMID: 11681767.

===1997 [https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994 Nicotine for the treatment of Tourette's syndrome]===
*Within 24 hr of the application of a single 7-mg [[Special:MyLanguage/Abbreviations|'''TNP (nicotine patch)''']], the severity and frequency of tic symptoms is significantly decreased over baseline. This response is rapid, often reaching its maximum in the first 3 hr after application of a single patch. The duration of therapeutic effect of a single 7-mg TNP is variable and may last for about l-2 weeks.
*Application of a 7-mg TNP to children and adolescents with [[Special:MyLanguage/Abbreviations|'''TS''']] appears to be clinically safe, with transient side effects. However, no child under 8 years of age and weighing less than 25 kg was considered for TNP treatment.
*[https://sci-hub.st/https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994?via%3Dihub PDF Version]
*Citation: Paul R. Sanberg, Archie A. Silver, R.Doug Shytle, Mary Katherine Philipp, David W. Cahill, Harold M. Fogelson, Brian J. McConville, Nicotine for the treatment of Tourette's syndrome, Pharmacology & Therapeutics, Volume 74, Issue 1, 1997, Pages 21-25, ISSN 0163-7258, doi.org/10.1016/S0163-7258(96)00199-4.
* Acknowledgements-This review was supported, in part, by grants from the Tourette Syndrome Association, The National Institute of Neurological Disease and Stroke (ROl NS 32067sOlAl) and the Smokeless Tobacco Research Council.
*Keywords: Nicotine; Tourette's syndrome; tics; neuropsychiatric disorders

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Gilles de la Tourette’s syndrome (TS)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

=== 1996 [https://pubmed.ncbi.nlm.nih.gov/8973070/ Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome]===
* Sixteen Tourette's syndrome patients, aged 9 to 15 years, whose symptoms were not controlled with neuroleptics, were followed for various lengths of time after the application of one 7 mg [[Special:MyLanguage/Abbreviations|'''transdermal nicotine patch (TNP)''']] for 24 hours. While there was a broad range in individual response, application of the TNP produced significant reductions in [[Special:MyLanguage/Abbreviations|'''Yale Global Tic Severity Scale (YGTSS)''']] scores relative to baseline, with an average duration of effect lasting between 1 and 2 weeks. Side effects, for the most part, were transient.
*Eleven patients had greater percentage changes after the second TNP than after the first TNP
*[https://sci-hub.st/10.1097/00004583-199612000-00015 PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Sanberg PR. Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1996 Dec;35(12):1631-6. doi: 10.1097/00004583-199612000-00015. PMID: 8973070.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1643197/ The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder]===
*In this study, nicotine markedly potentiated haloperidol effects in treating [[Special:MyLanguage/Abbreviations|'''TD''']], and showed lesser effects on TD when used alone.
*[https://sci-hub.st/10.1016/0006-3223(92)90315-q PDF Version]
* Citation: McConville BJ, Sanberg PR, Fogelson MH, King J, Cirino P, Parker KW, Norman AB. The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder. Biol Psychiatry. 1992 Apr 15;31(8):832-40. doi: 10.1016/0006-3223(92)90315-q. PMID: 1643197.
*Acknowledgements: Supported in part by grants from the Smokeless Tobacco Research Council, Inc., the Tourette Syndrome Association, and Merrell Dow Pharmaceuticals. The authors thank Roger Stuebing, B.S.M.E., M.S.I.E., and Sunny Y. Lu, M.D., Ph.D. for statistical advice and Merrell Dow Pharmaceuticals for supplying both Nicoreue® gum and placebo nicotine gum.

='''Weight Loss / Appetite Control / Metabolism / Obesity'''=

===2024 Article [https://web.archive.org/web/20241204102835/https://tobaccoreporter.com/2024/12/03/slim-chances/ Harm reduction, smoking cessation and weight]====
*"Nicotine influences eating and weight in multiple ways, from hormones to microbiomes to taste perceptions. The bottom line: Nicotine raises the metabolic rate while also depressing appetite."

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
**Citation: Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database of Systematic Reviews 2021, Issue 10. Art. No.: CD006219. DOI: 10.1002/14651858.CD006219.pub4. Accessed 03 July 2025.
***[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/information Acknowledgement]

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.
*Low-grade inflammation is a key feature of obesity and links obesity to insulin resistance, impaired glucose tolerance and even diabetes.
*Overall, these findings suggest that nicotine and specific α7nAChR agonists may be beneficial in the prevention and treatment of obesity-induced inflammation and insulin resistance. However, there is also evidence that heavy smoking affects body fat distribution that is associated with central obesity and insulin resistance. Moreover, smoking appears to aggravate insulin resistance in persons with type 2 diabetes and to impair glycemic control.
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in reduction of body weight
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Suggested additions to this page'''=

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.

===2925: [https://link.springer.com/article/10.1186/s12890-025-04071-4 Modulatory roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats]===

===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===
*[https://sci-hub.st/10.1007/s12640-021-00375-5 PDF Full paper]

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

===[https://www.researchgate.net/publication/325159226_Resolution_of_chronic_rhinitis_to_staphylococcus_aureus_in_a_non-smoker_who_started_to_use_glycerine_based_e-cigarettes_Antibacterial_effects_of_vaping Resolution of chronic rhinitis to staphylococcus aureus in a non-smoker who started to use glycerine based e-cigarettes: Antibacterial effects of vaping?]===

===2019: [https://medium.com/parkinsons-uk/protecting-brain-cells-the-story-of-nicotine-b3b51f5b8259 Protecting brain cells — the story of nicotine]===
*[https://web.archive.org/web/20221021040501/https://www.parkinsons.org.uk/nicotine-good-bad-and-ugly Nicotine - Good, Bad, Ugly]

===2018: [https://pubmed.ncbi.nlm.nih.gov/29770521/ Nicotine-mediated neuroprotection of rat spinal networks against excitotoxicity]===

===2017 [https://www.ncbi.nlm.nih.gov/pubmed/27940486 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
*different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German) 'Cognition: nicotine versus neuropsychiatric disorders' ===

===Dr. Newhouse [http://mindstudy.org/news Mind Study]===

===2010 [https://pubmed.ncbi.nlm.nih.gov/20414766/ Meta-analysis of the acute effects of nicotine and smoking on human performance] and 2012 [https://n.neurology.org/content/78/2/91.short Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*Clinical studies suggest some cognitive improvements as a result of nicotine.

===2021 [https://www.dovepress.com/effectiveness-and-safety-profile-of-alternative-tobacco-and-nicotine-p-peer-reviewed-fulltext-article-JMDH Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review]===

===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].”
https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===

===To do: Go through the references for nicotine related studies===
====2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]====

===1989 [https://www.sciencedirect.com/science/article/abs/pii/002432058990444X?via%3Dihub Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders]===
*Chewing nicotine gum produced striking relief from tics and other symptoms of Tourette syndrome not controlled by neuroleptic treatment alone. It appears that the use of nicotine or cannabinoids may greatly improve the clinical response to neuroleptics in motor disorders.
*[https://sci-hub.st/https://doi.org/10.1016/0024-3205(89)90444-X PDF Version]
*Citation: D.E. Moss, Patricia Z. Manderscheid, S.P. Montgomery, Andrew B. Norman, Paul R. Sanberg, Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders, Life Sciences, Volume 44, Issue 21, 1989, Pages 1521-1525, ISSN 0024-3205, doi.org/10.1016/0024-3205(89)90444-X.
*Acknowledgements: Supported in part by NIMH (RR 08012) and NIDA. Levonantradol and fluphenazine HCL were generous gifts from Pfizer Pharmaceuticals (Groton, Conn.) and E.R. Squibb and Sons (Princeton, N.J.), respectively.

===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

===[https://www.researchgate.net/publication/325159226_Resolution_of_chronic_rhinitis_to_staphylococcus_aureus_in_a_non-smoker_who_started_to_use_glycerine_based_e-cigarettes_Antibacterial_effects_of_vaping Resolution of chronic rhinitis to staphylococcus aureus in a non-smoker who started to use glycerine based e-cigarettes: Antibacterial effects of vaping?]===

===2019: [https://medium.com/parkinsons-uk/protecting-brain-cells-the-story-of-nicotine-b3b51f5b8259 Protecting brain cells — the story of nicotine]===
*[https://web.archive.org/web/20221021040501/https://www.parkinsons.org.uk/nicotine-good-bad-and-ugly Nicotine - Good, Bad, Ugly]

===2017 [https://www.ncbi.nlm.nih.gov/pubmed/27940486 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
*different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German) 'Cognition: nicotine versus neuropsychiatric disorders' ===

===Dr. Newhouse [http://mindstudy.org/news Mind Study]===

===2010 [https://pubmed.ncbi.nlm.nih.gov/20414766/ Meta-analysis of the acute effects of nicotine and smoking on human performance] and 2012 [https://n.neurology.org/content/78/2/91.short Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*Clinical studies suggest some cognitive improvements as a result of nicotine.

===2021 [https://www.dovepress.com/effectiveness-and-safety-profile-of-alternative-tobacco-and-nicotine-p-peer-reviewed-fulltext-article-JMDH Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review]===

===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].”
https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===

===To do: Go through the references for nicotine related studies===
====2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]====

='''More Information'''=

*[[Special:MyLanguage/Nicotine Studies|'''List of researchers''']] studying nicotine / tobacco harm reduction

*If you'd prefer someone else to add a study to a topic, there is a "topic" called "Suggested studies to add to this page". You may put the link in that section for one of the regular page editors to address.

*'''PAGE EDITORS - Please only add Studies, Surveys, Papers in this format to keep page consistent for all viewers.'''
**Topic
**Note here if animal study (leave blank if not)
**Year (list new to old) Name of Study (In link format to the study)
**Brief Summary
**Link to PDF Version
**Citation
**Acknowledgements (funded by, helped by)
**Keywords
**Other
[[Category:Studies, Surveys, and Papers]]
[[Category:THR product]]
[[Category:THR Stories]]

Nicotine therapeutic benefits

2026-04-04T16:08:04Z

Skip: /* Suggested additions to this page */

<big>'''''Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that fewer people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine. Some of these studies show a potential benefit, not proof of a benefit. Some of the studies are animal studies, not human studies.'''''</big>
 
 
[[File:Nic Ther Ben.png|alt=Nicotine Therapeutic benefits banner|center]]
 

 

<big>'''Note: Some topics are subgroups under the main topic of "Mental Health." '''</big>
 

='''Acne'''=

===2010 [https://ijphjournal.it/article/view/5708 Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies]===
*Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis.
*Our meta-analysis underlines that there is no evidence to support an association between smoking habits and acne, although in three of the good quality papers a significant protection in the current smoker was found. It necessary to be cautious in declaring that smoking may provide a protective effect in the pathogenesis of acne because the analysis was based on only a small number of studies.

===2006 [https://www.sciencedirect.com/science/article/pii/S0022202X15330153 Severe Acne Vulgaris and Tobacco Smoking in Young Men]===
*It is crucial to emphasize that any positive effects found must be traced to specific tobacco components that can be therapeutically used without smoking (e.g., nicotine patches or gums), to avoid any “legitimatizing” of smoking based on its beneficial effects on health.
*Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P=0.0078).
*Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

===1993 [https://academic.oup.com/ced/article-abstract/18/2/100/6629365 Does smoking influence acne?]===
*[https://sci-hub.se/10.1111/j.1365-2230.1993.tb00986.x PDF of full study]
*The findings of this study support the hypothesis that some component of cigarette smoke, possibly nicotine, has an anti‐inflammatory action on acne.
 

='''ADD / ADHD / Attention / Cognition'''=

=== 2025 '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf060/8078909 Nicotine improves working memory via augmenting BDNF levels through α7 nAChR: evidence from clinical and pre-clinical studies]''' ===

* While smoking has been associated with many negative consequences to human health, one possible benefit is that nicotine could improve cognitive functions. Previous studies have suggested that smoking may influence brain-derived neurotrophic factor (BDNF) levels.
* Our research revealed that tobacco product use led to an increase in working memory and human plasma BDNF levels. Furthermore, nicotine was responsible for the elevation in BDNF levels, which showed dose-dependent increases in both serum and the hippocampus, and improved memory performance.
* Animal study (rat)
* ''Yingyan Li, PhD, Xin Li, Yaning Fu, PhD, Wenjun Mou, Zuxin Chen, PhD, Ping Wu, PhD, Fanglin Liu, PhD, Huan Chen, PhD, Hongwei Hou, PhD, Qingyuan Hu, PhD: Nicotine & Tobacco Research'', ntaf060, <nowiki>https://doi.org/10.1093/ntr/ntaf060</nowiki>

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.845646/full Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms]===
*"Our review of evidence supports the finding that individuals with ADHD are at greater vulnerability for both initiation and continuation of smoking (both cigarettes, e-cigarettes)."
*"Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes."
*Taylor, M. R., Carrasco, K., Carrasco, A., & Basu, A. (2022). Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms. Frontiers in Neuroscience, 16, 845646. https://doi.org/10.3389/fnins.2022.845646
*Funds for open access publication fees are contributed by the Faculty of Health, University of Canterbury and University of Canterbury library.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*High rates of smoking are observed among individuals with psychiatric disorders including schizophrenia, bipolar disorder, major depression, attention deficit hyperactivity disorder (ADHD) and comorbid substance use disorders (SUD). Because these psychiatric disorders are associated with various cognitive impairments, including deficits in attention, working memory, and response inhibition functions, the cognitive enhancing effects of nicotine may be especially important determinants of the initation and maintenance of smoking in this comorbid population. Growing evidence suggest that cognitive enhancing effects of nicotine may also contribute to the difficulty in quitting smoking, especially in individuals with psychiatric disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.tandfonline.com/doi/full/10.1080/10826084.2017.1334066 Causal Factors of Increased Smoking in ADHD: A Systematic Review]===
*One of the most striking comorbidities of ADHD is nicotine dependence. Youth diagnosed with ADHD are 2–3 times more likely to smoke than their peers without ADHD, initiate smoking earlier in life and progress more quickly and more frequently to regular use and dependence. Possible explanations for these increased risks are: (a) self-medication of ADHD symptoms with the stimulant nicotine; (b) ADHD symptoms like inattention and hyperactivity/impulsivity predispose for smoking initiation and impede smoking cessation; (c) peer pressure; and/or (d) common genetic or environmental determinants for ADHD and smoking.
*In contrast, the positive relation between ADHD and nicotine dependence is currently best explained by the self-medication hypothesis. This hypothesis has a clear pharmacological rationale and is supported by ample evidence, but awaits confirmation from longitudinal naturalistic studies.
*Citation: Jan van Amsterdam, Bauke van der Velde, Mieke Schulte & Wim van den Brink (2018) Causal Factors of Increased Smoking in ADHD: A Systematic Review, Substance Use & Misuse, 53:3, 432-445, DOI: 10.1080/10826084.2017.1334066

===2014: [https://www.medscape.com/viewarticle/827544_1 Adult Attention-Deficit/Hyperactivity Disorder and Nicotine Use: A Qualitative Study of Patient Perceptions]===
*Participants had different views about the link between cigarette smoking and ADHD. While the majority thought of nicotine as a sort of therapy, viewing smoking as a way to self-medicate symptoms of ADHD, motivations for nicotine use were also related to self-image, desire to belong to a peer-group, and a drive to undermine perceived social norms. Ultimately, these findings can be used by clinicians to improve treatment alliance and collaboration.
*[https://sci-hub.se/10.1186/1471-244x-14-141 Alternative Link]
*Citation: Liebrenz, M., Frei, A., Fisher, C. E., Gamma, A., Buadze, A., & Eich, D. (2014). Adult attention-deficit/hyperactivity disorder and nicotine use: a qualitative study of patient perceptions. BMC Psychiatry, 14(1). doi:10.1186/1471-244x-14-141

===2011 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353150/ Cognitive enhancers for the treatment of ADHD]===
*Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting approximately 8–9% of school-aged children and 4–5% of adults (Froehlich et al., 2007; Kessler et al., 2006; Visser et al., 2007). Although formally the disorder is characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity (APA, 2000), myriad phenotypic features—many of which are related to cognition broadly defined—have been shown to distinguish those with ADHD from those without the disorder.
*Together, these findings have led to the hypothesis that individuals with ADHD may smoke in order to alleviate requisite symptoms of the disorder and further suggest nicotine and/or nicotinic agonists can be used to improve aspects of cognitive function in these patients (McClernon and Kollins, 2008). Some support for this hypothesis has been provided by studies which have shown positive effects of nicotine on ADHD symptoms (Gehricke et al., 2009; Shytle et al., 2002) and cognitive performance (Levin et al., 1996; Potter and Newhouse, 2004) in non-smokers with ADHD. Whereas there are currently no FDA-approved nicotinic agonists to treat ADHD, laboratory and small-scale clinical trials have been conducted in recent years, and novel nicotinic pharmacotherapies are on the horizon.
*Citation: Bidwell LC, McClernon FJ, Kollins SH. Cognitive enhancers for the treatment of ADHD. Pharmacol Biochem Behav. 2011 Aug;99(2):262-74. doi: 10.1016/j.pbb.2011.05.002. Epub 2011 May 10. PMID: 21596055; PMCID: PMC3353150.

===2009 [https://pubmed.ncbi.nlm.nih.gov/20025370/ Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder]===
*Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.
*Citation: Gehricke, J. G., Hong, N., Whalen, C. K., Steinhoff, K., & Wigal, T. L. (2009). Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors, 23(4), 644–655. https://doi.org/10.1037/a0017441

===2009 [https://www.tandfonline.com/doi/abs/10.3109/15622970209150616 A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder]===
*All 10 subjects enrolled (six males, four females; mean age = 10 years, SEM = 0.8) completed the study. As assessed by the 48-item Conners Parent Rating Scale at endpoint and during the trial, there was a significantly greater reduction in ADHD symptoms on “Learning Problems” and “Hyperactivity” subfactors. Nausea, stomach ache, itching under patch and dizziness were the most frequently reported adverse effects associated with transdermal nicotine.
*Citation: R. Douglas Shytle, Archie A. Silver, Berney J. Wilkinson & Paul R. Sanberg (2002) A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder, The World Journal of Biological Psychiatry, 3:3, 150-155, DOI: 10.3109/15622970209150616

===2008 [https://www.sciencedirect.com/science/article/abs/pii/S0091305707003048?via%3Dihub Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to [[Special:MyLanguage/Abbreviations|'''ADHD''']].
*[https://sci-hub.st/https://doi.org/10.1016/j.pbb.2007.09.014 PDF Version]
*Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.
*Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.

===2008 [https://pmc.ncbi.nlm.nih.gov/articles/PMC2446482/ Transdermal Nicotine in Adult ADHD With Depression and Anxiety]===
*"This case report neither rules out the placebo effect, nor does it prove that transdermal nicotine is useful in managing adult ADHD with depression and anxiety. However, it does suggest that the beneficial effect of transdermal nicotine may be attributed to biobehavioral pathways common to chronic nicotine withdrawal and ADHD with depression and anxiety. Nicotine agonists and delivery systems may be new treatments for adult ADHD. Larger well-designed studies are warranted to evaluate the therapeutic potential of nicotine delivery systems in otherwise medically stable adults with ADHD accompanied by depression and anxiety. Further exploration of the nicotinic-cholinergic system may also expand our understanding of the neuropsychiatry underlying ADHD."
*Citation: Cocores JA. Transdermal nicotine in adult ADHD with depression and anxiety. Prim Care Companion J Clin Psychiatry. 2008;10(3):253-4. doi: 10.4088/pcc.v10n0312f. PMID: 18615164; PMCID: PMC2446482.
*Dr. Cocores reports no financial affiliations or other relationships relevant to the subject of this letter.

===2007 [https://www.academia.edu/2412620/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
*The data from diverse studies are generally consistent with the self-medication hypothesis and suggest that individuals with ADHD may smoke to alleviate symptoms associated with attention deficit, impulsivity, and hyperactivity. More studies on larger samples are necessary to assess the differential risks for adolescent smoking initiation that are associated with ADHD subtypes and with ODD and CD comorbidities.
*Citation: Gehricke, J.-G., Loughlin, S., Whalen, C., Potkin, S., Fallon, J., Jamner, L., … Leslie, F. (2007). Smoking to self-medicate attentional and emotional dysfunctions. Nicotine Tobacco Research, 9, 523–536. https://doi.org/10.1080/14622200701685039

===2007: [https://pubmed.ncbi.nlm.nih.gov/18022679/ Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.
**Citation: Potter AS, Newhouse PA. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav. 2008 Feb;88(4):407-17. doi: 10.1016/j.pbb.2007.09.014. Epub 2007 Sep 26. PMID: 18022679.
***Acknowledgement: Paywalled, unable to access.

===2006 [https://www.academia.edu/17983526/The_reinforcing_effects_of_nicotine_and_stimulant_medication_in_the_everyday_lives_of_adult_smokers_with_ADHD_A_preliminary_examination The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination]===
*The findings suggest that smokers with ADHD experience nicotine-related reductions in ADHD symptoms during their everyday lives.
*Citation: Gehricke, J. G., Whalen, C., Jamner, L., Wigal, T., & Steinhoff, K. (2006). The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination. Nicotine Tobacco Research, 8(1), 37–47. https://doi.org/10.1080/14622200500431619

===2006 [https://www.sciencedirect.com/science/article/abs/pii/S0031938405005627?via%3Dihub Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits]===
*The results showed nicotine-induced improvement on some measures of sustained attention in the low attention group and some decrement in working memory in the high attention group, which suggests that nicotine tends to optimize rather than improve performance on cognitive tasks.
*[https://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]
*Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2003: [https://www.academia.edu/2412608/Is_There_a_Link_Between_Adolescent_Cigarette_Smoking_and_Pharmacotherapy_for_ADHD Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?]===
*Self-report surveys, electronic diaries, and salivary cotinine all indicated that adolescents treated with pharmacotherapy for ADHD smoked less than their untreated counterparts over 2 years of high school. These convergent findings from 3 disparate indicators lend support to the self-medication hypothesis over the gateway hypothesis, although alternative explanations need further study. The findings also suggest that early treatment of psychological and behavioral problems may prevent or delay smoking initiation
*Citation: Whalen, C. K., Jamner, L. D., Henker, B., Gehricke, J.-G., & King, P. S. (2003). Is There a Link Between Adolescent Cigarette Smoking and Pharmacotherapy for ADHD? Psychology of Addictive Behaviors, 17(4), 332–335. https://doi.org/10.1037/0893-164X.17.4.332

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===2001 [https://psycnet.apa.org/record/2001-14365-012 Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder.]===
*This small study (40 participants) provided evidence that nicotine treatment can reduce severity of attentional deficit symptoms and produce improvement on an objective computerized attention task.
*Citation: Levin, E. D., Conners, C. K., Silva, D., Canu, W., & March, J. (2001). Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Experimental and Clinical Psychopharmacology, 9(1), 83–90. https://doi.org/10.1037/1064-1297.9.1.83

===1998 [https://pubmed.ncbi.nlm.nih.gov/9860103/ Transdermal nicotine effects on attention]===
*This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult non-smokers.
*[https://sci-hub.st/10.1007/s002130050750 PDF Version]
*Citation: Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J, Rose JE. Transdermal nicotine effects on attention. Psychopharmacology (Berl). 1998 Nov;140(2):135-41. doi: 10.1007/s002130050750. PMID: 9860103
*Acknowledgement: The authors thank R.J. Reynolds for financial support of the project. Work on this article was partially supported by Career Science Award (K05MH0122903) to Dr. Conners and Research Scientist Development Award (K02MH0098102) to Dr. March

===1996 [https://pubmed.ncbi.nlm.nih.gov/8741955/ Nicotine effects on adults with attention-deficit/hyperactivity disorder]===
*Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clinical trials with ADHD.
*[https://sci-hub.st/10.1007/BF02246281 PDF Version]
*Citation: Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl). 1996 Jan;123(1):55-63. doi: 10.1007/BF02246281. PMID: 8741955.
*Acknowledgement: The authors thank Dr. Allen Frances, Chairman of the Department of Psychiatry, Duke University Meidcal Center for his finanical support of the project. Work on this article was partially supported by Career Science Award (K05MH01229-03) to Dr. Conners and Research Scientist Development Award (K20MH00981-02) to Dr. March and a Young Investigator Award from the National Alliance for Research Schizophenia and Depression to Dr. Levin.

===1996: [https://pubmed.ncbi.nlm.nih.gov/8927677/ Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD)]===
*The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.
*Citation: Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull. 1996;32(1):67-73. PMID: 8927677.

===Year Unknown: Article: [https://www.adxs.org/en/page/192/nicotine-as-a-medication-for-adhd Nicotine as a medication for ADHD]===
*Lists references

 

='''Aging'''=

===2023: [https://www.nature.com/articles/s41467-023-36543-8 Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity]===
*Abstract "Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms."
**Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8
***Acknowledgement: This work was supported by grants from Shenzhen Science and Technology Program (KQTD20210811090117032), Shenzhen Key Laboratory of Viral Vectors for Biomedicine (ZDSYS20200811142401005), CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024) and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).

='''Akathisia'''=

===1997: [https://pubmed.ncbi.nlm.nih.gov/9399378/ Treatment of neuroleptic-induced akathisia with nicotine patches]===
*We administered 14 mg nicotine patches to 16 patients, all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia.
*[https://sci-hub.se/10.1007/s002130050436 PDF Version]
**Citation: Anfang MK, Pope HG Jr. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl). 1997 Nov;134(2):153-6. doi: 10.1007/s002130050436. PMID: 9399378.
 

='''Alcohol Use Disorder'''=

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

='''Allergies / Hayfever / Histamines''' (See also: Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis)=

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203434/ Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation]===
*Animal Study
*In this study, the effect of environmental tobacco smoke (ETS) on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated.
*In summary, ETS suppressed allergen-induced nasal responses including NHR by inhibiting allergen-specific Th2 cell responses. Although our present findings do not deny harmful effects of cigarette smoking, nicotine as a component of ETS may be a target to treat Th2-mediated allergic diseases, including allergic rhinitis (AR).
**Citation: Nishimura T, Kaminuma O, Saeki M, Kitamura N, Mori A, Hiroi T. Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation. Asia Pac Allergy. 2020 Apr 27;10(2):e18. doi: 10.5415/apallergy.2020.10.e18. PMID: 32411583; PMCID: PMC7203434.
***Acknowledgement: This work was supported in part by funding from the Smoking Research Foundation provided to Osamu Kaminuma.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440386/ Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium]===
*Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
**Citation: Skaaby T, Taylor AE, Jacobsen RK, et al. Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Sci Rep. 2017 May 22;7(1):2224. doi: 10.1038/s41598-017-01977-w. PMID: 28533558; PMCID: PMC5440386.
***Acknowledgement: This work was supported by the Medical Research Council (grant numbers: MR/J01351X/1, MC_UU_12013/6). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

===2014: [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085888 Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model]===
*Animal study
*In this study, nicotine treatment significantly ameliorated FA [Food Allergy], mainly due to the suppression of upregulated mucosal immune responses via α7 nAChRs on immune cells. Therefore, the therapeutic effects of nicotine and GTS-21 on the FA model raise the possibility that a strategy for drug discovery against FA by targeting α7 nAChRs could potentially have therapeutic benefits.
**Citation: Yamamoto T, Kodama T, Lee J, Utsunomiya N, Hayashi S, Sakamoto H, Kuramoto H, Kadowaki M. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS One. 2014 Jan 16;9(1):e85888. doi: 10.1371/journal.pone.0085888. PMID: 24454942; PMCID: PMC3894205.

===2008: [https://journals.aai.org/jimmunol/article/180/11/7655/84640/Nicotine-Primarily-Suppresses-Lung-Th2-but-Not Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens]===
*Animal Study
*hese results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia, mucous production, and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
**Citation: Neerad C. Mishra, Jules Rir-sima-ah, Raymond J. Langley, Shashi P. Singh, Juan C. Peña-Philippides, Takeshi Koga, Seddigheh Razani-Boroujerdi, Julie Hutt, Matthew Campen, K. Chul Kim, Yohannes Tesfaigzi, Mohan L. Sopori; Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens1. J Immunol 1 June 2008; 180 (11): 7655–7663. https://doi.org/10.4049/jimmunol.180.11.7655
***Acknowledgement: This work was supported in part by grants from the National Institutes of Health (R01-DA017003, R01-DA04208-15, and R01-DA042087S).

===2004: [https://link.springer.com/article/10.1007/s00011-004-1249-1 The effect of nicotine on basophil histamine release]===
*This study has demonstrated that nicotine agonists inhibit histamine release from human basophils.
*[https://sci-hub.st/10.1007/s00011-004-1249-1 PDF Full Version]
**Citation: Thompson-Cree, M.E.M., Stevenson, M.R., Shields, M.D. et al. The effect of nicotine on basophil histamine release. Inflamm. res. 53, 211–214 (2004). https://doi.org/10.1007/s00011-004-1249-1

='''Alzheimer / Dementia / Mild Cognitive Imparement (MCI)'''=
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

===2013 [https://link.springer.com/article/10.1007/s12017-013-8242-1 Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation]===
*Animal Study
*Taken together, these results demonstrate that nicotine prevents memory deficits and synaptic impairment induced by Aβ oligomers. In addition, nicotine improves memory in young APP/PS1 transgenic mice before extensive amyloid deposition and senile plaque development, and also in old mice where senile plaques have already formed.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/s12017-013-8242-1 PDF Version]
*Citation: Inestrosa, N.C., Godoy, J.A., Vargas, J.Y. et al. Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation. Neuromol Med 15, 549–569 (2013). doi: 10.1007/s12017-013-8242-1
*Acknowledgements: We thank Dr. Rodrigo Varas for his help with the electrophysiological studies of the α7-nAChR. This work was supported by a grant from FONDECYT No 120156 to N.C.I; predoctoral fellowships from CONICYT to G.G.F., M.S.A. F.G.S., J.A.R. and from Fundación Gran Mariscal de Ayacucho to J.Y.V. The Basal Center of Excellence in Science and Technology CARE was funded by CONICYT/PFB 12/2007.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/ Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment.
*Safety and tolerability for transdermal nicotine were excellent.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466669/pdf/znl91.pdf PDF Version]
*Citation: Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology. 2012 Jan 10;78(2):91-101. doi: 10.1212/WNL.0b013e31823efcbb. PMID: 22232050; PMCID: PMC3466669.

===2010 [https://www.tandfonline.com/doi/abs/10.1080/13607860220126808 Nicotine's effect on neural and cognitive functioning in an aging population]===
*Recent advances in nicotine research have pointed to a number of cognitive and neurological benefits that have been linked to the ingestion of nicotine.
*This article examines cognitive decline in the elderly and looks at nicotine's potential role in ameliorating this decline.
*Nicotine’s effects on cognitive functioning have shown it to increase perception, visual attention,and arousal as well as improving the speed and accuracy of motor functioning while decreasing reaction time and inhibiting declines in efficiency. In addition, research has shown nicotine to improve long-term and short-term memory, and to increase the ability to withhold inappropriate responses.
*Research has revealed that chronic exposure to nicotine produces an unusual up-regulation of the nicotinic receptor sites. This increase in receptor sites is thought to provide some protection against neuro-degenerative disorders such as Alzheimer’s disease.
*[https://sci-hub.st/10.1080/13607860220126808 PDF Version]
*Citation: K. N. Murray & N. Abeles (2002) Nicotine's effect on neural and cognitive functioning in an aging population, Aging & Mental Health, 6:2, 129-138, DOI: 10.1080/13607860220126808

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783.
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12436427/ Nicotinic receptors in aging and dementia]===
*Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects.
*Acute nicotine administration can improve performance of patients with AD on cognitive tasks, including verbal learning and memory, attention in a continuous performance task, and accuracy in a visual attention task.
*In addition to its ability to reverse cognitive deficits following aging, nicotine has been shown to protect against neurotoxic insult in vitro and in vivo. This suggests that nicotine has a dual effect on brain function following aging or injury, such that it can rescue function of remaining neurons, as well as saving neurons that might otherwise undergo cell death.
*[https://sci-hub.st/10.1002/neu.10102 PDF Version]
*Citation: Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. J Neurobiol. 2002 Dec;53(4):641-55. doi: 10.1002/neu.10102. PMID: 12436427.
*Keywords: nAChR; neuroprotection; Alzheimer’s disease; Parkinson’s disease; acetylcholine

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Alzheimer's disease (AD)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1410164/ Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease]===
*Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds).
*[https://sci-hub.st/10.1007/BF02247426 PDF Version]
*Citation: Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology (Berl). 1992;108(4):485-94. doi: 10.1007/BF02247426. PMID: 1410164.
*Acknowledgements. This research was supported by British-American Tobacco Co. Ltd. BJS thanks the Wellcome Trust and the Eleanor Peel Foundation for support.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in enhancement of performance, and protection against Alzheimer's disease (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1989 [https://pubmed.ncbi.nlm.nih.gov/2597885/ The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type]===
*Nicotine in patients with dementia of the Alzheimer type (DAT) produced a significant and marked improvement in discriminative sensitivity and reaction times on a computerised test of attention and information processing. Nicotine also improved the ability of DAT patients to detect a flickering light in a critical flicker fusion test. These results suggest that nicotine may be acting on cortical mechanisms involved in visual perception and attention, and support the hypothesis that acetylcholine transmission modulates vigilance and discrimination. Nicotine may therefore be of some value in treating deficits in attention and information processing in DAT patients.
*[https://sci-hub.st/10.1192/bjp.154.6.797 PDF Version]
*Citation: Sahakian B, Jones G, Levy R, Gray J, Warburton D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry. 1989 Jun;154:797-800. doi: 10.1192/bjp.154.6.797. PMID: 2597885.
 

='''Antimicrobial Agent'''=
*As a follow-up to these provocative findings, future related studies should examine whether nicotine exerts its anti-microbial effects against a much broader range of indigenous microflora than has been studied so far, along with focusing on the molecular biologic mechanisms and host pathologic changes associated with nicotine-mediated killing of the oral and intestinal microflora.
**Citation: Pavia CS, Plummer MM. Clinical implications of nicotine as an antimicrobial agent and immune modulator. Biomed Pharmacother. 2020 Sep;129:110404. doi: 10.1016/j.biopha.2020.110404. Epub 2020 Jun 27. PMID: 32603888; PMCID: PMC7320263.
***Acknowledgement: This work was partially supported by funds provided by the Department of Biomedical Sciences, NYIT College of Osteopathic Medicine. The authors thank the publisher of the Journal of Medical Microbiology (JMM) for granting us permission to reuse in this paper, without being subject to any copyright infringement, some of the material previously published by one of us (CSP) in the JMM. We also thank Jane Pavia for contributing to the design of the graphical abstract.
 

='''Aphthous ulcers''' (See also: Behcet's disease)=

===2015: [https://pmc.ncbi.nlm.nih.gov/articles/PMC4387635/ Use of pure nicotine for the treatment of aphthous ulcers]===
*The theory that nicotine is known as the protective factor is also supported by three case reports, in which aphthous ulcers were prevented or healed while the patients used nicotine replacement materials.
*To summarize, the use of pure nicotine in therapeutic forms, seems to be a proper alternative to treat aphthous ulcers; however, there has not been any evidence-based case-control study to prove such claim.
**Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

===2014: [https://pubmed.ncbi.nlm.nih.gov/25584320/ Recurrent aphthous ulcers among tobacco users- hospital based study]===
*The tobacco consumers have less frequency of aphthous ulceration compared non users.
**Citation: Mohamed S, Janakiram C. Recurrent aphthous ulcers among tobacco users- hospital based study. J Clin Diagn Res. 2014 Nov;8(11):ZC64-LC66. doi: 10.7860/JCDR/2014/10368.5145. Epub 2014 Nov 20. PMID: 25584320; PMCID: PMC4290331.

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2004: [https://pubmed.ncbi.nlm.nih.gov/15370162/ The relationship between smoking cessation and mouth ulcers]===
*Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.
**Citation: McRobbie H, Hajek P, Gillison F. The relationship between smoking cessation and mouth ulcers. Nicotine Tob Res. 2004 Aug;6(4):655-9. doi: 10.1080/14622200410001734012. PMID: 15370162.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===
*This study shows that a group of RAS patients is significantly less likely to contain smokers than a matched control population, and among smokers the level of cigarette use was significantly lower in RAS patients than the control population. The perceived negative association between RAS and smoking was supported by this epidemiological study.
*[https://sci-hub.st/10.1034/j.1601-0825.2002.01826.x PDF Version]
**Citation: Atkin PA, Xu X, Thornhill MH. Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Dis. 2002 May;8(3):173-6. doi: 10.1034/j.1601-0825.2002.01826.x. PMID: 12108762.

===2000: [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418

===1992: [https://pubmed.ncbi.nlm.nih.gov/1408021/ Smokeless tobacco use prevents aphthous stomatitis]===
*In (contrast to cigarette smoking, however, few components other than nicotine are systemically absorbed by ST users. Thus if the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.
*[https://sci-hub.se/10.1016/0030-4220(92)90296-3 PDF Version]
**Citation: Grady D, Ernster VL, Stillman L, Greenspan J. Smokeless tobacco use prevents aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):463-5. doi: 10.1016/0030-4220(92)90296-3. PMID: 1408021.

===1991 [https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1991.tb121180.x?sid=nlm%3Apubmed Recurrent aphthous ulcers and nicotine]===
*The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers.
*[https://sci-hub.st/10.5694/j.1326-5377.1991.tb121180.x PDF Version]
**Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x
 

='''Arthritis/Skeletal'''=

==Osteoarthritis==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2019 [https://journals.aai.org/jimmunol/article/203/2/485/107400/Nicotine-Attenuates-Osteoarthritis-Pain-and-Matrix Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor]===
*In conclusion, stimulation of α7-nAChRs by nicotine attenuates MIA-induced OA pain and cartilage degradation. This protective effect of nicotine can be associated with the inhibition of MMP-9 overexpression through the PI3K/Akt/NF-κB signaling pathway. Although the use of nicotine is limited by its nonspecific effects, this study provides novel evidence supporting the future development of therapeutic strategies for inflammatory diseases via the cholinergic anti-inflammatory pathway.
**Citation: Teng P, Liu Y, Dai Y, Zhang H, Liu WT, Hu J. Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor. J Immunol. 2019 Jul 15;203(2):485-492. doi: 10.4049/jimmunol.1801513. Epub 2019 May 31. PMID: 31152077.
***This work was supported by grants from the National Natural Science Foundation of China (81373397, 81672218, and 81603092) and the Department of Science, Education, and Health Program of Jiangsu Province (QNRC 2016606 and QNRC 2016604).

==Rheumatoid arthritis (collagen-induced arthritis CIA in mice)==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2016 [https://www.spandidos-publications.com/mmr/14/6/5057 Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration]===
*Animal study
*Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.
**Citation: Li S, Zhou B, Liu B, Zhou Y, Zhang H, Li T, Zuo X. Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration. Mol Med Rep. 2016 Dec;14(6):5057-5064. doi: 10.3892/mmr.2016.5904. Epub 2016 Oct 31. PMID: 27840928; PMCID: PMC5355730.
***Acknowledgement: The present study was supported by a grant from the National Natural Science Foundation of China (grant no. 81571602).

===2014 [https://pubmed.ncbi.nlm.nih.gov/24313917/ Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells]===
*Animal Study
*Nicotine stimulation attenuated signs and severity of arthritis in mice. Activation of nicotine acetylcholine receptors on in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may play a potential role in alleviating arthritis in mice.
*[https://sci-hub.st/10.3109/14397595.2013.862352 PDF Full paper]
**Citation: Yang Y, Yang Y, Yang J, Xie R, Ren Y, Fan H. Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells. Mod Rheumatol. 2014 Sep;24(5):781-7. doi: 10.3109/14397595.2013.862352. Epub 2013 Dec 9. PMID: 24313917.
***Acknowledgement: This work was supported by The Shanghai Committee of Science and Technology Project, China (Grant No. 12GWZX0201,11140902900).

===2014 [https://www.sciencedirect.com/science/article/abs/pii/S0014299914003033 Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine]===
*Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses, may improve the Th1/Th2 imbalance in CIA, and provide a new justification for its application in the clinical treatment of RA.
*[https://sci-hub.st/10.1016/j.ejphar.2014.04.019 PDF Full paper]
**Citation: Wu S, Luo H, Xiao X, Zhang H, Li T, Zuo X. Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol. 2014 Jul 15;735:97-104. doi: 10.1016/j.ejphar.2014.04.019. Epub 2014 Apr 19. PMID: 24755145.
***Acknowledgement: This work was supported by a grant from the National Natural Science Foundation of China, People's Republic of China [81102261] and the Innovative Research Funds for the Central South University, People's Republic of China. [CX2012B088].

===2009 [https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.24177 Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice]===
*Animal Study
*Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction.
**Citation: van Maanen MA, Lebre MC, van der Poll T, LaRosa GJ, Elbaum D, Vervoordeldonk MJ, Tak PP. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 2009 Jan;60(1):114-22. doi: 10.1002/art.24177. PMID: 19116908.

='''Ataxia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

= '''Auditory''' =

===2021 [https://www.nature.com/articles/s41598-021-92588-z Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers]===
*The present study evaluated acute effects of oral nicotine treatment on three auditory tasks in young adult and elderly, healthy, non-smoking individuals. All had normal hearing within the frequency range of the stimuli presented for the three tasks. Compared to pre-treatment performance, nicotine improved frequency discrimination. Compared to placebo, nicotine produced no overall effects on the two frequency related tasks, but significantly improved intensity discrimination, with more improvement obtained for those who had lower baseline performance. The present results support the hypothesis that nicotine enhances auditory processing, but this enhancement is task-dependent.
*[https://www.nature.com/articles/s41598-021-92588-z.pdf PDF Version]
*Citation: Sun, S., Kapolowicz, M.R., Richardson, M. et al. Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers. Sci Rep 11, 13187 (2021). doi: 10.1038/s41598-021-92588-z

===2019 [https://pubmed.ncbi.nlm.nih.gov/31832719/ Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers]===
*Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.
*[https://sci-hub.se/10.1007/s00213-019-05421-x PDF Version]
*Citation: Pham CQ, Kapolowicz MR, Metherate R, Zeng FG. Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers. Psychopharmacology (Berl). 2020 Mar;237(3):833-840. doi: 10.1007/s00213-019-05421-x. Epub 2019 Dec 12. PMID: 31832719; PMCID: PMC7039769.
*Acknowledgements: This research was supported by grants from the National Institutes of Health to FGZ (5R01DC015587), to RM (4R01-DC013200) and a pre-doctoral fellowship to CQP (UL1-TR000153).
*Keywords: Acetylcholinergic systems; Auditory processing; Nicotine; Selective attention; Spectral ripple discrimination; Temporal gap detection; Tone in noise detection.

='''Autism'''=

===2025: [https://link.springer.com/article/10.1007/s12035-025-04894-6 Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism]===
*Animal Study
*Accumulating evidence indicates that nicotinic receptor subtypes are altered in the brains of autistic individuals, and nicotinic acetylcholine receptors (nAChRs) play essential roles in autistic profiles in BTBR T+ Itpr3tf/J mice.
*Biochemical analysis showed that nicotine had significantly decreased the concentration of inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, and GM-CSF in the serum, and reduced the expression levels of intracellular pro-inflammatory cytokines (IL-17 & IFN-γ) on CD4+ and CD8+ T cells in the blood while mecamylamine reversed the effect of IL-17+ CD4+ T cells.
*Nicotine administration up-regulated the expressions of α7, α4, and β2 nAChRs in the prefrontal cortex in BTBR T+ Itpr3tf/J mice.
*The current results indicate that nAChRs play a significant role, at least in part, in ASD and might serve as a crucial target for therapeutic interventions in ASD.
**Citation: AlSharari, S.D., Mahmood, H.M., Alasmari, A.F. et al. Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism. Mol Neurobiol (2025). https://doi.org/10.1007/s12035-025-04894-6
***Acknowledgement: Researchers Supporting Project number (RSPD2025R829), King Saud University, Riyadh, Saudi Arabia. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

===2020: [https://pubmed.ncbi.nlm.nih.gov/32691528/ The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model]===
*Animal Study
*Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people.
*Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism.
*Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model.
*LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.
*[https://sci-hub.st/10.1002/aur.2342 PDF Full paper]
**Citation: Mahmood HM, Aldhalaan HM, Alshammari TK, Alqasem MA, Alshammari MA, Albekairi NA, AlSharari SD. The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model. Autism Res. 2020 Aug;13(8):1311-1334. doi: 10.1002/aur.2342. Epub 2020 Jul 21. PMID: 32691528.
***Acknowledgement: The authors would like to thank the support from the Center for Autism Research (CFAR), King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia.

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
**Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
***Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).

===2016: [https://pmc.ncbi.nlm.nih.gov/articles/PMC5101145/ Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia]===
*Animal Study
*
**Citation:
***Acknowledgement:

===2016: [https://pubmed.ncbi.nlm.nih.gov/27638450/ Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system]===
*Animal Study
*
*[https://sci-hub.st/10.1016/j.neuropharm.2016.09.013 PDF Full paper]
**Citation:
***Acknowledgement:

===2015: [https://pubmed.ncbi.nlm.nih.gov/26337613/ Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system]===
*Animal Study
*
**Citation:
***Acknowledgement:
 

='''Behcet's disease''' (See also: Aphthous ulcers)=
*Post on [https://healthunlocked.com/behcetsuk/posts/138632782/nicotine-and-it%E2%80%99s-effects-on-my-beh%C3%A7et%E2%80%99s-for-the-positive Behçet's UK]. A person started smoking seeking relief from the pain they suffered because of Behcet's disease.

===2010 [https://academic.oup.com/rheumatology/article/49/3/501/1786816 Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series]===
*In this report, we describe five ex-smoker [[Special:MyLanguage/Abbreviations|'''BD''']] patients with active mucocutaneous lesions, not responsive to standard pharmacological treatments and treated with transdermal nicotine patches. Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of all mucocutaneous lesions within 6 months of observation.
**Citation: Giovanni Ciancio, Matteo Colina, Renato La Corte, Andrea Lo Monaco, Francesco De Leonardis, Francesco Trotta, Marcello Govoni, Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series, Rheumatology, Volume 49, Issue 3, March 2010, Pages 501–504, doi: 10.1093/rheumatology/kep401

===2007 [https://www.jidonline.org/article/S0022-202X(15)33112-2/fulltext Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease]===
*"In conclusion, we observed substantial inhibitory effects of CSE and nicotine on IL-8 and to a lesser extent on IL-6 release by human keratinocytes and HMEC-1 endothelial cells. These findings may explain the beneficial effect of smoking in BD, also because IL-8, and to some extent IL-6, are likely to induce pivotal proinflammatory signals in this disease (Lee et al., 1993). Nicotine may cause immunoregulation by affecting chemokine/cytokine production. This study also demonstrates the different behavior of cells in terms of cytokine release when stimulated with BD patients' sera compared to those of healthy individuals. The in vitro evidence of beneficial effects of nicotine in BD is fundamental to our ongoing clinical trial with nicotine transdermal patches in BD. In addition, the detected beneficial effect of biochanin A implicates this compound as a candidate for future developments in aphthae treatment. The development of topical nicotinic cholinergic receptor subtype-specific agonists is likely to exhibit beneficial effects on skin and mucosae without inducing systemic adverse effects."
**Citation: Kalayciyan A, Orawa H, Fimmel S, Perschel FH, González JB, Fitzner RG, Orfanos CE, Zouboulis CC. Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease. J Invest Dermatol. 2007 Jan;127(1):81-9. doi: 10.1038/sj.jid.5700492. Epub 2006 Sep 28. PMID: 17008886.
***Acknowledgement: Dr Kalayciyan was supported by a grant of the Berlin Foundation for Dermatology. The research project was supported by the Deutsches Register Morbus Adamantiades–Behçet e.V.

===2000 [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===
*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)
**Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418
 

='''Brain Injuries, Strokes, Brain Diseases'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/39921606/ The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]===
*Animal Study
*The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke. This finding suggests that targeting the BBB, especially endothelial cells, with nicotine treatment is a promising therapeutic strategy for brain injury after ischemic stroke.
**Citation: Pang Q, Yan X, Chen Z, Yun L, Qian J, Dong Z, Wang M, Deng W, Fu Y, Hai T, Chen Z, Rong X. The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier. Nicotine Tob Res. 2025 Feb 8:ntaf034. doi: 10.1093/ntr/ntaf034. Epub ahead of print. PMID: 39921606.
***Acknowledgement: Paywalled, unable to access

===2024: [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://pubmed.ncbi.nlm.nih.gov/38698493/ Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury]===
*Animal study
*Conclusioin: "Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions."
**Citation: Wang D, Li X, Li W, Duong T, Wang H, Kleschevnikova N, Patel HH, Breen E, Powell S, Wang S, Head BP. Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury. Br J Pharmacol. 2024 Sep;181(17):3082-3097. doi: 10.1111/bph.16395. Epub 2024 May 2. PMID: 38698493.
***Acknowledgement: H. H. P. and B. P. H. hold equity and are non-paid consultants with Eikonoklastes Therapeutics LLC. Funding information: (TRDRP 2020 T31IR1834 to BPH, VA Merit BX003671 and VA RCS BX006318 to BPH, AL210059 to BPH, Craig H. Neilsen Foundation 886964 to SW and BX005229 to HHP).

===2004: [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===
*Several studies have shown that nicotine treatment can attenuate cognitive deficits produced by medial septal lesions, lesions of the nucleus basalis, and traumatic brain injury.
*[https://sci-hub.st/10.1196/annals.1332.019 PDF Version]
**Citation: Pauly JR, Charriez CM, Guseva MV, Scheff SW. Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease. Ann N Y Acad Sci. 2004 Dec;1035:316-34. doi: 10.1196/annals.1332.019. PMID: 15681815.
***Acknowledgements: This work was supported by grants from the National Institutes of Health (NS42196 to J.R.P. and NS39828 to S.W.S.) and the Kentucky Tobacco Research and Development Center. We acknowledge the technical assistance of Melissa Yingling and Khaled Tanwir.

='''Cancer / Cancer Treatments'''=
===2021 [https://www.mdpi.com/1660-3397/19/2/118 α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells]===
*Animal Study
*We tested the effects of nicotine, which is an agonist for all nAChRs with the exception of α9 subtype for which it is antagonist. At concentrations of 0.001–0.1µL/mL (6.1 µM–0.61 mM), nicotine exerted no effect on the proliferative activity of glioma C6 cells and the loss of viability was 1–4% (Figure S2). Analysis by light microscopy showed that nicotine at concentrations of 1 µL/mL (6.1 mM) and higher induced morphological changes like cell rounding up and loss of processes followed by surface detachment (Figure 3). Despite these changes, we investigated the effect of nicotine at a concentration of 1 μL/mL (6.1 mM) on the proliferation and viability of C6 cells. At this nicotine concentration, inhibition of proliferation was observed, which after 72 h led to a decrease in the number of cells by more than two times; the viability was also reduced (Figure S2). However, it should be taken into account that the reason for such a strong decrease in the concentration of cells may be their detachment from the surface and, as a consequence, the cessation of division. We tested acetylcholine at concentrations ranging from 2 µM to 2 mM with incubation times of 24, 48 and 72 h. No effects of acetylcholine were observed.
**Citation: Terpinskaya, T. I., Osipov, A. V., Kryukova, E. V., Kudryavtsev, D. S., Kopylova, N. V., Yanchanka, T. L., Palukoshka, A. F., Gondarenko, E. A., Zhmak, M. N., Tsetlin, V. I., & Utkin, Y. N. (2021). α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Marine Drugs, 19(2), 118. https://doi.org/10.3390/md19020118
***Acknowledgement: This work was supported by the Belarusian Republican Foundation for Fundamental Research, project number M20R-254, and the Russian Foundation for Basic Research, project number 20-54-00033.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S001448272030416X?via%3Dihub Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells]===
*Nicotine inhibits ovarian cancer cell ERK and p38 [[Special:MyLanguage/Abbreviations|'''MAPK''']] signaling.
*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]
**Citation: Sarah J. Harmych, Jay Kumar, Mesa E. Bouni, Deborah N. Chadee, Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells, Experimental Cell Research, Volume 394, Issue 1, 2020, 112167, ISSN 0014-4827, doi: 10.1016/j.yexcr.2020.112167.
***Acknowledgements: This work was supported by the National Institutes of Health [R15 CA199164] and [R15 CA241898] to D.N.C.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

='''Cannabis / THC'''=
===2020 [https://pubmed.ncbi.nlm.nih.gov/32034447/ Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial]===
*The findings provide the first evidence that [[Special:MyLanguage/Abbreviations|NP (Nicotine Patch)]] may be able to attenuate NA (negative affect) - related withdrawal symptoms in individuals with cannabis use disorder who are not heavy users of tobacco or nicotine.
*[https://sci-hub.se/10.1007/s00213-020-05476-1 PDF Version]
*Citation: Gilbert DG, Rabinovich NE, McDaniel JT. Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial. Psychopharmacology (Berl). 2020 May;237(5):1507-1519. doi: 10.1007/s00213-020-05476-1. Epub 2020 Feb 7. PMID: 32034447.
*Acknowledgement: The study was supported by NIH grant R01DA031006 awarded to David Gilbert.
*Keywords: Cannabis; Marijuana; Negative affect; Nicotine; Smoking; THC; Testing effect; Withdrawal symptoms.

= '''Cardiovascular''' =
*See also: Brain Injuries and Strokes

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38529793/ Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects] ===
* This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers.
* PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
* Nicotine patches appear to promote blood vessel formation, without adverse effects.

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2015 [https://www.nature.com/articles/srep15895 Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3] ===

* The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis.
* The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group.
* The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
* Animal study (mice)
* Ge Li-Sha, Zhao Jing-Lin, Chen Guang-Yi, Liu Li, Zhou De-Pu & Li Yue-Chun ''Scientific Reports'' volume 5, Article number: 15895 (2015)

='''Chlamydia Pneumoniae'''=
*Chlamydia pneumoniae is a type of bacteria that can cause respiratory tract infections, such as pneumonia. C. pneumoniae is one cause of community-acquired pneumonia or lung infections developed outside of a healthcare setting. However, not everyone exposed to C. pneumoniae will develop pneumonia. [https://www.cdc.gov/pneumonia/atypical/cpneumoniae/index.html Source: US CDC]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''Cognitive / IQ / Memory'''=
*See also: Sleep - REM

=== 2024: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/ An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence] ===
*Conclusion: Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.
*Citation: Harry J. Green, Olivia K. O’Shea, Jack Cotter, Helen L. Philpott, and Nik Newland. Harm Reduct J. 2024; 21: 78. Published online 2024 Apr 6. doi: 10.1186/s12954-024-00993-0 PMCID: PMC10998423

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnins.2023.1252705/full Editorial: Nicotine and its derivatives in disorders of cognition: a challenging new topic of study] ===

* Front. Neurosci., 18 July 2023 Sec. Neurodegeneration Volume 17 - 2023 | <nowiki>https://doi.org/10.3389/fnins.2023.1252705</nowiki>
* Albert Gjedde, Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
* Nicotine is a compound of considerable interest to neuroscience, in contexts of physiology as well as pathology of brain functions related to neurotransmitter mechanisms. Nicotine is an alkaloid that exists naturally in plants such as tomatoes and potatoes, with the highest levels in the tobacco plant.
* In mammalian brains, nicotine has multiple actions that appear to be accidents of evolution, as no specific relation springs to mind between the functions of nicotine in plants and animals.
* The following discussion expands upon the three topics of biology, therapy, and possible prevention, as related to cognition, in the three reviews and the three original studies included in the collection.
** Conclusion: Questions remain of how nicotine treatment in normal aging should proceed, including length of treatment, dose of nicotine, handling of smokers, effects of AD risk factors, and many others. While data from studies of psychiatric and memory-impaired subjects indicate that nicotine may relieve cognitive symptoms, it is mandatory to test the benefits of nicotine in normal aging in order to fill gaps in the literature and to verify the extent to which nicotine is useful as a pharmacologic agent that prevents pathological aging.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36736944/ Nicotine's effect on cognition, a friend or foe?] ===
* In this review, we first introduce the beneficial effect of nicotine on cognition including attention, short-term memory and long-term memory. We next summarize the beneficial effect of nicotine on cognition under pathological conditions, including Alzheimer's disease, Parkinson's disease, Schizophrenia, Stress-induced Anxiety, Depression, and drug-induced memory impairment.
* We can only access the abstract, but would be interested to read the whole thing if anyone can help?
* Human study
* Qian Wang, Weihong Du, Hao Wang, Panpan Geng, Yanyun Sun, Junfang Zhang, Wei Wang, Xinchun Jin, PMID: 36736944 DOI: 10.1016/j.pnpbp.2023.110723

=== 2021: [https://www.spandidos-publications.com/10.3892/mmr.2021.12037# Molecular insights into the benefits of nicotine on memory and cognition] ===

* Published online on: March 25, 2021 Molecular Medicine Reports <nowiki>https://doi.org/10.3892/mmr.2021.12037</nowiki> Article Number: 398
* Author: Ahmad Alhowail

===2021: [https://www.sciencedirect.com/science/article/abs/pii/S1001841721007804 Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS]===
*Animal study
*Exposure to nicotine mainly altered the secretion of serotonin, kynurenic acid, choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition, and the change are closely related to the dose and duration of exposure.
**Citation: Chen Z, Fu L, Liu X-A, Yang Z, Li W, Li F, Luo Q. Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS. Chin Chem Lett. 2022;33(6):3101–5.
***Acknowledgement: This work was financially supported by the National Natural Science Foundation of China (No. 22076197), the Scientific Instrument Developing Project of the Chinese Academy of Sciences (No. YJKYYQ20200034), Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development (No. XMHT20190204002), Shenzhen Science and Technology Innovation Commission (No. JCYJ20200109115405930), Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020B1515120080).
*Article: [https://medicalxpress.com/news/2021-10-reveal-nicotine-hippocampal-dependent-cognition.html Researchers reveal how nicotine influences hippocampal-dependent cognition] "These results suggested the acute exposure to nicotine was beneficial to protect the neurons, especially cognitive enhancement, and the elevated picolinic acid continually protected neuronal cognitive function after nicotine withdrawal. Furthermore, the dynamic alterations of neurotransmitter metabolism induced by nicotine might be a possible protective mechanism of nicotine on hippocampal dependent cognition."

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0306452220304723?via%3Dihub Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study]===
*Nicotine improves sustained attention and reduces distractor interference, promoting cognitive stability. Nicotine enhances response times without differential impact on task switching or distraction.
*[https://sci-hub.se/10.1016/j.neuroscience.2020.07.029 PDF Version]
*Citation: Stefan Ahrens, Christiane M. Thiel, Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study, Neuroscience, Volume 444, 2020, Pages 43-53, ISSN 0306-4522, doi: 10.1016/j.neuroscience.2020.07.029.
*Acknowledgements: This work was supported by a grant from the German Research Foundation DFG TH766/8-1.
*Key words: nicotine, cholinergic, cognitive control, distraction, task switching, neuroimaging

===2019: [https://www.frontiersin.org/articles/10.3389/fnins.2018.01002/full#B5 Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review]===
*Nicotine lowers learning and memory impairment in some neurological disorders.
*Citation: Majdi, A., Kamari, F., & Gjedde, A. (2019). Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.01002

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
*Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine’s effects.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]
*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.nature.com/articles/npp201715 Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention]===
*Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory–inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.
**Citation: Bueno-Junior, L., Simon, N., Wegener, M. et al. Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Neuropsychopharmacol 42, 1590–1598 (2017). https://doi.org/10.1038/npp.2017.15
***Acknowledgement: This work was supported by São Paulo Research Foundation, Brazil (FAPESP; fellowships 2012/21387-8 and 2012/06123-4) for investigator LSBJ, R01MH084906 (BM), and a pilot fund from the Center for Evaluation of Nicotine in Cigarettes (NWS). The authors declare no conflict of interest.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]

===2012: [https://pubmed.ncbi.nlm.nih.gov/22503574/ The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition]===
*The e-cigarette can reduce desire to smoke and nicotine withdrawal symptoms 20 minutes after use.
*The nicotine content in this respect may be more important for males.
*The first study to demonstrate that the nicotine e-cigarette can improve working memory.
*[https://sci-hub.se/10.1016/j.addbeh.2012.03.004 PDF Version]
*Citation: Dawkins, L., Turner, J., Hasna, S., & Soar, K. (2012). The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition. Addictive Behaviors, 37(8), 970–973. doi:10.1016/j.addbeh.2012.03.004
*Electronic Cigarette Company (TECC) supplied the e-cigarettes and cartridges for this study. TECC had no involvement in the design or conduct of the study.

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated

===2003 [https://www.nature.com/articles/1300202 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects]===
*Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention.
*[https://www.nature.com/articles/1300202.pdf PDF Version]
*Citation: Mumenthaler, M., Yesavage, J., Taylor, J. et al. Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects. Neuropsychopharmacol 28, 1366–1373 (2003). doi: 10.1038/sj.npp.1300202
*Acknowledgements: This research was supported in part by NIMH Grant 40041; NIA Grant AG17824; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC); the Alcohol Beverage Medical Research Foundation; the Swiss Foundation for Alcohol Research; the Swiss National Science Foundation; and the Medical Research Service of the Department of Veterans Affairs.
*Keywords: cholinergic agents, ethanol, cognition, psychomotor performance, psychopharmacology, aerospace medicine

===1996 [https://link.springer.com/article/10.1007/BF02805972 Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers]===
*These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.
*Citation: Foulds, J., Stapleton, J., Swettenham, J. et al. Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacology 127, 31–38 (1996). https://doi.org/10.1007/BF02805972

===1994 [https://link.springer.com/article/10.1007/BF02245346 Smoking and raven IQ]===
*Nicotine has recently been shown to enhance measures of information processing speed including the decision time (DT) component of simple and choice reaction time and the string length measure of evoked potential waveform complexity. Both (DT and string length) have been previously demonstrated to correlate with performance on standard intelligence tests ([[Special:MyLanguage/Abbreviations|'''IQ''']]).
*In this experiment we used the Raven [[Special:MyLanguage/Abbreviations|'''Advanced Progressive Matrices (APM)''']] test. APM scores were significantly higher in the smoking session compared to the non-smoking session, suggesting that nicotine acts to enhance physiological processes underlying performance on intellectual tasks.
*[https://sci-hub.st/https://link.springer.com/article/10.1007/BF02245346 PDF Version]
*Citation: Stough, C., Mangan, G., Bates, T. et al. Smoking and raven IQ. Psychopharmacology 116, 382–384 (1994). doi: 10.1007/BF02245346
*Key words: Intelligence, APM, Nicotine, Smoking Cholinergic system

===1992 [https://pubmed.ncbi.nlm.nih.gov/1579636/ Nicotine as a cognitive enhancer]===
*Nicotine improves attention in a wide variety of tasks in healthy volunteers.
*Nicotine improves immediate and longer term memory in healthy volunteers.
*Nicotine improves attention in patients with probable Alzheimer's Disease.
*While some of the memory effects of nicotine may be due to enhanced attention, others seem to be the result of improved consolidation as shown by post-trial dosing.
*[https://sci-hub.st/10.1016/0278-5846(92)90069-q PDF Version]
*Citation: Warburton DM. Nicotine as a cognitive enhancer. Prog Neuropsychopharmacol Biol Psychiatry. 1992 Mar;16(2):181-91. doi: 10.1016/0278-5846(92)90069-q. PMID: 1579636.
*Keywords: acetylcholine, Alzheimer's Disease, attention, cholinergic, memory, nicotine, scopolamine.
 

='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
*See Also: The Inflamation Section

===2025: [https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00167-8 Long COVID – a critical disruption of cholinergic neurotransmission?]===
*Conclusions: "A review of the literature indicates that a significant disruption of cholinergic neurotransmission might be a central issue for both LC/ME/CFS and PVS. The hypothesis of a viral blockade of nAChRs and the possibility of a competitive reversal of this blockade by LDTN has been corroborated by highly promising results in the broad application of this method to numerous patients. Randomized controlled trials are necessary to determine whether these preliminary results can be substantiated by evidence. However, LDTN application provides many patients with a method that offers a high probability of symptom relief with only minor side effects and represents an affordable therapeutic intervention for the majority of people affected worldwide. Furthermore, dose-finding studies are required to develop individually adapted therapy regimens with regard to dosage and duration of therapy."
*Citation: Leitzke, M., Roach, D.T., Hesse, S. et al. Long COVID – a critical disruption of cholinergic neurotransmission?. Bioelectron Med 11, 5 (2025). https://doi.org/10.1186/s42234-025-00167-8

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===
* States the obvious: the exposure (smoke vs. nicotine and dose need to be characterised correctly).
* Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.
* Salehi Z, Motlagh Ghoochani BFN, Hasani Nourian Y, Jamalkandi SA, Ghanei M. Allergy Asthma Clin Immunol. 2023 Jun 1;19(1):49. doi: 10.1186/s13223-023-00797-0. PMID: 37264452 Review.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36650574/ Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?] ===
* Nicotine COVID/SARS-CoV-2 interaction mystery takes another turn.
* Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh).
* We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.
*In all four of the cases we studied, transcutaneous use of nicotine led to a near immediate improvement in symptoms and rapid restitutio ad integrum. The course of symptom improvement was as distinct as the clinical presentation of post-COVID-19 syndrome in each patient.
*Citation: Leitzke M. Bioelectron Med. 2023 Jan 18;9(1):2. doi: 10.1186/s42234-023-00104-7. PMID: 36650574 Free PMC article.

===2023: [https://www.nature.com/articles/s41598-023-45072-9 Treatment of 95 post-Covid patients with SSRIs]===
*To stick nicotine patches helps PCS (post-COVID syndrome) patients. This may be not only because nicotine is a nicotinic receptor agonist and therefore an opponent of these poisonous metabolites, but nicotine is a strong acetylcholine (ACh) agonist as well.
*Citation: Rus, C.P., de Vries, B.E.K., de Vries, I.E.J. et al. Treatment of 95 post-Covid patients with SSRIs. Sci Rep 13, 18599 (2023). https://doi.org/10.1038/s41598-023-45072-9

===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183099/ Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials]===
* Studies show that the penetration of SARS-CoV-2 into upper respiratory tract, bronchial and pulmonary cells involve transmembrane receptor ACE2, which probably interacts with acetylcholine nicotinic receptors of the α7 subtype. The mechanism of the interactions remains hypothetical.
* Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
* Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.
* Excessive secondary cytokine reaction plays a role in the mortality associated with COVID. One of the hypotheses to explain the effect of nicotine on the occurrence of severe forms of COVID and death is based on the loss of the downregulation of the parasympathetic nervous system, which exerts an inhibitory effect on cytokine storm, especially in the lung and digestive tract. The α 7-type nicotinic receptors are part of this chain of reaction.
* B. Dautzenberg, A. Levi, M. Adler, and R. Gaillardc. Respir Med Res. 2021 Nov; 80: 100844. Published online 2021 Jun 7. doi: 10.1016/j.resmer.2021.100844 PMCID: PMC8183099 PMID: 34153704

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
*Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
*Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.

===2020: [https://www.sciencedirect.com/science/article/pii/S2214750020302924 Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system]===
*Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.
*Citation: Farsalinos K, Niaura R, Le Houezec J, Barbouni A, Tsatsakis A, Kouretas D, Vantarakis A, Poulas K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep. 2020 Apr 30;7:658-663. doi: 10.1016/j.toxrep.2020.04.012. PMID: 32355638; PMCID: PMC7192087.

=== 2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679833/ Mitochondria as a possible target for nicotine action] ===

* See also this twitter thread for detailed information on possible mechanisms. https://x.com/angryhacademic/status/1741968457296490977?s=20
* This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design.
* The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.
* J Bioenerg Biomembr. 2019; 51(4): 259–276. Published online 2019 Jun 13. doi: 10.1007/s10863-019-09800-z PMCID: PMC6679833 PMID: 31197632

='''Digestive Tract / Bowel'''=
===2024: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntae193/7727428 The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis]===
*"Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients."
**Citation: Kastratovic N, Markovic V, Arsenijevic A, Volarevic A, Zdravkovic N, Zdravkovic M, Brankovic M, Gmizic T, Harrell CR, Jakovljevic V, Djonov V, Volarevic V. The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis. Nicotine Tob Res. 2024 Aug 5:ntae193. doi: 10.1093/ntr/ntae193. Epub ahead of print. PMID: 39101540.
***Paywalled, unable to view funding/COI

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S000927971931734X Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model]===
*Animal study
*Conclusion: "Taken together, we demonstrated that nicotine inhibits apoptosis and proliferation by modulating AMPK/mTOR pathway-mediated autophagy and improves colitis severity in the DSS-induced UC mouse model. These findings provide new insights into the mechanism of nicotine treatment on UC autophagy. Further exploration of the mechanism of nicotine in autophagy and targeting factors might be considered a new approach for ulcerative colitis treatment."
*[https://sci-hub.st/10.1016/j.cbi.2020.108943 PDF Full paper]
**Citation: Gao Q, Bi P, Luo D, Guan Y, Zeng W, Xiang H, Mi Q, Yang G, Li X, Yang B. Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model. Chem Biol Interact. 2020 Feb 1;317:108943. doi: 10.1016/j.cbi.2020.108943. Epub 2020 Jan 10. PMID: 31926917.
***Acknowledgement: This work was supported by the Yunnan Key Laboratory of Tobacco Chemistry Project [Grant No. 2017539200340397].

===2018 [https://academic.oup.com/jleukbio/article-abstract/104/5/1013/6935503 Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment]===
*Animal/Cell study
*These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM-1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC.
*[https://sci-hub.st/10.1002/JLB.3A0717-304R PDF Full paper]
**Citation: Maruta K, Watanabe C, Hozumi H, Kurihara C, Furuhashi H, Takajo T, Okada Y, Shirakabe K, Higashiyama M, Komoto S, Tomita K, Nagao S, Ishizuka T, Miura S, Hokari R. Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. J Leukoc Biol. 2018 Nov;104(5):1013-1022. doi: 10.1002/JLB.3A0717-304R. Epub 2018 Jun 14. PMID: 29901817.
***Acknowledgement: This research was supported by grants from the National Defense Medical College, by Grants-in-aid for the Intractable Diseases Project of the Ministry of Health, Labour, and Welfare of Japan, and by Grantsin-aid for Scientific Research from the Japanese Ministry of Education (2646080).

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533410/ Novel Insights on the Effect of Nicotine in a Murine Colitis Model]===
*Animal study
*Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-α.
**Citation: AlSharari SD, Akbarali HI, Abdullah RA, Shahab O, Auttachoat W, Ferreira GA, White KL, Lichtman AH, Cabral GA, Damaj MI. Novel insights on the effect of nicotine in a murine colitis model. J Pharmacol Exp Ther. 2013 Jan;344(1):207-17. doi: 10.1124/jpet.112.198796. Epub 2012 Oct 31. PMID: 23115221; PMCID: PMC3533410.
***Acknowledgement: This work was supported by National Institutes of Health [Grants DA-019377; (to M.I.D.) and DK 046367] (to H.I.A.).

===2012 [https://journals.physiology.org/doi/full/10.1152/ajpgi.00411.2011 Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation]===
*Animal study
*"In summary, in an acute and postinflammatory model of colitis, we demonstrated that nAChRs mediate suppression of hyperexcitability of colonic sensory. The present study also highlights the potential of in vivo treatment with nicotine towards its antinociceptive effects in colonic inflammation."
**Citation: Abdrakhmanova GR, Kang M, Imad Damaj M, Akbarali HI. Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G740-7. doi: 10.1152/ajpgi.00411.2011. Epub 2012 Jan 12. PMID: 22241859; PMCID: PMC3330777."
***Acknowledgement: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-046367 (to H. I. Akbarali).

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2008 [https://www.hindawi.com/journals/grp/2008/237185/ Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study]===
*Smoking has a detrimental effect in [[Special:MyLanguage/Abbreviations|'''Crohn's disease (CD)''']], but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits [[Special:MyLanguage/Abbreviations|'''ulcerative colitis (UC)''']], and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis.
*In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.
*[http://downloads.hindawi.com/journals/grp/2008/237185.pdf PDF Version]
**Citation: J. R. Ingram, J. Rhodes, B. K. Evans, and G. A. O. Thomas, Hindawi Publishing Corporation, Gastroenterology Research and Practice, Volume 2008, Article ID 237185, 6 pages, doi:10.1155/2008/237185
***Acknowledgements: J. R. Ingram was supported by the Gastrointestinal Foundation Trust. SLA Pharma gave financial support to the project. The authors are indebted to Dr. J. T. Green (of Cardiff and Vale Hospitals Trust) who referred patients, and to Professor G. T. Williams (GTW) who performed all histological assessments.

===2004 [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full Transdermal nicotine for induction of remission in ulcerative colitis]===
*Ulcerative colitis is largely a disease of nonsmokers and patients who have quit smoking. Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis.
*[https://sci-hub.st/https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full PDF Version]
**Citation: McGrath, J., McDonald, J. W., & MacDonald, J. K. (2004). Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004722.pub2
***Acknowledgements: Funding for the IBD/FBD Review Group (October 1, 2005 - September 30, 2010) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch; the Canadian Agency for Drugs and Technologies in Health (CADTH); and the CIHR Institutes of Health Services and Policy Research; Musculoskeletal Health and Arthritis; Gender and Health; Human Development, Child and Youth Health; Nutrition, Metabolism and Diabetes; and Infection and Immunity. Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12072594/ Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice]===
*Animal Study
*Conclusions: (1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides.
*[https://sci-hub.st/10.1097/00042737-200206000-00005 PDF of full paper]
**Citation: Eliakim R, Fan QX, Babyatsky MW. Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice. Eur J Gastroenterol Hepatol. 2002 Jun;14(6):607-14. doi: 10.1097/00042737-200206000-00005. PMID: 12072594.

===1999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/ Nicotine treatment for ulcerative colitis]===
*No withdrawal symptoms suggesting nicotine addiction have been reported either after 4–6 weeks of therapy in short-term studies, or after a period of up to 6 months in the only long-term study available
*It can be concluded from these data that transdermal nicotine alone has limited efficacy in active ulcerative colitis and is ineffective as maintenance treatment. On the other hand, if administered in combination with mesalazine, nicotine is superior to placebo in promoting clinical remission of ulcerative colitis of mild to moderate degree, may represent an efficacious alternative to steroids in selected cases and, when effective, seems to exert a longer-lasting therapeutic effect than prednisone.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/pdf/bcp0048-0481.pdf PDF Version]
**Citation: Guslandi M. Nicotine treatment for ulcerative colitis. Br J Clin Pharmacol. 1999 Oct;48(4):481-4. doi: 10.1046/j.1365-2125.1999.00039.x. PMID: 10583016; PMCID: PMC2014383.
***No funding/COI information

===1996 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398677/ The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.]===
*Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial deterrent of UC and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.
*[https://sci-hub.st/10.1136/pgmj.72.854.714 PDF Version]
**Citation: Birtwistle J. The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis. Postgrad Med J. 1996 Dec;72(854):714-8. doi: 10.1136/pgmj.72.854.714. PMID: 9015463; PMCID: PMC2398677.

===1996: [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of ulcerative colitis.
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1994: [https://pubmed.ncbi.nlm.nih.gov/8114833/ Transdermal nicotine for active ulcerative colitis]===
*The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.
**Citation: Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994 Mar 24;330(12):811-5. doi: 10.1056/NEJM199403243301202. PMID: 8114833.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against ulcerative colitis (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Down's Syndrome'''=
===2001: [https://link.springer.com/chapter/10.1007/978-3-7091-6262-0_19 Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome]===
*To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5–31 years) received placebo and a single dose of transdermal nicotine (5mg patch) over 2h in a single-blind, within-subjects repeated measures design.
*Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.
*Citation: Bernert G., Sustrova M., Sovcikova E., Seidl R., Lubec G. (2001) Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. In: Lubec G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_19

===2000 [https://pubmed.ncbi.nlm.nih.gov/11052587/ Effects of transdermal nicotine on cognitive performance in Down's syndrome]===
*We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalizable because of small numbers.
*[https://sci-hub.st/10.1016/S0140-6736(00)02848-8 PDF Version]
*Seidl R, Tiefenthaler M, Hauser E, Lubec G. Effects of transdermal nicotine on cognitive performance in Down's syndrome. Lancet. 2000 Oct 21;356(9239):1409-10. doi: 10.1016/S0140-6736(00)02848-8. PMID: 11052587.
*Acknowledgements: We thank Pharmacia-Upjohn, Uppsala, Sweden, for providing transdermal nicotine patches. This study was supported by the Red Bull Company, Salzburg.
 

='''Dyskinesia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
*In summary, our data show that nicotine treatment decreases haloperidol-induced VCMs [vacuous chewing movements] in an established rat model of tardive dyskinesia. The demonstration that nicotine removal leads to a return of VCMs, whereas nicotine re-exposure reduced haloperidol-induced VCMs, suggests a causal relationship. These data have clinical applications for the treatment of tardive dyskinesias associated with long-term antipsychotic treatment using nicotine.
**Citation: Bordia T, McIntosh JM, Quik M. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. J Pharmacol Exp Ther. 2012 Mar;340(3):612-9. doi: 10.1124/jpet.111.189100. Epub 2011 Dec 5. PMID: 22144565; PMCID: PMC3286320.
***Acknowledgement: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS47162, NS59910]; and the National Institutes of Health National Institute of Mental Health [Grant MH53631]
 

='''Dystonia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.
 

='''Endurance / Exercise / Athletic Performance'''=

===2024 Article: [https://web.archive.org/web/20241002001111/https://www.golfdigest.com/story/tour-pros-little-helper-does-nicotine-create-a-competitive-advantage Tour Pro’s Little Helper: Does nicotine create a competitive advantage?]===
*"In all, we talked to nearly 100 pro golfers to learn more about the popularity and usage patterns of nicotine on the major professional tours. Some told us they turn to tobacco or nicotine products for an energy boost; others say it helps them concentrate or feel relaxed. But for many, it’s just about keeping on."

===2023 [https://www.mdpi.com/1660-4601/20/2/1009 The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study]===
*The lower perception of pain intensity that we reported after the 8 mg nicotine dose application might be an important factor that affects performance. However, we did not report any improvement in physical performance parameters.
**Citation: Bartík P, Šagát P, Pyšná J, Pyšný L, Suchý J, Trubák Z, Petrů D. The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study. Int J Environ Res Public Health. 2023 Jan 5;20(2):1009. doi: 10.3390/ijerph20021009. PMID: 36673765; PMCID: PMC9859273.
***Acknowledgement: The authors would like to acknowledge the support of Prince Sultan University for paying the article processing charges (APC) of this publication. This study was conducted by the SSDRL research group.

===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745004/ Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players]===
*Our HRV and salivary analysis revealed that nicotine could induce endocrine and sympathetic nerve activity in healthy male baseball players who had never smoked. Compared with the placebo group, the nicotine group exhibited enhanced cognitive function (an average decrease in motor reaction time of 11.14%; an average decrease in motor reaction time of 5.72%) and baseball-hitting performance (an average increase of 34.69%), and small effect sizes were observed for these results. However, muscle strength did not increase after nicotine intake.
**Citation: Fang SH, Lu CC, Lin HW, Kuo KC, Sun CY, Chen YY, Chang WD. Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players. Int J Environ Res Public Health. 2022 Jan 4;19(1):515. doi: 10.3390/ijerph19010515. PMID: 35010774; PMCID: PMC8745004.
***Acknowledgement: Study was supported by the Ministry of Science and Technology in Taiwan (No: MOST 107-2410-H-028-002-MY2 and MOST 109-2410-H-028-009-MY3).

===2022 [https://www.tandfonline.com/doi/full/10.1186/s12970-021-00413-9 Nicotine supplementation enhances simulated game performance of archery athletes]===
*In summary, these results indicated that 2-mg nicotine gum supplementation enhanced cognitive function, decreased saliva α-amylase activity and HRV through stimulating the sympathetic adrenergic system. More importantly, the archery scores were significantly increased after nicotine supplementation.
**Citation: Hung BL, Chen LJ, Chen YY, Ou JB, Fang SH. Nicotine supplementation enhances simulated game performance of archery athletes. J Int Soc Sports Nutr. 2021 Feb 18;18(1):16. doi: 10.1186/s12970-021-00413-9. PMID: 33602279; PMCID: PMC7890628.
***Acknowledgement: Funded by the Taiwan Ministry of Science and Technology (MOST104–2628-H-028-001-MY2).

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236038/ A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males]===
*The present study has demonstrated that low-dose (2 mg) nicotine gum increases leg extensor torque, but counter-movement jump and anaerobic capacity during WAnT remained unchanged when compared to a placebo, whilst there were minimal effects of the 4-mg nicotine gum on the performance parameters measured. Together with our previous observation [24], these results indicate that nicotine per se can improve exercise endurance and muscular strength, something that WADA should continue to monitor alongside patterns of (mis)use.
**Citation: Mündel T, Machal M, Cochrane DJ, Barnes MJ. A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males. Sports Med Open. 2017 Dec;3(1):5. doi: 10.1186/s40798-016-0074-8. Epub 2017 Jan 13. PMID: 28092056; PMCID: PMC5236038.
***Acknowledgement: This study was funded in part by a grant from the World Anti-Doping Agency.

===2006 [https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2006.033373 Effect of transdermal nicotine administration on exercise endurance in men]===
*Nicotine improved exercise endurance by 17 ± 7%, and in the absence of any effect on the usual peripheral markers, such as ventilation, heart rate and blood metabolites, we conclude that nicotine prolongs endurance by a central mechanism that may involve nicotinic receptor activation and/or altered activity of dopaminergic pathways.
*[https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2006.033373 PDF Version]
**Citation: Mündel T, Jones DA. Effect of transdermal nicotine administration on exercise endurance in men. Exp Physiol. 2006 Jul;91(4):705-13. doi: 10.1113/expphysiol.2006.033373. Epub 2006 Apr 20. PMID: 16627574.
 

='''Eyes - Ocular - Vision'''=
==Myopia (short-sighted, near-sighted)==
===2024 [https://iovs.arvojournals.org/article.aspx?articleid=2800816 Administration of Nicotine Can Inhibit Myopic Growth in Animal Models]===
*Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia.
**Citation: Thomson K, Karouta C, Ashby R. Administration of Nicotine Can Inhibit Myopic Growth in Animal Models. Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):29. doi: 10.1167/iovs.65.11.29. PMID: 39292451; PMCID: PMC11412605.
***Acknowledgement: Funded by ANU Connect Ventures through a Discovery Translation Fund grant (Project ID: DTF311).
 

='''Hashimoto's disease (Hashimoto thyroiditis)'''=
*[https://www.hopkinsmedicine.org/health/conditions-and-diseases/hashimotos-thyroiditis Hashimoto's Thyroiditis] "is when your thyroid gland becomes irritated or inflamed. Hashimoto thyroiditis is the most common type of this health problem. It may also be called chronic autoimmune thyroiditis. This thyroiditis is an autoimmune disease. It occurs when your body makes antibodies that attack the cells in your thyroid. The thyroid gland becomes overrun with white blood cells and becomes scarred. This makes the gland feel firm and rubbery. The thyroid then can’t make enough of the thyroid hormone."

===2020: [https://www.endocrine-abstracts.org/ea/0070/ea0070oc8.4?_ga=2.114580999.1434360570.1735281186-102848752.1735281184 Cigarette smoking and the risk to develop symptoms of Hashimoto’s thyroiditis]===
*"In patients who had discontinued smoking at the age of 39 years or more, the diagnosis of HT was predominantly made after the discontinuation of smoking."

===2013: [https://onlinelibrary.wiley.com/doi/10.1111/cen.12222 Smoking and thyroid]===
*"Smoking has distinct associations with thyroid function and size in healthy subjects. It has remarkable and contrasting associations with thyroid function in autoimmune thyroid disease (lower risk of Hashimoto's disease and higher risk of Graves’ disease) and with thyroid size in nodular disease (lower risk of thyroid carcinoma and higher risk of nontoxic goitre and multinodularity). The observed associations likely indicate causal relationships in view of consistent associations across studies, the presence of a dose–response relationship and disappearance of the associations after cessation of smoking. Which mechanisms mediate the many effects of smoking remains largely obscure. Probably, they differ between the various effects. The divergent effects of smoking on the expression of autoimmune thyroid disease are intriguing and reminiscent on the contrasting effects of smoking on inflammatory bowel disease: protective against ulcerative colitis (OR 0·41, 0·34–0·48) but risky for Crohn's disease (OR 1·61, 1·27–2·03)."
*[https://sci-hub.st/10.1111/cen.12222 PDF Full paper]
**Citation: Wiersinga, W. M. (2013). Smoking and thyroid. Clinical Endocrinology, 79(2), 145–151. doi:10.1111/cen.12222
***Acknowledgement: None stated

='''HIV (human immunodeficiency virus)'''=

===2025: [https://www.sciencedirect.com/science/article/abs/pii/S0149763425003495 Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential]===
*"Approximately half of people with HIV (PWH) experience neurocognitive impairment (NCI), despite antiretroviral therapies that have turned what was formerly a death sentence to a chronic illness. No targeted treatments exist for HIV-associated NCI, impacting long-term quality of life. Smoking rates in PWH are nearly double those of the general population, and with evidence for pro-cognitive effects of nicotine, this may reflect self-medication. However, clinical studies yield inconsistent findings-some showing benefits, others reporting harm-likely due to variability in nicotine exposure methods, cognitive testing paradigms, withdrawal states, and confounding comorbidities. In contrast, animal studies offer a more controlled framework to isolate the effects of nicotine. Preclinical models suggest that nicotine may mitigate HIV-associated cognitive deficits by acting on α7 nicotinic acetylcholine receptors (nAChRs), leading to reduced neuroinflammation. These findings highlight the therapeutic potential of targeting nAChRs, though mechanisms remain incompletely understood..."
**Citation: Jha NA, Ayoub SM, Brody AL, Young JW. Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential. Neurosci Biobehav Rev. 2025 Aug 23;177:106348. doi: 10.1016/j.neubiorev.2025.106348. Epub ahead of print. PMID: 40854454.
***Acknowledgement: This work was supported by the National Institutes of Health [grant numbers: R01MH134175 (JWY), R01MH128869 (JWY), R01DA051295 (JWY)]...

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.
**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2
***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

='''Huntington’s Disease'''=

===2005: [https://pubmed.ncbi.nlm.nih.gov/16140176/ Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats]===
*These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.
*In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.
*[https://sci-hub.se/10.1016/j.brainresbull.2005.06.024 PDF Version]
**Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.
 

='''Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis''' (See Also: Allergies/Hayfever/Histamines)=
*[https://www.nhlbi.nih.gov/health/hypersensitivity-pneumonitis Hypersensitivity pneumonitis] is a rare immune system disorder that affects the lungs. This disease is also called bird or pigeon fancier’s lung, farmer’s lung, hot tub lung, cheese worker's lung, Bagassosis, mushroom worker's lung, malt worker's lung, or humidifier lung.
*[https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity pneumonitis] (HP) classified as an interstitial lung disease is characterized by a complex immunological reaction of the lung parenchyma in response to repetitive inhalation of a sensitized allergen.

===2023: [https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity Pneumonitis]===
*Cigarette smoking seems to protect from developing clinically significant HP likely due to nicotine inhibiting macrophage activation and lymphocyte proliferation.
*However, smokers who develop HP have been shown to have a more severe course and higher mortality.
**Citation: Chandra D, Cherian SV. Hypersensitivity Pneumonitis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499918/

===2007: [https://academic.oup.com/qjmed/article-abstract/100/4/233/2258683?redirectedFrom=fulltext Extrinsic allergic alveolitis: incidence and mortality in the general population]===
*We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at ∼0.9 cases per 100 000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39–0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05–4.33).
**Citation: M. Solaymani-Dodaran, J. West, C. Smith, R. Hubbard, Extrinsic allergic alveolitis: incidence and mortality in the general population, QJM: An International Journal of Medicine, Volume 100, Issue 4, April 2007, Pages 233–237, https://doi.org/10.1093/qjmed/hcm008

===2002: [https://www.atsjournals.org/doi/10.1164/rccm.200210-1154OC Inhibitory Effect of Nicotine on Experimental Hypersensitivity Pneumonitis In Vivo and In Vitro]===
*Animal study
*Results of this study show that nicotine reduces the alveolar inflammatory response to S. rectivirgula antigen and affects some AM (stimulated with LPS or S. rectivirgula) functions in vitro. This influence could be, at least in part, responsible for the protection that smokers have against development of HP. Because nicotine is effective in the treatment of ulcerative colitis, it could also be of interest in the treatment of HP and other pulmonary inflammatory diseases.
**Citation: Blanchet MR, Israël-Assayag E, Cormier Y. Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med. 2004 Apr 15;169(8):903-9. doi: 10.1164/rccm.200210-1154OC. Epub 2003 Dec 30. PMID: 14701707.

===1992: [https://pubmed.ncbi.nlm.nih.gov/1344064/ Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum]===
*It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.
**Citation: Arima K, Ando M, Ito K, Sakata T, Yamaguchi T, Araki S, Futatsuka M. Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum. Arch Environ Health. 1992 Jul-Aug;47(4):274-8. doi: 10.1080/00039896.1992.9938361. PMID: 1344064.

===1987: [https://pubmed.ncbi.nlm.nih.gov/3499342/ Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking]===
*Farmer's lung was only slightly more common among atopic than among non-atopic subjects and twice as common among non-smokers as among smokers.
**Citation: Terho EO, Husman K, Vohlonen I. Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking. Eur J Respir Dis Suppl. 1987;152:19-28. PMID: 3499342.

===1977: [https://pmc.ncbi.nlm.nih.gov/articles/PMC470791/ Extrinsic allergic alveolitis: a disease commoner in non-smokers.]===
*In the literature of extrinsic allergic alveolitis non-smokers predominate in those papers in which smoking habits are recorded (Hapke et al., 1968; Schlueter et al., 1969; Schofield et al., 1976). Studies of the prevalence of precipitating antibodies against Micropolyspora faeni in farmers have shown that they are detected significantly more often in non-smokers than in smokers (Morgan et al., 1975).
**Citation: Warren CP. Extrinsic allergic alveolitis: a disease commoner in non-smokers. Thorax. 1977 Oct;32(5):567-9. doi: 10.1136/thx.32.5.567. PMID: 594937; PMCID: PMC470791.
 

='''Hypothyroidism'''=

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===
*Animal Study
*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).
* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]
**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.
***Acknowledgement: None stated
 

='''Inflammation'''=

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871277/ Effect of Nicotine on Immune System Function]===
*Despite the completely destructive and harmful effects of cigarette smoke, nicotine via stimulation of the α7 receptor can promote the anti-inflammatory benefits on the immune system. However, these effects depend on the concentration, and administration methods are different and sometimes contradictory. It can be used successfully to treat or inhibit autoimmune diseases. Although the exact mechanism of this treatment is unknown, it appears to involve inhibiting downstream intracellular pathways that lead to the secretion of pre-inflammatory cytokines.
**Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.
**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.
***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
*Analysis of several studies - some animal.
*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
**Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889
***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
**Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483
***Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
*Case study of one individual
*Nicotine, an α7-nACh receptor agonist, may boost the cholinergic anti-inflammatory pathway and hinder the uncontrolled overproduction of pro-inflammatory cytokines triggered by the SARS-CoV-2 virus, which is understood to be the main pathway to poor outcomes and death in severe COVID-19.
*In the absence of any effective treatment for COVID-19, further research as to whether nicotine replacement offers protection against severe SAR-CoV-2 infection in smokers is clearly essential. If the mechanisms through which nicotine may interact with the virus remain speculative, the effects of route of administration, duration, dosing and frequency of use of nicotine on any such interaction are unknown. Should NRT be found to be of help in the management of COVID-19, it would be yet another strong reason to persuade smokers to switch to NRT and ultimately quit smoking.
**Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.
***Acknowledgement: All authors have declared that no financial support was received from any organization for the submitted work.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
**Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.
***Acknowledgement: This work was supported by University of Castilla-La Mancha Research Programme 2020-GRIN-28705.

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila and Chlamydia pneumonia infection...
**Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2011 [https://pubmed.ncbi.nlm.nih.gov/21691078/ Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells]===
*In summary, we showed that nicotine could suppress TNF-α expression mainly through activation of the α7 nAChR subunit, which inhibited the MyD88/IκBα/NFκB signaling pathway in HBE16 airway epithelial cells. These findings may provide new information on the potential pharmacological effects of nicotine and nAChR in the treatment of respiratory inflammatory diseases. Further research on nicotine and nAChRs may provide more evidence for the treatment of inflammatory diseases and the development of related drugs.
*[https://www.karger.com/Article/Pdf/329982 PDF Version]
**Citation: Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982
***Acknowledgement: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===
*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
**Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
***Acknowledgement: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.

===2008 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693390/ Neuronal Nicotinic Alpha7 Receptors Modulate Inflammatory Cytokine Production in the Skin Following Ultraviolet Radiation]===
*Animal study
*Cytokine responses to UV in mice administered chronic oral nicotine, a nAChR agonist, were reduced... These results demonstrate that nAChRα7 can participate in modulating a local pro-inflammatory response in the absence of parasympathetic innervation.
**Citation: Osborne-Hereford AV, Rogers SW, Gahring LC. Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation. J Neuroimmunol. 2008 Jan;193(1-2):130-9. doi: 10.1016/j.jneuroim.2007.10.029. PMID: 18077004; PMCID: PMC2693390.
***Acknowledgement: These studies were funded by NIH grants DA015148 and DA018930 (LCG), PO1 HL72903 (LCG, SWR) and the Browning Foundation of Utah.

===2006 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809735/ Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7]===
*Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-α, prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-1α and MIP-1α, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet’s disease and Crohn’s disease. In addition, the nicotinic acetylcholine receptor-α7 (α7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the α7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes.
*These suppressive effects of nicotine were caused at the transcriptional level and were mediated through α7nAChR. Nicotine suppressed the phosphorylation of I-κB, and then inhibited the transcriptional activity of nuclear factor-κB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.
*This supports the therapeutic use of nicotine in some inflammatory diseases; the NF-κB activation pathway is one of the most critical molecular targets of nicotine therapy.
**Citation: Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. 2006 Oct;146(1):116-23. doi: 10.1111/j.1365-2249.2006.03169.x. PMID: 16968406; PMCID: PMC1809735.
 

='''Legionella Pneumophila (Legionnaires' disease)'''=

===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
 

='''ME/CFS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome'''=
*See Also: COVID (Long COVID)
 

='''Mental Health'''=
*See subcategories below
 
=='''Mental Health - Anxiety'''==
===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated
 

=='''Mental Health - Behavior Issues'''==
*See Also: ADD/ADHD above

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0028390819305003?via%3Dihub Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies]===
*Human and Animal Studies
*Clinical trials and case series report anti-aggressive effects of nicotine. Here we argue that the [[Special:MyLanguage/Abbreviations|'''nAChR''']] system, the molecular basis for the global public health problem of tobacco smoking, may also be a key target for modulation of aggressive behaviors. Future research should aim to clarify which forms of aggression are most strongly affected by nAChR modulation, identify the nAChR subtypes, circuits, and neurobiological mechanisms of nicotine action, and determine whether more selective nAChR-active agents can replicate or improve the serenic effects of nicotine, especially with chronic dosing. Given the prevalence of aggressive behaviors across neuropsychiatric disorders affecting the very young to the very old, these studies have the potential to have a significant impact on public health.
*[https://sci-hub.st/https://doi.org/10.1016/j.neuropharm.2019.107929 PDF Version]
*Citation: Alan S. Lewis, Marina R. Picciotto, Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies, Neuropharmacology, Volume 167, 2020, 107929, ISSN 0028-3908, doi: 10.1016/j.neuropharm.2019.107929.
*Acknowledgements: This work was supported by National Institutes of Health grants MH116339 (A.S.L.), MH077681 and DA14241 (M.R.P.).

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
*Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.
*Acknowledgements: This work was supported by Autism Speaks grant #9699 (ASL), National Institutes of Health grants R01DA14241 and R01MH077681 (MRP), R25MH071584, T32MH019961, and T32MH14276 (ASL), and the Child Study Center Associates and the AACAP Pilot Award for General Psychiatry Residents (GIvS).
 

=='''Mental Health - Depression'''==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15950 The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study]===
*In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.
*Citation: Yebo Yu, Fan Yang, Mingqi Fu, Farooq Ahmed, Muhammad Shahid, Jing Guo, Relationship Between Work-Family Conflict and Depressive Symptoms Among Male Firefighters in China, Journal of Occupational & Environmental Medicine, 10.1097/JOM.0000000000002759, 65, 4, (337-343), (2022).

===2021 [https://www.sciencedirect.com/science/article/abs/pii/S0376871621005676 Adolescent depression symptoms and e-cigarette progression]===
*Depression symptoms predicted more rapid e-cigarette progression in adolescents.
*E-cigarette use was not associated with an escalation in depression symptoms.
*E-cigarette use was not related to the development of depression symptoms over time.
*Must pay to view PDF
*Citation: Afaf F. Moustafa, Shannon Testa, Daniel Rodriguez, Stephen Pianin, Janet Audrain-McGovern, Adolescent depression symptoms and e-cigarette progression, Drug and Alcohol Dependence, Volume 228, 2021, 109072, ISSN 0376-8716, doi.org/10.1016/j.drugalcdep.2021.109072.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2000 [https://www.sciencedirect.com/science/article/abs/pii/S0091305700002057 The Effects of Nicotine on Neural Pathways Implicated in Depression: A Factor in Nicotine Addiction?]===
*It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine.
*[https://sci-hub.st/10.1016/S0091-3057(00)00205-7 PDF Version]
*Citation: Balfour, D. J. ., & Ridley, D. L. (2000). The Effects of Nicotine on Neural Pathways Implicated in Depression. Pharmacology Biochemistry and Behavior, 66(1), 79–85. doi:10.1016/s0091-3057(00)00205-7

===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0149763417301793 Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression]===
*Nicotine improves cognitive performance in clinical and preclinical studies.
*Nicotine may also benefit depressive symptoms and depressive behavior.
*Cognitive and mood benefits may be mediated by nicotinic effect on neural networks.
*Nicotine’s effects on networks may reverse network changes seen in depression.
*Improvement to mood and cognition may particularly benefit older depressed adults.
*Both preclinical and clinical studies support that nicotine and other nAChR agonists can improve depressive behavior, mood, and cognitive performance. nAChR agonists also demonstrate neuropharmacologic effects that oppose the intrinsic network alterations reported in MDD. Through modulation of intrinsic functional networks, nAChR agonists may reduce depressive symptoms, enhance emotional regulation ability, and improve cognitive deficits common in LLD. For these reasons, we propose nAChR agonists as a potential novel treatment for the mood and cognitive symptoms of LLD.
*[https://sci-hub.st/10.1016/j.neubiorev.2017.08.018 PDF Version]
*Citation: Gandelman, J. A., Newhouse, P., & Taylor, W. D. (2018). Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression. Neuroscience & Biobehavioral Reviews, 84, 289–298. doi:10.1016/j.neubiorev.2017.08.0
*Acknowledgement: Supported by NIH grants K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences.

===2018 [https://pubmed.ncbi.nlm.nih.gov/29795403/ Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder]===
*In [[Special:MyLanguage/Abbreviations|'''MDD''']], acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD.
*[https://sci-hub.st/10.1038/s41386-018-0069-x PDF Version]
*Citation: Janes AC, Zegel M, Ohashi K, Betts J, Molokotos E, Olson D, Moran L, Pizzagalli DA. Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. Neuropsychopharmacology. 2018 Nov;43(12):2445-2451. doi: 10.1038/s41386-018-0069-x. Epub 2018 Apr 19. PMID: 29795403; PMCID: PMC6180119.
*Acknoledgements: This project was supported by the National Institute on Drug Abuse grants K10 DA029645 and K02 DA042987 (ACJ). DAP was partially supported by National Institute of Mental Health grant R37 MH068376. Over the past 3 years, DAP has received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Pfizer and Posit Science, for activities unrelated to the current research.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/ Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Non-Smokers with Late-Life Depression]===
*[[Special:MyLanguage/Abbreviations|Late '''Life Depression (LLD)''']] is characterized by poor antidepressant response and cognitive dysfunction. Late life depression has no currently approved treatment that improves both its mood and cognitive symptoms.
*We observed robust response (86.7%) and remission rates (53.3%). There was a significant decrease in MADRS (Montgomery-Asberg Depression Rating scale) over the study, with improvement seen as early as three weeks. We also observed improvement in apathy and rumination. We did not observe improvement on the CPT (Conners Continuous Performance Test), but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/pdf/nihms965043.pdf PDF Version]
*Citation: Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137. PMID: 30192444; PMCID: PMC6129985.
*Acknowledgements: This research was supported by NIH grant K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. The sponsor provided funding for the study but did not influence the design or conduct of the study.

===2006 [https://pubmed.ncbi.nlm.nih.gov/16977477/ Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial]===
*These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
*[https://sci-hub.st/10.1007/s00213-006-0516-y PDF Version]
*Citation: McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2006 Nov;189(1):125-33. doi: 10.1007/s00213-006-0516-y. Epub 2006 Sep 15. PMID: 16977477.
*Acknowledgement: This research was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Dr. Rose is an inventor named on several nicotine patch patents and receives royalties from sales of certain nicotine patches.

===2002 [https://pubmed.ncbi.nlm.nih.gov/11995405/ Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients]===
*Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration.
*Citation: Salin-Pascual RJ. Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Rev Invest Clin. 2002 Jan-Feb;54(1):36-40. PMID: 11995405.

===1999 [https://link.springer.com/article/10.1007/s002130050879 Antidepressant effects of nicotine in an animal model of depression]===
*Animal Study
*Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals.
*The data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the [[Special:MyLanguage/Abbreviations|'''FSL''']] rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
*[https://sci-hub.st/https://doi.org/10.1007/s002130050879 PDF Version]
*Citation: Tizabi, Y., Overstreet, D., Rezvani, A. et al. Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142, 193–199 (1999). https://doi.org/10.1007/s002130050879
*Acknowledgements This work was supported in part by the Department of Pharmacology, Howard University, VAMC and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
*Keywords: Key words Nicotine · Nicotinic receptor · FSL and FRL rats · Animal model of depression

===1998 [https://pubmed.ncbi.nlm.nih.gov/9592048/ A novel effect of nicotine on mood and sleep in major depression]===
*Transdermal nicotine patches increased REM sleep in normal volunteers and depressed patients during 4 days of continuous administration. In addition, a significant improvement of mood was observed in depressed patients. Nicotinic mechanisms may be involved in depression. These findings suggest that nicotine receptor activation may be important in major depression and shows for the first time that nicotine patches may be useful in the treatment of depression.
*[https://sci-hub.st/10.1097/00001756-199801050-00012 PDF Version]
*Salín-Pascual RJ, Drucker-Colín R. A novel effect of nicotine on mood and sleep in major depression. Neuroreport. 1998 Jan 5;9(1):57-60. doi: 10.1097/00001756-199801050-00012. PMID: 9592048.
*ACKNOWLEDGEMENT: This work has been supported by the following grants: DGAPA-UNAM IN -200895 to R.J.S-P.

===1996 [https://pubmed.ncbi.nlm.nih.gov/9746444/ Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression]===
*A high frequency of cigarette smoking has been reported among individuals with major depression.
*Results of the visual analog scale and [[Special:MyLanguage/Abbreviations|'''HAM-D''']] showed a significant improvement in depression after the second day of nicotine patches.
*Citation: Salín-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL, Delgado-Parra V. Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry. 1996 Sep;57(9):387-9. PMID: 9746444.

===1996 [https://psycnet.apa.org/record/1996-00468-019 Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.]===
*Depressed smokers relapsed significantly earlier than the nondepressed. Nicotine gum was significantly more effective than placebo gum among all smokers. The benefits of nicotine gum were particularly apparent among the depressed. Only 12.5% of depressed smokers quit successfully with placebo gum for 3 months, whereas 29.5% quit with nicotine gum. Depressed smokers reported more stress, less coping resources, more physical and psychological symptoms, and more frequent smoking in the presence of negative affect than did the nondepressed.
*[https://sci-hub.st/10.1037/0022-006X.64.4.791 PDF Version]
**Citation: Kinnunen, T., Doherty, K., Militello, F. S., & Garvey, A. J. (1996). Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement. Journal of Consulting and Clinical Psychology, 64(4), 791–798. https://doi.org/10.1037/0022-006X.64.4.791

===1995 [https://pubmed.ncbi.nlm.nih.gov/8619011/ Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients]===
*The main finding of the present study was that nicotine patches induced an increase in REM sleep time in depressed patients without any other changes in sleep variables
*[https://sci-hub.st/10.1007/BF02246496 PDF Version]
*Citation: Salín-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colín R. Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology (Berl). 1995 Oct;121(4):476-9. doi: 10.1007/BF02246496. PMID: 8619011.
*Acknowledgement: This work has been supported in part by FIIRESIN, Fideicomiso-UNAM (to RD-C) and DGAPA-UNAM1N203393 (to RJS-P).

===1993 [https://jamanetwork.com/journals/jamapsychiatry/article-abstract/496026 Nicotine Dependence and Major Depression]===
*There is, then, no evidence in these data that the occurrence of MDD in persons with a prior history of nicotine dependence might have been caused directly by recent persistent smoking.
*[https://sci-hub.st/10.1001/archpsyc.1993.01820130033006 PDF Version]
*Citation: Breslau N, Kilbey MM, Andreski P. Nicotine Dependence and Major Depression: New Evidence From a Prospective Investigation. Arch Gen Psychiatry. 1993;50(1):31–35. doi:10.1001/archpsyc.1993.01820130033006

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement (mood normalization) (other issues and diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
*Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

=='''Mental Health - Mental Illness'''==

===2022 [https://academic.oup.com/ntr/article-abstract/24/9/1405/6562456 E-Cigarette Provision to Promote Switching in Cigarette Smokers With Serious Mental Illness—A Randomized Trial]===
*This was the first prospective study to compare e-cigarette provision with assessments only to evaluate the appeal and impact of e-cigarettes on smoking behavior, carbon monoxide exposure, and nicotine dependence among smokers with Severe Mental Illness (SMI) who had tried but were unable to quit and were not currently interested in cessation treatment. The finding that e-cigarette provision led to significant reductions in smoking and carbon monoxide without increasing nicotine dependence has implications for reducing harm not only among the millions of smokers with SMI who struggle to quit, but also for other vulnerable smokers who cannot achieve cessation.
 

=='''Mental Health - OCD (Obsessive Compulsive Disorder)'''==
===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/ Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review]===
*Nicotine may ameliorate OC symptoms in severe, treatment-refractory [[Special:MyLanguage/Abbreviations|'''OCD''']] patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/pdf/12991_2020_Article_309.pdf PDF Version]
*Citation: Piacentino D, Maraone A, Roselli V, Berardelli I, Biondi M, Kotzalidis GD, Pasquini M. Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review. Ann Gen Psychiatry. 2020 Sep 30;19:57. doi: 10.1186/s12991-020-00309-z. PMID: 33014119; PMCID: PMC7528475.
 

=='''Mental Health - PTSD (Post Traumatic Stress Disorder)'''==
===2012 [https://www.hindawi.com/journals/aps/2012/265724/ Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study]===
*Smokers with PTSD report greater NA (Negative Affects) immediately prior to smoking and greater decreases in NA following smoking, and these findings are consistent with the observed patterns of brain activation in the current study. Thus, our findings provide a neurobiological basis that helps explain why individuals with PTSD are at greater risk of smoking and also experience greater difficulty quitting. The present study is not without its limitations. Our sample size was small and was predominately represented by female smokers.
*[https://downloads.hindawi.com/journals/aps/2012/265724.pdf PDF Version]
*Citation: Froeliger, B., Crowell Beckham, J., Feldman Dennis, M., Victoria Kozink, R., & Joseph McClernon, F. (2012). Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study. Advances in Pharmacological Sciences, 2012, 1–6. doi:10.1155/2012/265724
*Acknowledgement: Department of Veterans Affairs or the National Institutes of Health.
 

=='''Mental Health - Schizophrenia'''==
===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fpsyt.2022.804055/full Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence]===
*Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
*[https://twitter.com/hbwardMD/status/1487037135299518474 Twitter thread about this study]
**Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055
***Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0149763420305042?via%3Dihub The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review]===
*Cognitive and early sensory alterations are core features of [https://en.wikipedia.org/wiki/Schizophrenia '''schizophrenia''']. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.
*[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 PDF Version]
**Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.

=== 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===
*Animal Study
*“Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
*Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
**Citation: Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)

===2017: [https://pubmed.ncbi.nlm.nih.gov/28441884/ Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging]===
*This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.
**Citation: Smucny J, Tregellas JR. Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging. J Psychopharmacol. 2017 Jul;31(7):801-811. doi: 10.1177/0269881117705071. Epub 2017 Apr 26. PMID: 28441884; PMCID: PMC5963521.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Citation: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===
*The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.
*[https://sci-hub.st/10.1016/j.mehy.2009.02.017 PDF Version]
**Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

===2007: [https://pmc.ncbi.nlm.nih.gov/articles/PMC2702723/ Nicotinic Interactions with Antipsychotic Drugs, Models of Schizophrenia and Impacts on Cognitive Function]===
*Human and Animal study
*Nicotinic receptor systems in the brain are important for a variety of aspects of cognitive function impaired in schizophrenia and aggravated by antipsychotic drugs. Nicotine and selective nicotinic α7 and α4β2 agonists can significantly improve learning, memory and attention. Nicotine and nicotine agonists can reduce some of the cognitive impairments caused by some antipsychotic drugs as well as reduce cognitive impairments seen in the NMDA glutamate blockade animal model of schizophrenia.
**Citation: Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007 Oct 15;74(8):1182-91. doi: 10.1016/j.bcp.2007.07.019. Epub 2007 Jul 20. PMID: 17714691; PMCID: PMC2702723.
***Acknowledgement: Research presented was supported by a grant from the National Institute of Mental Health grant MH64494.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
**Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.
 

='''Movement Disorders (not diagnosis specific)'''=
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/ Role for the nicotinic cholinergic system in movement disorders; therapeutic implications]===
*Animal Study
*Several [[Special:MyLanguage/Abbreviations|'''nAChR''']] subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/pdf/nihms600497.pdf PDF Version]
*Citation: Quik M, Zhang D, Perez XA, Bordia T. Role for the nicotinic cholinergic system in movement disorders; therapeutic implications. Pharmacol Ther. 2014 Oct;144(1):50-9. doi: 10.1016/j.pharmthera.2014.05.004. Epub 2014 May 14. PMID: 24836728; PMCID: PMC4149916.
*Acknowledgements: This work was supported by grants NS59910 and NS 65851 from the National Institutes of Health.
 

='''Multiple Sclerosis - Humans / Experimental Autoimmune Encephalomyelitis (EAE) - Animals'''=

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Special:MyLanguage/Abbreviations|'''EAE''']] mice via multiple [[Special:MyLanguage/Abbreviations|'''nAChRs''']], including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/pdf/1501613.pdf PDF Version]
**Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

===2015 [https://pubmed.ncbi.nlm.nih.gov/25813705/ Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis]===
*Amimal study
*We found that reduction of ependymal cell proliferation correlated with inflammation in the same area, which was relieved by the administration of nicotine. Further, increased numbers of oligodendrocytes (OLs) were observed after nicotine treatment. These findings give a new insight into the mechanism of how nicotine functions to attenuate EAE.
*[https://sci-hub.st/10.1016/j.neuroscience.2015.03.031 PDF Full Study]
**Citation: Gao Z, Nissen JC, Legakis L, Tsirka SE. Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis. Neuroscience. 2015 Jun 25;297:11-21. doi: 10.1016/j.neuroscience.2015.03.031. Epub 2015 Mar 23. PMID: 25813705; PMCID: PMC4428965.
***Acknowledgement: The work was supported by NMSS PP1815, NIH R01NS42168, NIH IRACDA K12GM102778.

===2015 [https://pubmed.ncbi.nlm.nih.gov/26209886/ Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients]===
*The data obtained highlight the role of α7 receptor subtype in the modulation of anti-inflammatory cytokines also in MS. Moreover the ability of nicotine to up-regulate the expression of α7 receptor subtype in RR-MS patients, indicates that nicotinic receptor stimulation may contribute to down-modulate the inflammation occurred in MS by a positive feedback control of its expression.
*[https://sci-hub.st/10.1016/j.intimp.2015.06.034 PDF Full paper]
**Citation: Reale M, Di Bari M, Di Nicola M, D'Angelo C, De Angelis F, Velluto L, Tata AM. Nicotinic receptor activation negatively modulates pro-inflammatory cytokine production in multiple sclerosis patients. Int Immunopharmacol. 2015 Nov;29(1):152-7. doi: 10.1016/j.intimp.2015.06.034. Epub 2015 Jul 23. PMID: 26209886.
***Acknowledgement: This work was supported by FISM – Fondazione Italiana Sclerosi Multipla – Cod. 2013/R/25. MDB was supported by fellowship on FISM project 2013/R/25.

===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/ The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components]===
*Animal Study
*Our results show that nicotine reduces the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an [[Special:MyLanguage/Abbreviations|'''EAE/MS''']] therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176721/pdf/pone.0107979.pdf PDF Version]
**Citation: Gao Z, Nissen JC, Ji K, Tsirka SE. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One. 2014 Sep 24;9(9):e107979. doi: 10.1371/journal.pone.0107979. PMID: 25250777; PMCID: PMC4176721.
***Acknowledgements: This work was supported by National Multiple Sclerosis Society awards CA1044A1 and PP181, National Aeronautics and Space Administration NNA14AB04A and National Institutes of Health R01NS42168 (ST), and National Institutes of Health K12GM102778 to JN.

===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===
*Animal Study
*Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in [[Special:MyLanguage/Abbreviations|'''EAE''']] as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for [[Special:MyLanguage/Abbreviations|MS]] therapy.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/pdf/icns_10_4_20.pdf PDF Version]
**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.
***Acknowledgement: No funding was provided for the preparation of this article.
 

='''Narcolepsy'''=

===2021: [https://www.authorea.com/doi/full/10.22541/au.162126605.51833119 The therapeutic use of medical nicotine in narcolepsy]===
*PDF: [https://www.researchgate.net/profile/Carolina-Diamandis/publication/351648895_The_therapeutic_use_of_medical_nicotine_in_narcolepsy/links/60aa9cb945851522bc10a4c1/The-therapeutic-use-of-medical-nicotine-in-narcolepsy.pdf The therapeutic use of nicotine in narcolepsy]

===2012: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3311418/ Narcolepsy with Cataplexy Masked by the Use of Nicotine]===
*

===2010: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2823281/ A Novel Approach to Treating Morning Sleep Inertia in Narcolepsy]===
*

='''Nicotine Used With Other Substances'''=

===2021 [https://pubmed.ncbi.nlm.nih.gov/34119664/ Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats]===
*Animal Study
*The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA. (Note: AKA ecstasy)
*Citation: Kowsari G, Mehrabi S, Soleimani Asl S, Pourhamzeh M, Mousavizadeh K, Mehdizadeh M. Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats. J Chem Neuroanat. 2021 Jun 10;116:101986. doi: 10.1016/j.jchemneu.2021.101986. Epub ahead of print. PMID: 34119664.

='''Oral / Jaw'''=
===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===
*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
*Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).
*Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, [https://en.wikipedia.org/wiki/Edema oedema], and [https://en.wikipedia.org/wiki/Trismus trismus] in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
*Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
*Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444372/ Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program]===
*The results of this study confirm that chewing the tested nicotine replacement gum as recommended in a ‘real world’ active smoking cessation program produces a statistically significant change in the parameter of whitening as measured by change from baseline versus the negative control (Microtab) following 6 weeks in a smoking cessation programme. The Vita® Shade Guide (the secondary outcome measure) supported the trend of stain improvement. These results support the efficacy of the tested nicotine replacement gum in stain reduction, in arresting the progression of tooth stain and in shade lightening.
*Acknowledgement: The study was fully funded by McNeil AB who is the manufacturer of the test and control products. It was designed by McNeil AB in consultation with HW and DOM. The study was run, participants recruited, smoking cessation intervention administered and data collected by the team of research staff at the Oral Health Services Research Centre at University College Cork under the leadership of HW with consultant input from DOM. RK carried out the clinical examinations but was blinded to intervention allocation. The data were analysed by McNeil AB with input from HW and DOM. The study was externally monitored by MDS Pharma Services, UK and conducted to ICH GCP standards. The data were interpreted by HW, DOM and RK. The manuscript was drafted by HW with editorial comment from the other authors. HW decided to submit the manuscript for publication.
*Citation: Whelton H, Kingston R, O'Mullane D, Nilsson F. Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program. BMC Oral Health. 2012 Jun 13;12:13. doi: 10.1186/1472-6831-12-13. PMID: 22695211; PMCID: PMC3444372.
 

='''Pain / Analgesic'''=
===2024: [https://pubmed.ncbi.nlm.nih.gov/39719676/ Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial]===
*Postoperative pain scores at rest and on movement were lower in the nicotine group than in the placebo group at 6 hours, 12 hours, and 24 hours after surgery (P<0.05). Postoperative morphine consumption was lower in the nicotine group than in the placebo group (9.92 ± 4.0 vs. 15.9 ± 5.0 mg, respectively; P=0.0002).
**Citation: Maheshwari A, Gupta M, Garg B, Singh AK, Khanna P. Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial. J Neurosurg Anesthesiol. 2024 Dec 25. doi: 10.1097/ANA.0000000000001022. Epub ahead of print. PMID: 39719676.
***Acknowledgement: Paywalled, can not access

===2023: [https://pubmed.ncbi.nlm.nih.gov/37132069/ Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study]===
*Perioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.
**Citation: Zhu C, Bi Y, Wei K, Tao K, Hu L, Lu Z. Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study. Addiction. 2023 Aug;118(8):1579-1585. doi: 10.1111/add.16224. Epub 2023 May 19. PMID: 37132069.
***Acknowledgement: Shanghai Municipal Science and Technology Commission. Grant Number: 17411960400

===2023: [https://www.mdpi.com/1424-8247/16/12/1665 The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis]===
*Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
**Citation: Luo Y, Yang Y, Schneider C, Balle T. The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis. Pharmaceuticals. 2023; 16(12):1665. https://doi.org/10.3390/ph16121665
***Acknowledgement: This work was funded by the Australian Research Council LP160100560.

===2023 [https://www.sciencedirect.com/science/article/abs/pii/S0014299923000298?via%3Dihub Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron]===
*Animal Study
*Nicotine-induced antinociception was inhibited by intrathecal pre-treatment with yohimbine, an α2 adrenergic receptor antagonist. These results indicated that nicotine may suppress BCAO-induced mechanical hypersensitivity through the activation of the descending pain control system via orexin neurons.
**Citation: Nakamoto, K., Matsuura, W., & Tokuyama, S. (2023). Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron. European journal of pharmacology, 175518. Advance online publication. https://doi.org/10.1016/j.ejphar.2023.175518
***Acknowledgement: This work was supported by the Smoking Research Foundation (FP01807092).

===2023: [https://pubmed.ncbi.nlm.nih.gov/36947193/ Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials]===
*Perioperative use of NP significantly improved postoperative pain, even when opioids were administered or prescribed. Nevertheless, the clinical relevance should be interpreted with caution, owing to the effect sizes of the summary measures and methodological issues. The analgesic potential of NP as an adjuvant therapy to regulate pain and acute inflammation may offer certain clinical advantages, thus warranting further investigation.
**Citation: da Silva Barbirato D, de Melo Vasconcelos AF, Dantas de Moraes SL, Pellizzer EP, do Egito Vasconcelos BC. Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials. Eur J Clin Pharmacol. 2023 May;79(5):589-607. doi: 10.1007/s00228-023-03475-7. Epub 2023 Mar 22. PMID: 36947193.
***Acknowledgement: Paywalled, can't access

===2020 [https://pubmed.ncbi.nlm.nih.gov/32381373/ Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial]===
*The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
*This study establishes a new prevention and treatment modality regarding pain, oedema, and trismus in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
*[https://sci-hub.se/10.1016/j.ijom.2019.08.013 PDF Version]
**Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
***Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/ Acute Analgesic Effects of Nicotine and Tobacco in Humans: A Meta-Analysis]===
*Pain and tobacco smoking are both highly prevalent and comorbid conditions, current smoking has been associated with more severe chronic pain and physical impairment, and acute nicotine-induced analgesia could make smoking more rewarding and harder to give up.
*Moderation analyses further revealed that acute analgesic effects may be achieved regardless of nicotine delivery method, current smoking status, pain induction modality, study design, or control condition, and that such effects may be more robust among men than women.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912401/pdf/nihms-774195.pdf PDF Version]
**Citation: Ditre JW, Heckman BW, Zale EL, Kosiba JD, Maisto SA. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain. 2016;157(7):1373-1381. doi:10.1097/j.pain.0000000000000572 (viewed Oct 5, 2021)
***Acknowledgement: This research was supported by NIH Grant Nos. R21DA034285 and R21DA038204 awarded to Joseph W. Ditre, NIH Grant Nos. F31DA033058 and T32DA007288 awarded to Bryan W. Heckman, NIH Grant No. F31DA039628 awarded to Emily L. Zale, and NIH Grant No. 2K05 AA16928 awarded to Stephen A. Maisto.

===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
*Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
*Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]
**Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
***Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.

===2011 [https://journals.lww.com/ejanaesthesiology/Fulltext/2011/08000/Randomised_trial_of_intranasal_nicotine_and.7.aspx Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women]===
*Intraoperative use of intranasal nicotine has a sustained opioid-sparing effect in non-smoking women undergoing gynaecological procedures and is associated with a higher frequency of nausea.
*[https://sci-hub.st/10.1097/EJA.0b013e328344d998 PDF Version]
*Citation: Jankowski, Christopher J.; Weingarten, Toby N.; Martin, David P.; Whalen, Francis X.; Gebhart, John B.; Liedl, Lavonne M.; Danielson, David R.; Nadeau, Ashley M.; Schroeder, Darrell R.; Warner, David O.; Sprung, Juraj Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women, European Journal of Anaesthesiology (EJA): August 2011 - Volume 28 - Issue 8 - p 585-591 doi: 10.1097/EJA.0b013e328344d998
*Acknowledgements: The present work was supported solely by the Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

===2008 [https://journals.lww.com/anesthesia-analgesia/Fulltext/2008/09000/Transdermal_Nicotine_for_Analgesia_After_Radical.48.aspx Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy]===
*The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in postoperative opioid consumption in nonsmoking men undergoing [[Special:MyLanguage/Abbreviations|'''RRP''']] in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
*[https://sci-hub.se/10.1213/ane.0b013e31816f2616# PDF Version]
*Citation: Habib, Ashraf S., MBBCh, MSc, FRCA*; White, William D., MPH*; El Gasim, Magdi A., MD*; Saleh, Gamal, MD*; Polascik, Thomas J., MD†; Moul, Judd W., MD†; Gan, Tong J., MB, FRCA* Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy, Anesthesia & Analgesia: September 2008 - Volume 107 - Issue 3 - p 999-1004 doi: 10.1213/ane.0b013e31816f2616

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12131122/ Isoflurane hyperalgesia is modulated by nicotinic inhibition]===
*Animal study
*Female mice had significant [https://en.wikipedia.org/wiki/Hyperalgesia hyperalgesia] from [https://en.wikipedia.org/wiki/Isoflurane isoflurane]. Nicotine administration prevented isoflurane-induced hyperalgesia without altering the antinociception produced by higher isoflurane concentrations.
**Citation: Flood P, Sonner JM, Gong D, Coates KM. Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology. 2002 Jul;97(1):192-8. doi: 10.1097/00000542-200207000-00027. PMID: 12131122.
***Acknowledgement: 1P01GM47818/GM/NIGMS NIH HHS/United States, K08GM00695/GM/NIGMS NIH HHS/United States
 

='''Parkinson Disease'''=

===2025: [https://pubmed.ncbi.nlm.nih.gov/40465192/ Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease]===
*"In conclusion, these findings suggest potential therapeutic mechanisms of the identified constituents in PD and may provide a basis for future preclinical and clinical studies to further explore their neuroprotective effects."
**Citation: Tusar MTT, Munna MMR, Ahmed MH, Rahman MM, Fatema K, Islam KM, Ali MS. Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulation Guided Discovery of Anethole, Carvacrol, Carnosol, Nicotine, and Paeonol as Potential Therapeutics for Parkinson's Disease. Cell Biochem Biophys. 2025 Jun 4. doi: 10.1007/s12013-025-01791-6. Epub ahead of print. PMID: 40465192.
***The authors declare no competing interests. (No funding information provided on the version viewed at the link above.)

===2024 [https://www.sciencedirect.com/science/article/abs/pii/S0967586824003849 The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial]===
*The results of our study indicated that nicotine consumption in an isocaloric diet, while preventing a decrease in anthropometric indices, leads to improvements in motor indices and a reduction in alpha-synuclein levels. Additional and larger controlled trials are required to validate these findings.
**Citation: Lorvand Amiri H, Hassan Javanbakht M, Mohammad Baghbanian S, Parsaeian M. The effect of a nicotine-rich diet with/without redistribution of dietary protein on motor indices in patients with Parkinson's disease: A randomized clinical trial. J Clin Neurosci. 2024 Sep 30;129:110845. doi: 10.1016/j.jocn.2024.110845. Epub ahead of print. PMID: 39353253.
***Acknowledgement: This work was supported by the Tehran University of Medical Sciences. (Project No. 53161).

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38430248/ Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease] ===
*Animal study (worms with humanised neurons)
*This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction.
*At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS.
*We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.
*''Note: highly technical brain biochemistry, appears to be important however (ed.)'' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586504/ Paper on the UPS and it's purpose] for info.
**Citation: Ullah I, Uddin S, Zhao L, Wang X, Li H. Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease. Exp Brain Res. 2024 Apr;242(4):971-986. doi: 10.1007/s00221-023-06765-9. Epub 2024 Mar 2. PMID: 38430248.
***Acknowledgement: This study was supported by the Special International Cooperation Project of the Ministry of Science and Technology (2012DFA30480); National Natural Science Foundation of China (No. 81403145); Natural Science Foundation of Gansu Province (No. 20JR10RA602); Fundamental Research Funds for the Central Universities of China (lzujbky—2017-206, lzujbky-2018-136); Science and Technology Cooperation Program of Gansu Academy of Sciences (grant number 2019HZ-02); Program of Lanzhou Science and Technology Foundation (Grant number 2010-1-154). Major science and technology project of Gansu province (23ZDFA013), Natural Science Foundation of Gansu province (20JR10RA602).

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

=== 2023: [https://www.frontiersin.org/articles/10.3389/fnagi.2023.1223310/full Changes in smoking, alcohol consumption, and the risk of Parkinson’s disease] ===
*A total of 3,931,741 patients were included.
*Compared to the sustained non-smokers, sustained light smokers, sustained moderate smokers, and sustained heavy smokers had a lower risk of PD.
*Compared to those who sustained non-drinking, sustained light drinkers, sustained moderate drinkers, and sustained heavy drinkers showed decreased risk of PD.
*Among non-drinkers, those who started drinking to a light level were at decreased risk of PD. Among non-smoking and non-drinking participants, those who initiated smoking only, drinking only, and both smoking and drinking showed decreased risk of PD.
*Smoking is associated with decreased risk of PD with a dose–response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.
**Citation: Jung SY, Chun S, Cho EB, Han K, Yoo J, Yeo Y, Yoo JE, Jeong SM, Min JH, Shin DW. Changes in smoking, alcohol consumption, and the risk of Parkinson's disease. Front Aging Neurosci. 2023 Sep 13;15:1223310. doi: 10.3389/fnagi.2023.1223310. PMID: 37771519; PMCID: PMC10525683.
***Acknowledgement: J-HM received a grant from the National Research Foundation of Korea and SMC Research and Development Grant. J-HM has lectured, consulted, and received Honoria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Sanofi Genzyme, Teva-Handok, UCB, Samsung Bioepis, Mitsubishi Tanabe Pharma, and Roche.

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36817162/ Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.] ===
*Animal Study
*Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo.
*In summary, Nic pretreatment ameliorates MPTP-induced dyskinesia and anxiety-like behavior in mice with PD. Nic was found to alleviate neuroapoptosis by improving nigrostriatal dopaminergic damage, reducing the accumulation of pathological p-α-syn, and inhibiting microglia activation and pro-inflammatory factor expression in the substantia nigra and striatal regions of mice brain under MPTP stimulation. These neuroprotective effects of Nic may be achieved by modulating the JNK and ERK signaling pathways in the nigrostriatal system, which was further confirmed by the pretreatment of 5-MOP to decline the brain metabolic activity of Nic.
**Citation: Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. PMID: 36817162; PMCID: PMC9932206.
***Acknowledgement: This study received funding from the National Science Foundation of China (Grant No. 32072344, 82101506, 32272455), the Scientific and Technological Project of Henan Province of China (Grant No. 182102310157) and the Scientific and Technological Project of China Tobacco Jiangsu Industrial Co., Ltd. (No. H202002). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Authors JX, RJ, and ZG were employed by China Tobacco Jiangsu Industrial Co., Ltd.

===2023: [https://jamanetwork.com/journals/jamaneurology/article-abstract/2805037 Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune]===
*“Parkinson disease risk was substantially lower among Black veterans and EVER-SMOKERS (OR 0.49, 95% CI: 0.40-0.61).
**Citation: Goldman SM, Weaver FM, Stroupe KT, Cao L, Gonzalez B, Colletta K, Brown EG, Tanner CM. Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune. JAMA Neurol. 2023 Jul 1;80(7):673-681. doi: 10.1001/jamaneurol.2023.1168. PMID: 37184848; PMCID: PMC10186205.
***Acknowledgement: This research was supported by clinical science research and development merit award I01 CX002040-01 from the US Department of Veterans Affairs. Support for Veterans Administration (VA)/Centers for Medicare & Medicaid Services data was from the US Department of Veterans Affairs, VA Health Services Research and Development Service, and project numbers SDR 02-237 and 98-004 from the VA Information Resource Center. Dr Weaver reported receiving grants from the Edward Hines, Jr VA Hospital during the conduct of the study and outside the submitted work. Dr Brown reported receiving grants from the Michael J. Fox Foundation and the National Institute on Aging and personal fees from Gateway Consulting, LLC, outside the submitted work. Dr Tanner reported receiving personal fees from Lundbeck Pharma, CNS Ratings, Adamas, Cadent, and Evidera; serving on advisory boards for Kyowa Kirin, Acorda, Australia Parkinson’s Mission; serving on a clinical trial steering committee for Jazz Pharmaceuticals/Cavion; and receiving grants from the National Institutes of Health, Biogen Idec, Parkinson Foundation, Michael J. Fox Foundation, Department of Defense Parkinson’s Research Program, Roche, Genentech, BioElectron, and Gateway Institute for Brain Research, LLC, outside the submitted work. No other disclosures were reported.

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602090/ Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-induced Toxicities in Cell Culture]===
*Preprint, not peer-reviewed.
*In summary, our results not only support neuroprotective effects of nicotine and butyrate in countering Fe and Mn toxicities but indicate a synergistic protection by combination of the two. Moreover, distinct mechanisms of action for each metal, i.e., nicotinic receptor for nicotine and FA3R for butyrate are indicated. Further exploitation of mechanisms of action of butyrate and nicotine may provide novel targets for metal toxicities and/or amelioration of neurodegenerative diseases.
**Citation: Tizabi Y, Getachew B, Aschner M. Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases. Res Sq [Preprint]. 2023 Oct 5:rs.3.rs-3389904. doi: 10.21203/rs.3.rs-3389904/v1. Update in: Neurotox Res. 2023 Dec 14;42(1):3. doi: 10.1007/s12640-023-00682-z. PMID: 37886507; PMCID: PMC10602090.
***Acknowledgement: Supported in part by: NIH/NIAAA R03 AA022479 and NIH/NIGMS (2 SO6 GM08016‐39) (YT), and NIEHS R01ES10563 and R01ES07331 (MA).

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36857384/ Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment.] ===
*Insect study
*We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.
**Citation: Carvajal-Oliveros A, Dominguez-Baleón C, Sánchez-Díaz I, Zambrano-Tipan D, Hernández-Vargas R, Campusano JM, Narváez-Padilla V, Reynaud E. Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment. PLoS One. 2023 Mar 1;18(3):e0282348. doi: 10.1371/journal.pone.0282348. PMID: 36857384; PMCID: PMC9977059.
***Acknowledgement: This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 255478 and by Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (DGAPA-PAPIIT) grant number IN206517) ER was the recipient of the grants. AC received fellowships (446128) from CONACYT, PAEP-UNAM and Alianza del Pacífico- AGCID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

===2021 [https://www.nature.com/articles/s41598-021-88910-4 Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels]===
*Insect study
*In conclusion our data show that the PD model by expression of Sph-1 in dopaminergic neurons provides a good opportunity to study the early prodromal stages of PD, while also the late onset symptoms such as neurodegeneration and motor impairment in aged animals. On the other hand, working on this animal model has allowed us to advance on the therapeutic effects of nicotine treatment over several PD-linked features. The protective effect of nicotine appears to be specific for the genotype predisposed to develop a parkinsonian phenotype and provide a hint on the idea that nicotine treatment even in later stages of the disease could be beneficial to patients. Our findings provide new ideas that contribute to a better understanding on the mechanisms underlying the positive effects of nicotine in PD.
**Citation: Carvajal-Oliveros, A., Domínguez-Baleón, C., Zárate, R.V. et al. Nicotine suppresses Parkinson’s disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Sci Rep 11, 9579 (2021). https://doi.org/10.1038/s41598-021-88910-4
***Acknowledgement: This work was supported by the CONACyT (Grant Number 255478) and by DGAPA-PAPIIT (Grant Number IN206517).

=== 2020: [https://n.neurology.org/content/94/20/e2132 Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors] ===
*In contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.
**Citation: Mappin-Kasirer B, Pan H, Lewington S, Kizza J, Gray R, Clarke R, Peto R. Tobacco smoking and the risk of Parkinson disease: A 65-year follow-up of 30,000 male British doctors. Neurology. 2020 May 19;94(20):e2132-e2138. doi: 10.1212/WNL.0000000000009437. Epub 2020 May 5. PMID: 32371450; PMCID: PMC7526668.

===2020 [https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqaa186/5876214?redirectedFrom=fulltext Dietary nicotine intake and risk of Parkinson disease: a prospective study]===
*At 26 year follow-up, women with greater dietary nicotine intake had a lower risk of [[Special:MyLanguage/Abbreviations|'''Parkinson Disease (PD)''']] than those with lower intake. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea.
*[https://sci-hub.st/10.1093/ajcn/nqaa186 PDF Version]
**Citation: Chaoran Ma, Samantha Molsberry, Yanping Li, Michael Schwarzschild, Alberto Ascherio, Xiang Gao, Dietary nicotine intake and risk of Parkinson disease: a prospective study, The American Journal of Clinical Nutrition, Volume 112, Issue 4, October 2020, Pages 1080–1087, doi: 10.1093/ajcn/nqaa186
***Acknowledgements: Supported by National Institute of Neurological Disorders and Stroke at the NIH grant 1R03NS093245-01A1 (to XG). The Nurses’ Health Study is supported by the NIH through grant UM1 CA186107. The Health Professionals Follow-up Study cohort is supported by the NIH through grant U01 CA167552.

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2018 [https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0625-y Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6]===
*Animal study
*The reduced prevalence of Parkinson’s disease in tobacco users is a fascinating phenomenon that is not understood. This study suggests a mechanistic explanation for how tobacco users are protected from Parkinson’s and how the tobacco component nicotine confers neuroprotection; more specifically, nicotine suppresses SIRT6 which confers resistance to neuron and cell death. Few effective treatments exist that prevent neuron death for those suffering from Parkinson’s and other neurodegenerative disorders. The identification of SIRT6 as potentially pathogenic and as a therapeutic target for suppression opens a novel line of research for the treatment of neurodegeneration.
**Citation: Nicholatos, J.W., Francisco, A.B., Bender, C.A. et al. Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6. acta neuropathol commun 6, 120 (2018). https://doi.org/10.1186/s40478-018-0625-y
***Acknowledgement: S.L. and J.W.N. were in part supported by a grant from American Federation for Aging Research (AFAR, grant # 2015–030). S.L. received seed grant funding from the Cornell University Center for Vertebrate Genomics. J.W.N. was supported by a Glenn/AFAR Scholarship for Research in the Biology of Aging.

===2017 [https://academic.oup.com/ije/article/46/3/872/2656164 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Non-smoking men who used snus had a 60% lower risk of Parkinson’s disease compared with never snus users.
**Citation: Yang F, Pedersen NL, Ye W, Liu Z, Norberg M, Forsgren L, Trolle Lagerros Y, Bellocco R, Alfredsson L, Knutsson A, Jansson JH, Wennberg P, Galanti MR, Lager ACJ, Araghi M, Lundberg M, Magnusson C, Wirdefeldt K. Moist smokeless tobacco (Snus) use and risk of Parkinson's disease. Int J Epidemiol. 2017 Jun 1;46(3):872-880. doi: 10.1093/ije/dyw294. PMID: 27940486.
***Acknowledgement: This work was supported by the Swedish Research Council (grant number 521-2013-2488 to N.L.P.) and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (Y.T.L.).

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
**Author/Acknowledgements: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/ Nicotinic receptors as CNS targets for Parkinson’s disease]===
*Human and animal references
*Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/pdf/nihms32016.pdf PDF Version]
**Citation: Quik M, Bordia T, O'Leary K. Nicotinic receptors as CNS targets for Parkinson's disease. Biochem Pharmacol. 2007 Oct 15;74(8):1224-34. doi: 10.1016/j.bcp.2007.06.015. Epub 2007 Jun 17. PMID: 17631864; PMCID: PMC2046219.
***Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*Nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Parkinson's Disease''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against '''Parkinson's Disease''' (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Pemphigus Vulgaris'''=

===2001: [https://pubmed.ncbi.nlm.nih.gov/11737449/ Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire]===
*The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked.
*The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system.
**Citation: Brenner S, Tur E, Shapiro J, Ruocco V, D'Avino M, Ruocco E, Tsankov N, Vassileva S, Drenovska K, Brezoev P, Barnadas MA, Gonzalez MJ, Anhalt G, Nousari H, Ramos-e-Silva M, Pinto KT, Miranda MF. Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire. Int J Dermatol. 2001 Sep;40(9):562-9. doi: 10.1046/j.1365-4362.2001.01266.x. Erratum in: Int J Dermatol. 2003 Sep;42(9):760. Silva MR [corrected to Ramos-e-Silva M]. PMID: 11737449.

===2000: [https://jamanetwork.com/journals/jamadermatology/fullarticle/189739 A Case of Pemphigus Vulgaris Improved by Cigarette Smoking]===
*The patient reported an inverse relationship between smoking and pemphigus flares. He observed a worsening of the pemphigus when he stopped smoking. Nicotine patches were prescribed, but he began smoking cigarettes again instead. On average, he smokes 15 cigarettes per day. One week after he began smoking again, his pemphigus rapidly started to clear.
**Citation: Mehta JN, Martin AG. A case of pemphigus vulgaris improved by cigarette smoking. Arch Dermatol. 2000 Jan;136(1):15-7. doi: 10.1001/archderm.136.1.15. PMID: 10632179.
 

='''Pregnancy'''=
==Preeclampsia==

===2024: [https://www.sciencedirect.com/science/article/abs/pii/S0303720724003022 Nicotine increases hepatocyte transthyretin turnover: a possible mechanism for the protective effect of smoking on preeclampsia?]===
*Nicotine exposure increases hepatocyte synthesis, secretion and uptake of transthyretin as well as cell uptake of soluble endoglin. Nicotine may protect against preeclampsia by increasing serum TTR which can bind soluble endoglin and remove it from the circulation. Further research is required to better understand the role of transthyretin and nicotine in mitigating preeclampsia.
**Citation: Young M, McLeod DSA, Richard K. Nicotine increases hepatocyte transthyretin turnover: A possible mechanism for the protective effect of smoking on preeclampsia? Mol Cell Endocrinol. 2025 Feb 1;597:112446. doi: 10.1016/j.mce.2024.112446. Epub 2024 Dec 24. PMID: 39725350.
***Acknowledgement: This study was funded by the Science Education and Research Committee, Pathology Queensland.
 

='''Psoriasis'''=

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===
*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]
**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.
 

='''Pyoderma Gangrenosum'''=

===2004 [https://pubmed.ncbi.nlm.nih.gov/15204166/ Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream]===
*Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.
*[https://scihubtw.tw/10.1080/09546630310019364 PDF Version]
**Citations:Patel GK, Rhodes JR, Evans B, Holt PJ. Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream. J Dermatolog Treat. 2004 Apr;15(2):122-5. doi: 10.1080/09546630310019364. PMID: 15204166.

===1998 [https://jamanetwork.com/journals/jamadermatology/fullarticle/189304?fbclid=IwAR33gpEktRMf2Q0v5Btl9C5E8gmXw-ZP8_gDFt6sebxUBpXE_WfVt-o-mSw Nicotine for Pyoderma Gangrenosum]===
*Herein we describe a patient with pyoderma gangrenosum who responded twice to topical nicotine within 4 weeks and 3 months, respectively, without any adverse effects.
*[https://scholar.google.com/scholar_url?url=https://jamanetwork.com/journals/jamadermatology/articlepdf/189304/dce8005.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=Z2aqX4SnOc2rywTPj5aYDw&scisig=AAGBfm1pz6ffl3a23G__I3APgBLpY6Cofw PDF Version]
**Citation: Wolf R, Ruocco V. Nicotine for Pyoderma Gangrenosum. Arch Dermatol. 1998;134(9):1071–1072. doi:10.1001/archderm.134.9.1071

===1995 [https://pubmed.ncbi.nlm.nih.gov/8537562/ Successful treatment of pyoderma gangrenosum with nicotine chewing gum]===
*We used nicotine chewing gum for the treatment of pyoderma gangrenosum with remarkable results. We strongly suggest that nicotine chewing gum may not only be beneficial in treating pyoderma gangrenosum but may also be useful in treating other skin disorders with prominent neutrophilic infiltrations such as Behcet's disease, Sweet disease, allergic vasculitis, and recurrent oral aphthae, the last of which is known to respond to smoking.
*[https://sci-hub.st/10.1111/j.1346-8138.1995.tb03904.x PDF Version]
**Citation: Kanekura T, Kanzaki T. Successful treatment of pyoderma gangrenosum with nicotine chewing gum. J Dermatol. 1995 Sep;22(9):704-5. doi: 10.1111/j.1346-8138.1995.tb03904.x. PMID: 8537562.
 

='''Rett syndrome'''=

===2016: [https://www.nature.com/articles/cr201648 Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus]===
*Animal Study
*In addition, application of PNU282987 or nicotine rescued impaired social interaction and anxiolytic behaviors in Chat-Mecp2−/y mice.
*Nicotine appears to be the primary agent in cigarettes that can target all nAChRs, including α7 nAChRs. Application of nicotine also rescued the behavioral phenotypes of Chat-Mecp2−/y mice. Long-term delivery of nicotine in the hippocampus also improved social memory in WT mice...Of particular importance, intracerebral infusion of PNU282987 or nicotine rescued the behavioral defects in Chat-Mecp2−/y mice. These findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.
**Citation: Zhang Y, Cao SX, Sun P, He HY, Yang CH, Chen XJ, Shen CJ, Wang XD, Chen Z, Berg DK, Duan S, Li XM. Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus. Cell Res. 2016 Jun;26(6):728-42. doi: 10.1038/cr.2016.48. Epub 2016 Apr 22. PMID: 27103432; PMCID: PMC4897179.
***Acknowledgement: This work was supported by the National Natural Science Foundation of China for Distinguished Young Scientists (81225007), Key Project of the National Natural Science Foundation of China (31430034), Major Research Plan of the National Natural Science Foundation of China (91432306), Funds for Creative Research Groups of China (81221003), Program for Changjiang Scholars and Innovative Research Team in University, and Fundamental Research Funds for the Central Universities. This work was also sponsored by the Zhejiang Province Program for Cultivation of High-level Health Talents.
 

='''Sarcoidosis'''=

===2021 [https://journal.chestnet.org/article/S0012-3692(21)01282-4/fulltext Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis]===
===2021 [https://journal.chestnet.org/article/S0012-3692(21)00962-4/fulltext A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis]===
*Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC.
**Citation: A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis, Crouser, Elliott D. et al. CHEST, Volume 160, Issue 4, 1340 - 1349

===2013 [https://journal.chestnet.org/article/S0012-3692(13)60095-1/fulltext Nicotine Treatment Improves Toll-Like Receptor 2 and Toll-Like Receptor 9 Responsiveness in Active Pulmonary Sarcoidosis]===
*The immune phenotype of patients with symptomatic [[wikipedia:Sarcoidosis|'''sarcoidosis''']] treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
*[https://www.researchgate.net/profile/Mark_Julian/publication/230645268_Nicotine_Treatment_Improves_TLR2_and_TLR9_Responsiveness_in_Active_Pulmonary_Sarcoidosis/links/556ca4af08aeab77722318be/Nicotine-Treatment-Improves-TLR2-and-TLR9-Responsiveness-in-Active-Pulmonary-Sarcoidosis.pdf PDF Version]
**Citation: Mark W. Julian, MS; Guohong Shao, MD; Larry S. Schlesinger, MD; Qin Huang, MD; David G. Cosmar, BA; Nitin Y. Bhatt, MD; Daniel A. Culver, MD, FCCP; Robert P. Baughman, MD, FCCP; Karen L. Wood, MD, FCCP; and Elliott D. Crouser, MD - ORIGINAL RESEARCH DIFFUSE LUNG DISEASE| VOLUME 143, ISSUE 2, P461-470, FEBRUARY 01, 2013, DOI 10.1378/chest.12-0383
***Acknowledgements: This work was supported by the American Thoracic Society and the Foundation for Sarcoidosis Research. © 2013 American College of Chest Physicians

===1988:[https://thorax.bmj.com/content/43/7/516.abstract Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.]===
*These finding support the possibility that smokers, particularly those with a prominent accumulation of alveolar macrophages in the lower respiratory tract, may be less likely to develop sarcoidosis.
**Citation: Valeyre D, Soler P, Clerici C, et alSmoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.Thorax 1988;43:516-524.
 

='''Seizures / Epilepsy'''=
*See also:
**Video: News 5: [https://www.youtube.com/watch?v=Ztvf45coKZk Nicotine Stops Seizures]

===2024 [https://www.neurology.org/doi/10.1212/WNL.0000000000209790/ Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch]===
*"Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep."
*"Our case highlights that there may be mechanisms by which nicotine assists with seizure cessation in specific populations of individuals with SHE."
**Citation: Nam S, Von Stein EL, Meador KJ, Levy RJ, Gallentine W, Li Y. Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch. Neurology. 2024 Oct 8;103(7):e209790. doi: 10.1212/WNL.0000000000209790. Epub 2024 Sep 9. PMID: 39250747; PMCID: PMC11385953.

===2021 [https://pubmed.ncbi.nlm.nih.gov/34763266/ Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients]===
*This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.
**Citation: Brodtkorb E, Myren-Svelstad S, Knudsen-Baas KM, Nakken KO, Spigset O. Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients. Epilepsy Res. 2021 Oct 25;178:106792. doi: 10.1016/j.eplepsyres.2021.106792. Epub ahead of print. PMID: 34763266.

===2021 [https://www.pedneur.com/article/S0887-8994(21)00147-8/fulltext Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy]===
*Nevertheless, the two siblings reported here add to the small number of pediatric case reports regarding the successful use of nicotine patches in ADSHE.
*Journal Pre-Proof [https://www.pedneur.com/action/showPdf?pii=S0887-8994%2821%2900147-8 PDF Version]
**Citation: Nguyen SM, Deering L, Nelson GT, McDaniel SS, Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy, Pediatric Neurology (2021), doi:10.1016/j.pediatrneurol.2021.07.006.

===2021 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable."
*"Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031.

===2020 [https://pubmed.ncbi.nlm.nih.gov/33284031/ Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
*"Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction."
*"Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants."
**Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031

===2020 [https://pubmed.ncbi.nlm.nih.gov/32097883/ Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy]===
*"Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions."
**Citation: Lossius K, de Saint Martin A, Myren-Svelstad S, Bjørnvold M, Minken G, Seegmuller C, Valenti Hirsch MP, Chelly J, Steinlein O, Picard F, Brodtkorb E. Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy Behav. 2020 Apr;105:106944. doi: 10.1016/j.yebeh.2020.106944. Epub 2020 Feb 22. PMID: 32097883.

===2018 [https://www.dovepress.com/sleep-related-hypermotor-epilepsy-prevalence-impact-and-management-str-peer-reviewed-fulltext-article-NSS Sleep-related hypermotor epilepsy: prevalence, impact and management strategies]===
*"Seizure frequency improved in a single patient with refractory ADSHE after nicotine transdermal patches treatment.(108) The favorable effect of nicotine on seizure frequency was also described in 9 of 22 patients from two European ADSHE families carrying CHRNA4 mutations.(109) Considering the role of the cholinergic system in arousal regulatory processes, these observations suggested a possible link between nicotine defect, alteration of arousal regulation and seizures in SHE/ADSHE patients. However, despite the reported positive effect of nicotine in reducing seizure frequency, a case–control family study, did not find a higher tendency to smoke tobacco in SHE patients and their relatives compared with the control cases.(110)
**Citation: Menghi V, Bisulli F, Tinuper P, Nobili L. Sleep-related hypermotor epilepsy: prevalence, impact and management strategies. Nat Sci Sleep. 2018 Oct 10;10:317-326. doi: 10.2147/NSS.S152624. PMID: 30349413; PMCID: PMC6186898.

===2015 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433466/ Pearls & Oy-sters: A case of refractory nocturnal seizures]===
*"Due to frequent seizures, there was a paucity of slow-wave sleep and complete absence of REM sleep. On the second day of her hospital admission, a 7-mg nicotine patch was applied about 2–3 hours before bedtime. There was almost complete resolution of clinical and electrical events. The duration of slow-wave sleep increased and REM sleep was recorded. The next morning, the patient felt refreshed and less anxious."
**Citation: Pavlakis PP, Douglass LM. Pearls & Oysters: A case of refractory nocturnal seizures: Putting out fires without smoke. Neurology. 2015 May 5;84(18):e134-6. doi: 10.1212/WNL.0000000000001539. PMID: 25941204; PMCID: PMC4433466.

===2012 [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2012.03715.x Resolution of epileptic encephalopathy following treatment with transdermal nicotine]===
*We report resolution of an epileptic encephalopathy by administration of transdermal nicotine patches in an adolescent with severe nonlesional refractory frontal lobe epilepsy. The 18.5‐year‐old female patient had refractory epilepsy from the age of 11. Recurrent electroencephalography (EEG) recordings showed mostly generalized activity, albeit with right frontal predominance. Almost all antiepileptic medications failed to provide benefit. She developed an encephalopathic state with cognitive decline. The nonlesional frontal lobe epilepsy and a family history of a cousin with nocturnal epilepsy with frontal origin suggested genetic etiology. Transdermal nicotine patches brought complete resolution of the seizures, normalization of the EEG, and a significant improvement in her thinking process and speech organization. Sequencing of the CHRNB2 and CHRNA4 genes did not detect a mutation. Transdermal nicotine patches should be considered in severe pharmacoresistant frontal lobe epilepsy.
*[https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03715.x PDF Version]
**Citation: Zerem, A., Nishri, D., Yosef, Y., Blumkin, L., Lev, D., Leshinsky‐Silver, E., Kivity, S. and Lerman‐Sagie, T. (2013), Resolution of epileptic encephalopathy following treatment with transdermal nicotine. Epilepsia, 54: e13-e15. doi: 10.1111/j.1528-1167.2012.03715.x

===2006 [https://pubmed.ncbi.nlm.nih.gov/16931165/ Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy]===
*"This study indicates that nicotine consumption is an environmental factor that, in many patients with ADNFLE, may influence susceptibility to seizures. A detailed account of tobacco habits should be part of the history. Transdermal nicotine should be considered in pharmacoresistant cases."
*[https://sci-hub.se/10.1016/j.yebeh.2006.07.008 PDF Full study]
**Citation: Brodtkorb E, Picard F. Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Behav. 2006 Nov;9(3):515-20. doi: 10.1016/j.yebeh.2006.07.008. Epub 2006 Aug 22. PMID: 16931165.

===2003 [https://onlinelibrary.wiley.com/doi/full/10.1046/j.1528-1157.2003.58102.x-i1?sid=nlm%3Apubmed Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study]===
*In this individual with refractory [[Special:MyLanguage/Abbreviations|'''ADNFLE''']], nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
*[https://sci-hub.st/https://doi.org/10.1046/j.1528-1157.2003.58102.x-i1 PDF Version]
**Citation: Willoughby, J.O., Pope, K.J. and Eaton, V. (2003), Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study. Epilepsia, 44: 1238-1240. doi: 10.1046/j.1528-1157.2003.58102.x-i1
 

='''Sepsis/Septic/endotoxemia/infection'''=
===2024 [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===
*Animal Study
*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.
**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.
***Funding: None

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
*Review includes human and animal studies.
*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."
*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."
*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."
**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314
***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2014 [https://academic.oup.com/jid/article/209/10/1668/855517#78932729 Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation]===
*Animal study
*In conclusion, stimulation of α7nAChR by nicotine improves mortality rates and MODS during sepsis. This protective effect of nicotine can be associated with the inhibition of TLR4 overexpression through the PI3K/Akt signaling pathway. Although the therapeutic potential of nicotine is still limited by its nonspecific effects, this study may provide an impetus for further development of therapeutic strategies for modifying the cholinergic antiinflammatory pathway in the treatment of various inflammatory diseases.
**Citation: Kim TH, Kim SJ, Lee SM. Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation. J Infect Dis. 2014 May 15;209(10):1668-77. doi: 10.1093/infdis/jit669. Epub 2013 Dec 1. Erratum in: J Infect Dis. 2015 Mar 1;211(5):851. doi: 10.1093/infdis/jiu824. PMID: 24298024.
***Acknowledgement: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (NRF-2013R1A1A3008145).

===2011 [https://pubmed.ncbi.nlm.nih.gov/20805763/ Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide]===
*Animal Study
*The results suggested that both carbachol and nicotine play a role in the anti-inflammatory process and organ function protection through the α7 subunit of nicotinic cholinergic receptor.
*[https://sci-hub.st/10.1097/TA.0b013e3181e9732d PDF Full Paper]
**Citation: Zhou G, Hu S, Lv Y, Song Q, Zou X, Sheng Z. Carbachol alleviates rat cytokine release and organ dysfunction induced by lipopolysaccharide. J Trauma. 2011 Jul;71(1):157-62. doi: 10.1097/TA.0b013e3181e9732d. PMID: 20805763.
***Acknowledgement: From the Laboratory of Shock and Organ Dysfunction (G.Z., S.H., Y.L., Q.S., X.Z., Z.S.), Burn Institute, the First Hospital Affiliated to the People’s Liberation Army General Hospital, Beijing, China.

===2005 [https://academic.oup.com/jid/article/191/12/2138/842542 The Cholinergic Anti-Inflammatory Pathway Regulates the Host Response during Septic Peritonitis]===
*Animal Study
*"Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired."
**Citation: van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis. 2005 Jun 15;191(12):2138-48. doi: 10.1086/430323. Epub 2005 May 10. PMID: 15898001.
***Acknowledgement: Financial support: Academic Medical Center, Amsterdam, The Netherlands. Potential conflicts of interest: K.J.T. is cofounder of Critical Therapeutics Inc., a pharmaceutical company developing potential future treatment modalities based on the cholinergic anti-inflammatory pathway.

='''Sleep'''=

==Apnea==

===1991: [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against sleep apnea (other diseases / issues mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

===1985: [https://pubmed.ncbi.nlm.nih.gov/3965253/ Nicotine: a different approach to treatment of obstructive sleep apnea]===
*Reduced upper airway muscle activity may contribute to the occurrence of obstructive apneas during sleep. There is no uniformly successful treatment of these apneas, and it is possible that agents which increase upper airway muscle activity could reduce the occurrence of obstruction during sleep. Nicotine, a known stimulant of breathing, also increases the activity of muscles which dilate the upper airway proportionally more than it does ventilation. Hence, we evaluated the effect of nicotine on apneas during the first two hours of sleep in eight patients with sleep apnea syndrome. It was concluded that nicotine reduces apneas during the early hours of sleep, and this effect may be caused by its stimulating action on upper airway muscles.
*[https://sci-hub.se/10.1378/chest.87.1.11 PDF Version]
**Citation: Gothe B, Strohl KP, Levin S, Cherniack NS. Nicotine: a different approach to treatment of obstructive sleep apnea. Chest. 1985 Jan;87(1):11-7. doi: 10.1378/chest.87.1.11. PMID: 3965253.
***Acknowledgement: None found

==REM==

===2017: [https://onlinelibrary.wiley.com/doi/10.1002/brb3.704 Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus]===
*Animal study
*MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein.
**Citation: Abd Rashid N, Hapidin H, Abdullah H, Ismail Z, Long I. Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus. Brain Behav. 2017; 7:e00704. https://doi.org/10.1002/brb3.704
***Acknowledgement: This study was supported by the Universiti Sains Malaysia (USM) Short-Term Grant Scheme (304/PPSK/61312093), USM Research University grants (RUI) (1001/PPSK/812139) and Fundamental Research Grant Scheme (FRGS) (203/PPSK/6171153).

===2011: [https://onlinelibrary.wiley.com/doi/10.1002/hipo.20806 Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat]===
*Animal Study
*However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.
*[https://www.academia.edu/18461315/Acute_nicotine_treatment_prevents_REM_sleep_deprivation_induced_learning_and_memory_impairment_in_rat PDF Full paper]
**Citation: Aleisa, A.M., Helal, G., Alhaider, I.A., Alzoubi, K.H., Srivareerat, M., Tran, T.T., Al-Rejaie, S.S. and Alkadhi, K.A. (2011), Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat. Hippocampus, 21: 899-909. https://doi.org/10.1002/hipo.20806
***Acknowledgement: None found
 

='''Smoking Cessation / Preventing Relapse'''=
===Resource Doc: [https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO - Myth of the month: Ecigs and snus don’t help smokers quit]===
*Links and conclusions of studies formatted to fit the character limits on Twitter

===[https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]===
*This wiki page shows over 70 studies demonstrating these products help people stop smoking.
 

='''Spinal Cord Injury'''=
===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===
*Animal Study
*Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in [[Special:MyLanguage/Abbreviations|'''spinal cord injury (SCI)''']].
*The results of the present study indicate that [[Special:MyLanguage/Abbreviations|'''iNOS''']] is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
*[https://sci-hub.st/10.1002/jnr.21901 PDF Version]
*Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
*Acknowledgements: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.
*Key words: spinal cord injury; nicotine; neuronal nicotinic receptors; oxidative stress; inflammatory responses; nitric oxide synthase

= Stroke =

=== 2025: '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf034/8005730?redirectedFrom=fulltext&login=false The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]''' ===

* Animal study (mice)
* These results demonstrate that nicotine treatment could alleviates the IS-compromised integrity of BBB by regulating the Wnt signal pathway through α7 nAChR.
* The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke.
* Qianqian Pang, Xinyang Yan, Zheng Chen, Liang Yun, Jiang Qian, Zeyi Dong, Miao Wang, Wei Deng, Yao Fu, Tao Hai, Zhichao Chen, Xianfang Rong: Nicotine & Tobacco Research, ntaf034, <nowiki>https://doi.org/10.1093/ntr/ntaf034</nowiki>

='''Tobacco Use Disorder'''=

===2023: [https://link.springer.com/article/10.1007/s11606-023-08137-z Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===
*The remarkable decline in cigarette smoking since 1964 has plateaued; approximately 12.5% of Americans still smoke. People who continue to smoke are largely members of marginalized groups, such as people with behavioral health conditions (BHC), encompassing both mental health and substance use disorders.
*Although not a panacea, electronic cigarettes may represent a powerful harm reduction tool amongst subpopulations traditionally left behind in conventional smoking cessation movements. The argument in favor of studies of electronic cigarettes as a smoking cessation, harm reduction intervention in people with BHC is multi-faceted. People with BHC have higher levels of smoking burdens and nicotine addiction compared to the general population, and they quit at lower rates. Unlike NRT, the nicotine delivery from an electronic cigarette mimics the nicotine pharmacokinetics of tobacco cigarettes unaccompanied by high levels of toxicants and carcinogens.22 Thus, electronic cigarettes may be well positioned to satisfy this nicotine addiction, and mitigate the intense nicotine withdrawal symptoms that sabotage many quit attempts. People with BHC want to stop smoking, and indicators suggest that electronic cigarettes would be an acceptable and well-received intervention.
**Citation: Vuong, J.T., Ruedisueli, I., Beaudin, C.S. et al. Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders. J GEN INTERN MED 38, 1970–1974 (2023). https://doi.org/10.1007/s11606-023-08137-z
***Acknowledgement: None stated

='''Tourette's Syndrome'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===
*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.
***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012 [https://pubmed.ncbi.nlm.nih.gov/22776623/ Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond]===
* The article presents a mini-review of studies on TS and depression over the past 25 years.
* It summarizes the studies on the behavioral biology of the basal ganglia and its neurotransmitters.
* It describes research with TS patients to evaluate the therapeutics of nicotine and mecamylamine.
* [https://sci-hub.se/10.1016/j.physbeh.2012.06.023 PDF Version]
*Citation: Sanberg, P. R., Vindrola-Padros, C., & Shytle, R. D. (2012). Translating laboratory discovery to the clinic: From nicotine and mecamylamine to Tourette’s, depression, and beyond. Physiology & Behavior, 107(5), 801–808. doi:10.1016/j.physbeh.2012.06.023
*Acknowledgement: Paul R. Sanberg and R. Douglas Shytle are inventors on patents related to technology described herein and licensed from the University of South Florida to Targacept, Inc. Because of the historical nature of this article, the authors included a number of self-citations required for a chronological discussion.

===2004 [https://pubmed.ncbi.nlm.nih.gov/15132126/ Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome]===
*In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 hours, but counteracted [https://en.wikipedia.org/wiki/P300_(neuroscience) ERP-P300] signs of diminished attention seen 2 weeks following placebo treatment.
*Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention.
*[https://sci-hub.st/10.1016/j.eurpsy.2003.11.002 PDF Version ]
*Citation: Howson, A. L., Batth, S., Ilivitsky, V., Boisjoli, A., Jaworski, M., Mahoney, C., & Knott, V. J. (2004). Clinical and attentional effects of acute nicotine treatment in Tourette’s syndrome. European Psychiatry, 19(2), 102–112. doi:10.1016/j.eurpsy.2003.11.002
*Acknowledgement: This study was supported with a grant from the Tourette Syndrome Association (USA), and patient recruitment was aided by the Ottawa chapter of the Tourette Syndrome Foundation of Canada.

===2001 [https://pubmed.ncbi.nlm.nih.gov/11681767/ Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study]===
*[[Special:MyLanguage/Abbreviations|'''Transdermal nicotine (TNP)''']] was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder
*[https://www.researchgate.net/profile/Paul_Sanberg/publication/11670769_Transdermal_Nicotine_and_Haloperidol_in_Tourette's_Disorder/links/5be32624299bf1124fc2d86a/Transdermal-Nicotine-and-Haloperidol-in-Tourettes-Disorder.pdf PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Wilkinson BJ, McConville B, Sanberg PR. Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study. J Clin Psychiatry. 2001 Sep;62(9):707-14. doi: 10.4088/jcp.v62n0908. PMID: 11681767.

===1997 [https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994 Nicotine for the treatment of Tourette's syndrome]===
*Within 24 hr of the application of a single 7-mg [[Special:MyLanguage/Abbreviations|'''TNP (nicotine patch)''']], the severity and frequency of tic symptoms is significantly decreased over baseline. This response is rapid, often reaching its maximum in the first 3 hr after application of a single patch. The duration of therapeutic effect of a single 7-mg TNP is variable and may last for about l-2 weeks.
*Application of a 7-mg TNP to children and adolescents with [[Special:MyLanguage/Abbreviations|'''TS''']] appears to be clinically safe, with transient side effects. However, no child under 8 years of age and weighing less than 25 kg was considered for TNP treatment.
*[https://sci-hub.st/https://www.sciencedirect.com/science/article/abs/pii/S0163725896001994?via%3Dihub PDF Version]
*Citation: Paul R. Sanberg, Archie A. Silver, R.Doug Shytle, Mary Katherine Philipp, David W. Cahill, Harold M. Fogelson, Brian J. McConville, Nicotine for the treatment of Tourette's syndrome, Pharmacology & Therapeutics, Volume 74, Issue 1, 1997, Pages 21-25, ISSN 0163-7258, doi.org/10.1016/S0163-7258(96)00199-4.
* Acknowledgements-This review was supported, in part, by grants from the Tourette Syndrome Association, The National Institute of Neurological Disease and Stroke (ROl NS 32067sOlAl) and the Smokeless Tobacco Research Council.
*Keywords: Nicotine; Tourette's syndrome; tics; neuropsychiatric disorders

===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
*nicotine may have therapeutic uses in the treatment of [[Special:MyLanguage/Abbreviations|'''Gilles de la Tourette’s syndrome (TS)''']].
*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]
*Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

=== 1996 [https://pubmed.ncbi.nlm.nih.gov/8973070/ Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome]===
* Sixteen Tourette's syndrome patients, aged 9 to 15 years, whose symptoms were not controlled with neuroleptics, were followed for various lengths of time after the application of one 7 mg [[Special:MyLanguage/Abbreviations|'''transdermal nicotine patch (TNP)''']] for 24 hours. While there was a broad range in individual response, application of the TNP produced significant reductions in [[Special:MyLanguage/Abbreviations|'''Yale Global Tic Severity Scale (YGTSS)''']] scores relative to baseline, with an average duration of effect lasting between 1 and 2 weeks. Side effects, for the most part, were transient.
*Eleven patients had greater percentage changes after the second TNP than after the first TNP
*[https://sci-hub.st/10.1097/00004583-199612000-00015 PDF Version]
*Citation: Silver AA, Shytle RD, Philipp MK, Sanberg PR. Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1996 Dec;35(12):1631-6. doi: 10.1097/00004583-199612000-00015. PMID: 8973070.

===1992 [https://pubmed.ncbi.nlm.nih.gov/1643197/ The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder]===
*In this study, nicotine markedly potentiated haloperidol effects in treating [[Special:MyLanguage/Abbreviations|'''TD''']], and showed lesser effects on TD when used alone.
*[https://sci-hub.st/10.1016/0006-3223(92)90315-q PDF Version]
* Citation: McConville BJ, Sanberg PR, Fogelson MH, King J, Cirino P, Parker KW, Norman AB. The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder. Biol Psychiatry. 1992 Apr 15;31(8):832-40. doi: 10.1016/0006-3223(92)90315-q. PMID: 1643197.
*Acknowledgements: Supported in part by grants from the Smokeless Tobacco Research Council, Inc., the Tourette Syndrome Association, and Merrell Dow Pharmaceuticals. The authors thank Roger Stuebing, B.S.M.E., M.S.I.E., and Sunny Y. Lu, M.D., Ph.D. for statistical advice and Merrell Dow Pharmaceuticals for supplying both Nicoreue® gum and placebo nicotine gum.

='''Weight Loss / Appetite Control / Metabolism / Obesity'''=

===2024 Article [https://web.archive.org/web/20241204102835/https://tobaccoreporter.com/2024/12/03/slim-chances/ Harm reduction, smoking cessation and weight]====
*"Nicotine influences eating and weight in multiple ways, from hormones to microbiomes to taste perceptions. The bottom line: Nicotine raises the metabolic rate while also depressing appetite."

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
**Citation: Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database of Systematic Reviews 2021, Issue 10. Art. No.: CD006219. DOI: 10.1002/14651858.CD006219.pub4. Accessed 03 July 2025.
***[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/information Acknowledgement]

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
*Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.
*Low-grade inflammation is a key feature of obesity and links obesity to insulin resistance, impaired glucose tolerance and even diabetes.
*Overall, these findings suggest that nicotine and specific α7nAChR agonists may be beneficial in the prevention and treatment of obesity-induced inflammation and insulin resistance. However, there is also evidence that heavy smoking affects body fat distribution that is associated with central obesity and insulin resistance. Moreover, smoking appears to aggravate insulin resistance in persons with type 2 diabetes and to impair glycemic control.
*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
**Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129
***Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
***Acknowledgement: None stated

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
* When chronically taken, nicotine may result in reduction of body weight
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF version]
**Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
***Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
 

='''Suggested additions to this page'''=

===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.

===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

===[https://www.researchgate.net/publication/325159226_Resolution_of_chronic_rhinitis_to_staphylococcus_aureus_in_a_non-smoker_who_started_to_use_glycerine_based_e-cigarettes_Antibacterial_effects_of_vaping Resolution of chronic rhinitis to staphylococcus aureus in a non-smoker who started to use glycerine based e-cigarettes: Antibacterial effects of vaping?]===

===2019: [https://medium.com/parkinsons-uk/protecting-brain-cells-the-story-of-nicotine-b3b51f5b8259 Protecting brain cells — the story of nicotine]===
*[https://web.archive.org/web/20221021040501/https://www.parkinsons.org.uk/nicotine-good-bad-and-ugly Nicotine - Good, Bad, Ugly]

===2017 [https://www.ncbi.nlm.nih.gov/pubmed/27940486 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease]===
*Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
*different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German) 'Cognition: nicotine versus neuropsychiatric disorders' ===

===Dr. Newhouse [http://mindstudy.org/news Mind Study]===

===2010 [https://pubmed.ncbi.nlm.nih.gov/20414766/ Meta-analysis of the acute effects of nicotine and smoking on human performance] and 2012 [https://n.neurology.org/content/78/2/91.short Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial]===
*Clinical studies suggest some cognitive improvements as a result of nicotine.

===2021 [https://www.dovepress.com/effectiveness-and-safety-profile-of-alternative-tobacco-and-nicotine-p-peer-reviewed-fulltext-article-JMDH Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review]===

===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].”
https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===

===To do: Go through the references for nicotine related studies===
====2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]====

='''More Information'''=

*[[Special:MyLanguage/Nicotine Studies|'''List of researchers''']] studying nicotine / tobacco harm reduction

*If you'd prefer someone else to add a study to a topic, there is a "topic" called "Suggested studies to add to this page". You may put the link in that section for one of the regular page editors to address.

*'''PAGE EDITORS - Please only add Studies, Surveys, Papers in this format to keep page consistent for all viewers.'''
**Topic
**Note here if animal study (leave blank if not)
**Year (list new to old) Name of Study (In link format to the study)
**Brief Summary
**Link to PDF Version
**Citation
**Acknowledgements (funded by, helped by)
**Keywords
**Other
[[Category:Studies, Surveys, and Papers]]
[[Category:THR product]]
[[Category:THR Stories]]

Nicotine - Retracted Studies, Papers, and Articles

2026-03-13T14:08:53Z

Skip: /* 2025: Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey */

[[File:Corrections.png|center|]]
 

<big>'''On this page, we'll explore how mistakes in published works can happen, log commentaries on some published works, and list some examples of retracted papers.'''</big>

=How Mistakes Can Happen=

==Journals==

===2024: (Preprint) [https://www.preprints.org/manuscript/202410.2456/v2 Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy]===
*"This review explores methodological considerations for maximizing the precision and accuracy of observational cohort studies assessing the risk profiles of tobacco and nicotine products. These considerations, informed by the ROBINS framework for minimizing statistical bias, are anchored in a comprehensive characterization of exposure to all tobacco products currently or formerly used, with corroboration of dose-response relationships."
**Citation: Cohen, G., & Cook, S. (2024). Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy. Preprints. https://doi.org/10.20944/preprints202410.2456.v2

===2024: [https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1433626/full Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols]===
*"Updating and improving testing standards to incorporate basic conditions of experimental quality is necessary to achieve a more objective evaluation of the risk profile of ECs, which will provide valuable information to all stakeholders (consumers, health professionals, regulators, and the industries themselves)."
**Citation: Sussman RA, Sipala FM, Ronsisvalle S and Soulet S (2024) Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols. Front. Chem. 12:1433626. doi: 10.3389/fchem.2024.1433626

===2022: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis]===
*"Studies based on cross-sectional data with no information on age of e-cigarette initiation and age of diagnosis invariably overestimate associations by including cases that were diagnosed before e-cigarette exposure. Although the authors of those studies did not make causal claims in the reports, university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."
**Citation: Rodu B, Plurphanswat N. Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Intern Emerg Med. 2023 Jan;18(1):319-323. doi: 10.1007/s11739-022-03141-3. Epub 2022 Nov 25. PMID: 36434423.
*Commentary: [https://reason.com/wp-content/uploads/2022/12/Polosa-Commentary-IAEM-2022.pdf A tale of flawed e‑cigarette research undetected by defective peer review process]
*Article: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Diseases That Studies Linked to E-Cigarettes Generally Were Diagnosed Before Subjects Began Vaping]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018638/ Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research]===
*Conclusion: "Our critical appraisal reveals common, preventable flaws, the identification of which may provide guidance to researchers, reviewers, scientific editor, journalists, and policy makers. One striking result of the review is that a large portion of the high-ranking papers came out of US-dominated research institutions whose funders are unsupportive of a tobacco harm reduction agenda..."
**Citation: Hajat C, Stein E, Selya A, Polosa R; CoEHAR study group. Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research. Intern Emerg Med. 2022 Apr;17(3):887-909. doi: 10.1007/s11739-022-02967-1. Epub 2022 Mar 24. Erratum in: Intern Emerg Med. 2022 Aug;17(5):1561. PMID: 35325394; PMCID: PMC9018638.
*Article: [https://filtermag.org/vaping-research-quality/ Researchers Expose the Pitiful Quality of Highly Cited Vaping Studies]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506048/ A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol]===
*Abstract: "The inhalation of metallic compounds in e-cigarette (EC) aerosol emissions presents legitimate concerns of potential harms for users. We provide a critical review of laboratory studies published after 2017 on metal contents in EC aerosol, focusing on the consistency between their experimental design, real life device usage and appropriate evaluation of exposure risks. All experiments reporting levels above toxicological markers for some metals (e.g., nickel, lead, copper, manganese) exhibited the following experimental flaws: (i) high powered sub-ohm tank devices tested by means of puffing protocols whose airflows and puff volumes are conceived and appropriate for low powered devices; this testing necessarily involves overheating conditions that favor the production of toxicants and generate aerosols that are likely repellent to human users; (ii) miscalculation of exposure levels from experimental outcomes; (iii) pods and tank devices acquired months and years before the experiments, so that corrosion effects cannot be ruled out; (iv) failure to disclose important information on the characteristics of pods and tank devices, on the experimental methodology and on the resulting outcomes, thus hindering the interpretation of results and the possibility of replication"
**Citation: Soulet S, Sussman RA. A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol. Toxics. 2022 Aug 29;10(9):510. doi: 10.3390/toxics10090510. PMID: 36136475; PMCID: PMC9506048.

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787926/ Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===
*Abstract: "We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and “dry puffs”. The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design."
**Citation: Soulet S, Sussman RA. Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions. Toxics. 2022 Nov 22;10(12):714. doi: 10.3390/toxics10120714. PMID: 36548547; PMCID: PMC9787926.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769337/ Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations]===
*Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context.
**Citation: Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. PMID: 29375395; PMCID: PMC5769337.

===2017: [https://pubmed.ncbi.nlm.nih.gov/28864295/ E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions]===
*The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
**Citation: Farsalinos KE, Voudris V, Spyrou A, Poulas K. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions. Food Chem Toxicol. 2017 Nov;109(Pt 1):90-94. doi: 10.1016/j.fct.2017.08.044. Epub 2017 Aug 31. PMID: 28864295.

===2015: [https://pubmed.ncbi.nlm.nih.gov/25996087/ E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions]===
*Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid.
**Citation: Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. PMID: 25996087.

==Articles/Blogs==

===2024: [https://www.thefirebreak.org/p/formaldehyde-in-vapes-exposing-another Formaldehyde In Vapes? Exposing Another Chemical Scare]===
*"The same can be said of smokers who are discouraged from switching to vapes. In the name of reducing formaldehyde exposure that is already vanishingly small, the anti-vaping warriors have effectively urged people to continue using tobacco products that contain vastly higher quantities of the compound and kill some six million users annually. They manipulate public policy and deprive people–in this case smokers looking to quit–of products that could preserve their health and even save their lives."

===2024: [https://rodutobaccotruth.blogspot.com/2024/04/are-vape-aerosols-really-toxic.html Are Vape Aerosols Really Toxic?]===
*Addresses several studies

=Science Hygiene, the efforts to correct mistakes or seek retractions by experts=
*'''Notes:'''
**'''Dates denote when comments were published, not the paper's publication date.'''
**'''Clicking the link following "Comments RE" takes you to the comment. The article the comment is addressing will be linked under "Referring to."'''

==Addiction / Dependence / Use==
*To learn more about addiction/dependence, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine_-_Addiction/Dependence Nicotine - Addiction/Dependence]

===2024: Comments RE: [https://pubpeer.com/publications/40A35E1B6BCE23874F886C76971576 E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective]===
*Waa’s “Indigenous perspective” on e‐cigarette policies claiming Māori (the Indigenous people of New Zealand) were being exploited [1] omits some important context... (Lists examples)... Finally, Māori people have diverse views on vaping. For example, the Manager of the National Tobacco Control Advocacy Service, Hapai Te Hauora said in 2019, “Do you know who has a vested interest in vaping? Anyone who is sick of losing 5,000 whānau [family] members a year to tobacco; anyone who acknowledges the growing body of research showing vaping is helping many to break free of their tobacco addiction; anyone who cares about our people”. (Mendelsohn, Glover)
**Referring to: Waa A. E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective. Addiction. 2024 May 24. Epub ahead of print. PMID: 38794822. [https://onlinelibrary.wiley.com/doi/10.1111/add.16573 doi: 10.1111/add.16573].
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16462 E-cigarettes: A framework for comparative history and policy]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16660 Evidence and policy is certainly more complex than it seems]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16597 A tobacco control policy analysis framework that extends into the future]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16577 Adopting the Berridge et al.: Framework to understand differences in the e-cigarette policy between the Nordic countries]

===2024: Comments RE: [https://pubpeer.com/publications/E128EE4F19CD39411FAFDDB6A88FED Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity]===
*Despite the authors correcting recognizing that “no trends… should be inferred” between 2020 and 2021, they infer trends between 2021 and 2022, thus making the very same error, as the artifact relates to NYTS 2021 alone, not 2021 and every year thereafter. (Selya)
**Referring to: Mattingly DT, Hart JL. Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity. JAMA Netw Open. 2024;7(2):e2354872. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814427 doi:10.1001/jamanetworkopen.2023.54872]

===2024: Comments RE: [https://pubpeer.com/publications/DEF986999C6287FCD8FD4048A0B8EE Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022]===
*"Overall, Zhang et al. improperly conclude that there is a true uptick in dual- and poly-use of nicotine and tobacco in NYTS, but did not attribute any of their findings to a well-documented methodological artifact in NYTS 2021 which renders the findings inconclusive, as (in the words of official NYTS publications) 'differences between estimates might be due to changes in methodology, actual behavior, or both.' ” (Selya)
**Referring To: Zhang, B., Bannon, O., Chen, D. T., & Filippidis, F. T. (2024). Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022. Addictive Behaviors, 152, 107970. [https://www.sciencedirect.com/science/article/pii/S0306460324000194 https://doi.org/10.1016/j.addbeh.2024.107970]

===2023: Comments RE: [https://pubpeer.com/publications/3BF65B1CBECA15D0EC1068CF8628BC#2 Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth]===
*"Readers may be interested to know that there is now a comment to the Pierce et al paper from Shiffman and Hannon. The commenters raise questions about the conclusions drawn by the original authors and report alternative analyses of the same dataset." (Gitchell)
*"To this last point, Pierce and Strong’s response now reports a relevant analysis, and it directly contradicts their assertion in the original paper: they demonstrate that dependence among JUUL users in each age cohort was not different from dependence in users of other ENDS brands (though the trend is evidently for lower dependence among JUUL users)." (Shiffman)
**Referring To: Pierce JP, Leas EC, Strong DR. Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth. Pediatrics. 2023 Apr 1;151(4):e2022059158. PMID: 36942497. doi: https://doi.org/10.1542/peds.2022-059158

===2022: Comments RE: [https://pubpeer.com/publications/1FF8B75DFC81492DEBC8E214F63098 Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study]===
*A re-analysis of the data by Foxon & Shiffman (2) revealed that those analyses did not include replicate weights as specified in guidance from the PATH study team. Foxon & Shiffman (2) show that when the above analyses are performed with the replicate weights included, the associations above are statistically non-significant. (Foxon, Shiffman)
*(2) [https://www.mdpi.com/1660-4601/20/18/6715 Full Comment]
**Referring to: Wang Y, Duan Z, Weaver SR, Popova L, Spears CA, Ashley DL, Pechacek TF, Eriksen MP, Huang J. Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study. International Journal of Environmental Research and Public Health. 2022; 19(17):10837. [https://doi.org/10.3390/ijerph191710837 https://doi.org/10.3390/ijerph191710837]

===2021: Comments RE: [https://pubpeer.com/publications/57A74561DC4B1B43B91E18A95A24A5 Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users]===
*In summary, by imputing respondents who reported that they “don’t know” which ENDS brand they used to the non-JUUL group even if they may have used JUUL, and by relying on ‘any’ JUUL use definitions which defined as JUUL users those who “usually” used a different ENDS brand, the original analysis systematically biases against the focal brand (JUUL) being studied. (Foxon, Shiffman)
*In summary, the results of Mantey et al. are invalid, because they were based on a definition of JUUL use that is not justified by the brand information in the 2020 National Youth Tobacco Survey.(Rodu)
**Referring to: Mantey DS, Case KR, Omega-Njemnobi O, Springer AE, Kelder SH. Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users. Drug Alcohol Depend. 2021 Nov 1;228:109078. Epub 2021 Sep 24. PMID: 34614433; PMCID: PMC8595823. [https://doi.org/10.1016/j.drugalcdep.2021.109078 https://doi.org/10.1016/j.drugalcdep.2021.109078]

===2019: Comments RE: [https://pubpeer.com/publications/1F7BA5A2DEC4EF71CA4E7F34C69806 Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys]===
*These (improbable) increases conflict with official data from Statistics Canada that were released shortly after the publication of the paper drawn from the Canadian Community Health Survey, with a representative sample of 65,000. (Bates)
*The Counterfactual: [https://clivebates.com/canada-takes-a-wrong-turn-after-a-flawed-paper-induces-moral-panic-about-youth-vaping-and-smoking/ Canada takes a wrong turn after a flawed paper induces moral panic about youth vaping and smoking]
**Referring to: Hammond D, Reid JL, Rynard VL, Fong GT, Cummings KM, McNeill A, Hitchman S, Thrasher JF, Goniewicz ML, Bansal-Travers M, O'Connor R, Levy D, Borland R, White CM. Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys. BMJ. 2019 Jun 20;365:l2219. Erratum in: BMJ. 2020 Jul 10;370:m2579. PMID: 31221636; PMCID: PMC6582265. [https://doi.org/10.1136/bmj.l2219 doi: 10.1136/bmj.l2219]
**[https://www.bmj.com/content/370/bmj.m2579 Corrections]: "The authors of this paper (BMJ 2019;365:l2219, doi:10.1136/bmj.l2219, published 20 June 2019) have provided an update on estimates of smoking among adolescents and vaping from the ITC Youth and Vaping Surveys conducted in Canada, England, and the United States (see supplementary file for details).
**I note with interest that another paper in BMJ includes the same red-box Correction. However with this one, upon clicking, it opens a page displaying a direct and complete explanation of the correction and a pledge that the paper itself will be updated (it has been). It would be welcome if the journal would apply the same level of rigor to the Hammond et al paper (Gitchell).

===2018: Comments RE: [https://pubpeer.com/publications/58B4D5D27C6A7C45EE3A094D324368 Prevalence and correlates of JUUL use among a national sample of youth and young adults]===
*The results from this article are uninformative, because the authors did not include simple crosstabs of the raw numbers showing the overlap in current use of ENDS, JUUL and combustible products. They failed to denote current ENDS use in the model for Table two. (Rodu)
**Referring to: Vallone DM, Bennett M, Xiao H, Pitzer L, Hair EC. Prevalence and correlates of JUUL use among a national sample of youth and young adults. Tob Control. 2019 Nov;28(6):603-609. Epub 2018 Oct 29. PMID: 30377241. [https://doi.org/10.1136/tobaccocontrol-2018-054693 https://doi.org/10.1136/tobaccocontrol-2018-054693]

===2014: Comments RE: [https://sci-hub.wf/10.1001/jamapediatrics.2014.733 Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents]===
*"In a cross-sectional study, the observed relationship between e-cigarette use and higher and more sustained levels of smoking does not imply causation. Moreover, such studies do not take into account other population characteristics, which may play a crucial role when determining potential causation.2,3 Although the authors acknowledged this limitation in the text, they ended up drawing a conclusion that misleads the public into thinking e-cigarettes are leading to smoking initiation and addiction among adolescents." (Farsalinos, Polosa)
*"Although Dutra and Glantz highlighted an important trend in e-cigarette use among our nation’s youth, failing to consider e-cigarette use in the context of other tobacco products may place undue emphasis on e-cigarettes, overshadowing the importance of the current use of multiple tobacco products as well as experimentation with cigars, smokeless tobacco, and hookah in this population." (Delnevo, Bover Manderski,Giovino)
**Referring to: Dutra LM, Glantz SA. Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. JAMA Pediatr. 2014;168(7):610–617. [https://jamanetwork.com/journals/jamapediatrics/fullarticle/1840772 doi:10.1001/jamapediatrics.2013.5488]

==Cancer==

===2024: Comments RE: [https://pubpeer.com/publications/AC3CFEABA70EC0D0AEBD1568368478 Vaping, Smoking and Lung Cancer Risk]===
*There are 10 issues with this study - Reverse Causality, Combining of Current & Ex-Smokers, Temporal Confounding, Contradiction with National Lung Cancer Trends, Absence of a Dose-Response Relationship, Unclear Definition and Consistency of Use Measures, Recall and Reporting Bias, Biological Implausibility, Uniform Effect Across Histologic Cell Types, Age at smoking initiation not adjusted for. [see commentary for further details] (Herzig)
**Referring to: Bittoni MA, Carbone DP, Harris RE (2024) Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther 9: 10229. https://doi.org/10.29011/2574-710X.10229.

==Cardiovascular==

===2024: Comments RE: [https://pubpeer.com/publications/CD0E2CD6E82EB2F69173F5A1193331#1 Electronic Cigarette Use and Myocardial Infarction]===
*"The research question posed is an important one, since the number of people who have never smoked and who report using e-cigarettes appears to have increased in recent years. However, we are concerned that the methods used in the Alzahrani study [1] make the reported findings highly suspect and the conclusion reached unlikely. This includes: 1) temporality concerns; 2) measurement, diagnosis, and biological plausibility concerns; 3) sample size concerns; 4) model design concerns; and 5) uncareful language." (Foxon, Polosa, Niaura, Cummings, Siegel, Benowitz)
**[https://twitter.com/FloeFoxon/status/1748004148987965469 Tweetorial]
*See also: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055619/ Questionable Effects of Electronic Cigarette Use on Cardiovascular Diseases From the National Health Interview Survey (NHIS, 2014-2021)]
**The study by Alzahrani made erroneous claims and overstated the association between e-cigarettes and myocardial infarction. Our replication shows that the association is driven by age and there were no statistically significant associations with other cardiovascular diseases, coronary heart diseases, and stroke.
***Referring to: Alzahrani T (November 06, 2023) Electronic Cigarette Use and Myocardial Infarction. Cureus 15(11): e48402. [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction doi:10.7759/cureus.48402]

===2022: Comments RE: [https://pubpeer.com/publications/B1574611ED725601C17C3766DB164E Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular disease. A recent analysis by my research group of data from the Population Assessment of Tobacco and Health, which contains this essential temporal information, provides definitive evidence that the results from Osei et al. are deficient and unreliable." (Rodu)
**Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Benjamin EJ, Hall ME, DeFilippis AP, Stokes A, Bhatnagar A, Nasir K, Blaha MJ. Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers. Am J Med. 2019 Aug;132(8):949-954.e2. doi: [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction#!/ 10.1016/j.amjmed.2019.02.016]. Epub 2019 Mar 8. PMID: 30853474.

===2022: Comments RE: [https://pubpeer.com/publications/D075EB2EED18CA0311BAC77C783777 Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use]===
*"The study by Vindhyal et al. used the National Health Interview Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
**Referring to: Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS. Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use. Cureus. 2020 Aug 8;12(8):e9618. [https://pubmed.ncbi.nlm.nih.gov/32923219/ doi: 10.7759/cureus.9618]. PMID: 32923219; PMCID: PMC7478662.

===2020: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-smoking-vaping-and-stroke-risk/ Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults]===
*“These findings arise from subgroup analysis involving multiple hypothesis tests and are therefore unreliable. Contrary to the authors’ claim, this study provides no evidence that vaping increases the risk of stroke accrued from smoking tobacco.” (Britton)
*“While the paper itself is careful in interpreting the finding, the press release is grossly misleading. The study provides no justification for the claim that vaping increases the risk of stroke.” (Hajek)
*"While this paper highlights the need to continue studying the potential health effects of e-cigarette use, the results should be interpreted with caution as the observed associations may be simply due to unmeasured confounding and reverse causality.” (Shahab)
**Referring to: Parekh T, Pemmasani S, Desai R. Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults. Am J Prev Med. 2020 Mar;58(3):446-452. [https://pubmed.ncbi.nlm.nih.gov/31924460/ doi: 10.1016/j.amepre.2019.10.008]. Epub 2020 Jan 7. PMID: 31924460.

===2020-2022: Comments RE: [https://pubpeer.com/publications/E4180AE40B2A0F076D7D07CE0B7961 Association Between Electronic Cigarette Use and Myocardial Infarction]===
*Multiple comments:
**"The study by Alzahrani et al. used data from the National Health Interview Survey, which contains no information about when participants started to smoke or vape, and when they were diagnosed with a myocardial infarction." (Rodu)
**"E-cigarettes first appeared in the US at about 2009 and their use picked up from about 2013. In the cohorts from 2014 and 2016 that this study used, most participants with a history of MI can be expected to have had their MI before they tried e-cigarettes...The authors’ conclusions are thus misleading on an important public health issue. The article has been used e.g. to claim that vaping increases risk of cardiovascular disease by the WHO Director Ghebreyesus (DOI: 10.1016/S0140-6736(19)31730-1). The data that the paper reports show no such thing." (Hajek)
*See also: [https://www.ajpmonline.org/article/S0749-3797(21)00290-7/fulltext 2021]
**"Alzahrani and colleagues rightly point out that their models test for and thus demonstrate statistically independent effects of smoking and vaping, but if vaping and smoking are not actually independent contributors to identifying MI occurrence—that is, if the association between e-cigarette use and MI occurrence varies as a function of combustible cigarette use—then the main-effects model cannot be used to draw conclusions about the association between e-cigarette use and MI, independent of (or regardless of) one's history of combustible cigarette use." (Critcher, Siegel)
*See also: [https://sci-hub.wf/10.1016/j.amepre.2019.03.012 2019]
**"As the debate on the risks−benefits of electronic-cigarettes continues, a rigorous evidence base is critical. Although determining whether the use of e-cigarettes carries excess risk for future MI is important, it is not possible through the analysis of cross-sectional data, such as the National Health Interview Survey data, from which temporality cannot be inferred. Equally important, we were unable to replicate the authors’ findings. Given the importance of this topic to public health, we request that the authors provide a full and comprehensive explanation for the discrepancies noted and temper their conclusions about “increased risk of myocardial infarction” to reflect the limitations of cross-sectional data." (Bover Manderski, Singh, Delnevo)
* See also: [https://sci-hub.wf/10.1016/j.amepre.2018.06.007 2018]
**"Of concern,however, is the fact that 95% of EC users were also former or current tobacco cigarette (TC) smokers, and the timing of the MI relative to onset of EC use is unknown. (Middlekauff, Gornbein)
*See also: [https://sci-hub.se/10.1016/j.amepre.2018.11.013 2018]
**"Our findings show the well-established limitations of cross-sectional studies, which cannot justify any claims about causal inference, as mentioned in the conclusion by Alzahrani and colleagues.1 Therefore, the conclusion of their study is incorrect and should be revised." (Farsalinos, Niaura)
***Referring to: Alzahrani T, Pena I, Temesgen N, Glantz SA. [http://Association%20Between%20Electronic%20Cigarette%20Use%20and%20Myocardial%20Infarction Association Between Electronic Cigarette Use and Myocardial Infarction]. Am J Prev Med. 2018 Oct;55(4):455-461. doi: 10.1016/j.amepre.2018.05.004. Epub 2018 Aug 22. Erratum in: Am J Prev Med. 2019 Oct;57(4):579-584. PMID: 30166079; PMCID: PMC6208321.

==Cessation==
To learn more about smoking cessation, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]

===2024: Comments RE: [https://www.linkedin.com/posts/jeffrey-l-weiss_publichealth-mondaythoughts-thoughtleadership-activity-7231288859165143042-XOSF?utm_source=combined_share_message&utm_medium=member_desktop Adult Smoking Cessation — United States, 2022]===
*"Concealing important information is not meaningfully different from disseminating falsehoods. Smokers who have been unable or unwilling to quit all use of nicotine with traditional smoking cessation medicines deserve to know that they still have alternatives. It should be unacceptable that the “lead federal agency for comprehensive tobacco prevention and control” would keep potentially life-saving information from them." (Weiss)
***Referring to: VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641. DOI: http://dx.doi.org/10.15585/mmwr.mm7329a1

===2024: Comments RE: [https://pubpeer.com/publications/A21E464F1BA2A64B02D7ABF3A88965 Declines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surge]===
*"However, the authors’ conclusions are based on questionable methodological decisions and flawed analyses. Most notably:
**A. The joinpoint analysis of declining cigarette smoking is incorrectly conducted, in a way that obscures more rapid declines in current cigarette smoking after 2002;
**B. Rather than conducting a standard analysis (i.e., a weighted and adjusted analysis of e-cigarette use and smoking trends), authors instead base their conclusions on tallying states that meet certain ad hoc and stringent criteria for (unadjusted) e-cigarette use and smoking trends; and
**C. Analyses focus on an inappropriately narrow time window that does not fully capture the relevant dynamics. Together these flaws substantially underestimate the degree to which e-cigarettes may have displaced or offset cigarette smoking among youth and young adults.
**Moreover, the conclusion that e-cigarette uptake is independent of the declines in cigarette smoking runs counter to a large and varied body of evidence that e-cigarettes substitute for or displace cigarettes. The authors only discuss two such papers, attempting to undermine their conclusions using some of the same flaws that underlie their own analyses, and neglect to mention the larger body of evidence. Together, this yields an article that could cause readers to hold a distorted view of the available evidence on these important issues." (Selya, Gitchell, Foxon, Sembower, Niaura)
***Referring to: Pierce JP, Luo M, McMenamin SB, et alDeclines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surgeTobacco Control Published Online First: 08 November 2023. [https://tobaccocontrol.bmj.com/content/early/2023/11/08/tc-2022-057907 doi: 10.1136/tc-2022-057907]

===2016-2020: Comments RE: [https://pubpeer.com/publications/E2628F04937D0DBD870E115CB41C8B E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis]===
*Multiple Comments, many linking to more information
**"The most obvious issue is that the result is based on studies that have no bearing on whether e-cigarettes are effective or not. This is because vapers who successfully quit smoking were excluded and only those who failed to do so were retained. The studies were not at fault, they were just not set up to evaluate quit rates in smokers who try and not try vaping. The fault is with misinterpreting their results. The letter in LRM referenced above provides more details." (Hajek)
*[https://www.sciencemediacentre.org/expert-reaction-to-meta-analysis-looking-at-e-cigarette-use-and-smoking-cessation/ Expert Reaction]
**“Publication of this study represents a major failure of the peer review system in this journal.” (West)
**"The current paper represents the latest attempt to bring together the existing literature on e-cigarettes for smoking cessation. While its breadth is to be commended, its conclusions (that e-cigarettes don’t work for smoking cessation) are at best tentative and at worst incorrect. The main reason for this is that attempting to directly compare the results of a body of literature that uses such a wide range of study designs and includes such variable (and often poorly defined) populations and outcomes is difficult, if not impossible. Some of the observational studies included in the review, in particular, suffer from a range of limitations that don’t allow us to reliably assess whether e-cigarettes help smokers quit." (Bauld)
**“Evidence from practice in England shows that two out of three smokers who combined e-cigarettes with additional expert support from a local stop smoking service quit successfully and while dual use is a complex issue, many vapers report using an e-cigarette to cut down and ultimately quit." (O'Connor)
**“This review is grossly misleading in my opinion. There are several problems with the way studies were selected and used, but the main flaw is simple, though not easy to spot. The studies that are presented as showing that vaping does not help people quit only recruited people who were currently smoking and asked them if they used e-cigarettes in the past. This means that people who used e-cigarettes and stopped smoking were excluded. The same approach would show that proven stop-smoking medications do not help or even undermine quitting." (Hajek)
**“This review is not scientific. The information included about two studies that I co-authored is either inaccurate or misleading. In addition, the authors have not included all previous studies they could have done in their meta-analysis. I believe the findings should therefore be dismissed. I am concerned at the huge damage this publication may have – many more smokers may continue smoking and die if they take from this piece of work that all evidence suggests e-cigarettes do not help you quit smoking; that is not the case." (McNeill)
*[https://clivebates.com/who-will-be-duped-by-error-strewn-meta-analysis-of-e-cigarette-studies/ Who will be duped by error-strewn ‘meta-analysis’ of e-cigarette studies?]
**"There are multiple challenges with interpreting the e-cigarette studies routinely appearing in the scientific literature – and over-interpretation is all too easy or even deliberate." (Bates)
*[https://web.archive.org/web/20151026231500/http://truthinitiative.org/sites/default/files/2015.06.30%20E-Cig%20FDA%20Workshop%20Docket%20FINAL.pdf Legacy Foundation (now Truth Initiative) submission to the FDA]
**"While the majority of the studies we reviewed are marred by poor measurement of exposures and unmeasured confounders, many of them have been included in a meta-analysis that claims to show that smokers who use e-cigarettes are less likely to quit smoking compared to those who do not.[73] This meta- analysis simply lumps together the errors of inference from these correlations. As described in detail above, quantitatively synthesizing heterogeneous studies is scientifically inappropriate and the findings of such meta-analyses are therefore invalid."
**"Findings from the studies with the strongest methodologies suggest that e-cigarettes are effective in helping adult smokers to quit or to reduce their cigarette consumption and that rates of smoking cessation with e-cigarettes are similar to rates of cessation with nicotine replacement therapy."
*[https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(16)30024-8.pdf Correspondence]
**"There are other problems—such as selective inclusion of studies, and selective reporting of data from studies that were included —and limitations the authors acknowledge in the text but ignore in their conclusions. Detailed criticism of the methods is, however, not needed, because lumping incongruous studies together—which were mostly not designed to evaluate the efficacy of e-cigarettes, and contain no useful information on this topic unless misinterpreted—makes no scientific sense in the first place." (Hajek, McRobbie, Bullen)
*[https://antithrlies.com/2016/01/17/sunday-science-lesson-what-is-meta-analysis-and-why-was-glantzs-inherently-junk/ Sunday Science Lesson: What is “meta-analysis”? (and why was Glantz’s inherently junk?)]
**"Glantz’s meta-analysis is not just junk science because of details about the studies, though those are problems in themselves. It is junk science because there are probably not even two of the studies in his collection that are similar enough to average together, let alone all of them." (Phillips)
***Referring to: Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016 Feb;4(2):116-28. [https://pubmed.ncbi.nlm.nih.gov/26776875/ doi: 10.1016/S2213-2600(15)00521-4]. Epub 2016 Jan 14. PMID: 26776875; PMCID: PMC4752870.

==COVID==

===2022: Comments RE: [https://pubpeer.com/publications/362B01D2B4E5398302F22585990F19#1 Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review]===
*"It is important to state that there is no empiric evidence of transmission of the SARS-CoV-2 virus or any other pathogen through vaping expirations. None of the sources cited by the authors on this issue (references cited in the first paragraph above) provide such evidence, they merely speculate about it in very vague general terms.
*Given the lack of experimental detection, the potential plausibility and scope of this pathogen transmission should be discussed through well structured models based on the theory and data of pathogen transmission mechanisms. Unfortunately, the authors missed three extensive articles in which we undertook this task (links to the articles). (Sussman)
**Referring to: Singhal S, Degano C, Berenbaum E, Keller-Olaman S. Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review. [https://pubmed.ncbi.nlm.nih.gov/35881057/ J Can Dent Assoc. 2022 Jan;88:m1]. PMID: 35881057.

===2020: Comments RE: [https://pubpeer.com/publications/CEB008BBD48F89272321EB50092793 Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19]===
*Multiple Comments:
**"This article is getting severe criticism on Twitter. This thread summarises one issue and links to threads on other, more classic, problems." (Brown) Further comments by the same author (Brown) point out some errors in tables.
**"The authors surveyed and controlled for socioeconomic factors, ethnicity and compliance with confinement precautions, but not for other risk behaviors besides smoking or vaping (such as alcohol drinking, substance usage, unprotected sex). The lack of this important comparative context further weakens the conclusions of this study." (Sussman)
**"Flaws in the paper itself are only one part of the problem that needs to be addressed by the authors. The other is the public relations offensive mounted on the back of the paper once it was published in the Journal of Adolescent Health on August 11." "Unsurprisingly, such an incendiary claim generated considerable media coverage, even though there is no basis for it in fact or evidence." "Finally, there was a political dimension. On the same day as the article was published, August 11, 2020, Illinois Congressman Raja Krishnamoorthi, Chairman of the Subcommittee on Economic and Consumer Policy, found time to write a press release and letter to the Commissioner of the Food and Drug Administration, Dr. Stephen Hahn demanding FDA "clear the market of e-cigarettes" in response to the study." (Bates)
*See Also:[https://www.qeios.com/read/A58MQC Qeios 1]
**"In this brief peer review, we argue that the data reported by Gaiha et al (https://doi.org/10.1016/j.jadohealth.2020.07.002) regarding associations between vaping and COVID-19 testing are so suspect that any conclusions drawn from it cannot be relied upon. We discuss six main areas of concern and conclude that the paper should be retracted." (Gitchell, Kleykamp, Niaura, Shiffman, Cummings, Sweanor, Abrams)
*[https://www.qeios.com/read/TCEJ7G Qeios 2]
**"In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study." (Farsalinos, Niaura)
***Referring to: Gaiha SM, Cheng J, Halpern-Felsher B. Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19. J Adolesc Health. 2020 Oct;67(4):519-523. [https://www.jahonline.org/article/S1054-139X(20)30399-2/fulltext doi: 10.1016/j.jadohealth.2020.07.002]. Epub 2020 Aug 11. PMID: 32798097; PMCID: PMC7417895.

==Diabetes and Prediabetes==

===2022: Comments RE: [https://pubpeer.com/publications/D3C8E2035BE5C164E9BC19D8D50571 E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey]===
*"The results by Atuegwu et al. are deficient and unreliable, because the authors used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease." (Rodu)
**Referring to: Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM. E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey. Drug Alcohol Depend. 2019 Dec 1;205:107692. [https://pubmed.ncbi.nlm.nih.gov/31707269/ doi: 10.1016/j.drugalcdep.2019.107692]. Epub 2019 Oct 28. PMID: 31707269; PMCID: PMC6893144.

===2022: Comments RE: [https://pubpeer.com/publications/3638F392BE76DCA7CA57ABC8E554BF#1 The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018]===
*"The study by Zhang et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Their results are deficient and unreliable, because a recent analysis by my research group provides definitive evidence that the vast majority of diseases reported by vapers in cross-sectional surveys had been diagnosed before survey participants initiated the behavior." (Rodu)
*2022 Article: [https://www.acsh.org/news/2022/03/08/ignore-headlines-theres-no-science-linking-vaping-prediabetes-16172 Ignore The Headlines: There's No Science Linking Vaping To Prediabetes] (English)
**Limitations of this study include self-report of tobacco use and lack of medical confirmation of prediabetes and other diet information
**BRFSS is a cross-sectional survey, so a causal relationship between E-cigarette use and prediabetes cannot be inferred.
***Referring to: Zhang Z, Jiao Z, Blaha MJ, Osei A, Sidhaye V, Ramanathan M Jr, Biswal S. The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018. Am J Prev Med. 2022 Jun;62(6):872-877. [https://www.ajpmonline.org/article/S0749-3797(22)00024-1/fulltext doi: 10.1016/j.amepre.2021.12.009]. Epub 2022 Mar 3. PMID: 35597566.

==EVALI==

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
**Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Flavors==
*For more information about flavors, please see our page: [https://safernicotine.wiki/mediawiki/index.php/ENDS_Flavors ENDS Flavors]

===2022: [https://pubpeer.com/publications/62DEA1F7805686A6D0172A6B69EFFA Levels of menthol, nicotine and cooling agents measured in JUUL products purchased across a three-year period]===
*The implications made about JUUL products in this study are contradicted by our own contemporaneous and detailed product and manufacturing records and are more readily explained by a methodological artifact that the authors have not fully reported, even after a direct prompt before submitting the manuscript. (Gillman)
**[https://tobaccocontrol.bmj.com/content/33/2/e1 Correction to original paper]
*The PubPeer entry from Juul Labs Inc. (JLI) raises a number of serious questions about this research, the research conduct of the authors, and the editorial practices of the journal. (Bates)
*Referring To: Yassine A, El Hage R, El-Hellani A, et al. Levels of menthol, nicotine, and cooling agents measured in JUUL products purchased across a three-year period Tobacco Control 2022;31:s234-s237. [https://doi.org/10.1136/tc-2022-057506 https://doi.org/10.1136/tc-2022-057506]

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
*Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Gateway==
*To learn more about Gateway, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_are_a_gateway_to_smoking Myth: Alternative nicotine products are a gateway to smoking]

===2024: Comments RE: [https://pubpeer.com/publications/EAD2B506813B485178822E76F2377F Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey]===
*"Causation vs. association. While the authors are careful in most places to avoid claiming that this association is causal, the authors seem to ultimately conclude in favor of a (causal) gateway hypothesis, which is inappropriate given unmeasured confounding by other “common liability” factors, and the cross-sectional nature of the data." (Selya)
*Referring to: Li S, Zeng X, Di X, Liu S. Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey. Front Public Health. 2024 Jan 15;11:1272680. PMID: 38288432; PMCID: PMC10823011 [https://pubmed.ncbi.nlm.nih.gov/38288432/ doi: 10.3389/fpubh.2023.1272680]

===2022: Comments RE: [https://pubpeer.com/publications/9F3E9313EAE06ED991EE4834D69C8E Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study]===
*"The present re-analysis shows that the report of a gateway effect in the NYTS data by Harrell et al. is not supported by these data when appropriate statistical methodology is applied." (Foxon)
*Referring to: Harrell MB, Mantey DS, Chen B, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Prev Med. 2022 Nov;164:107265. Epub 2022 Sep 22. PMID: 36152819; PMCID: PMC10381788. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381788/ doi: 10.1016/j.ypmed.2022.107265]

===2021: Comments RE: [https://www-sciencemediacenter-de.translate.goog/alle-angebote/research-in-context/details/news/e-zigaretten-als-einstieg-zum-zigarettenrauchen/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en-US Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking]===
*Statements:
*; Prof. Dr. Ute Mons, Head of the Cardiovascular Epidemiology of Aging Working Group, Clinic III for Internal Medicine, Cologne University Hospital : “Since there was no statistical control for possible disruptive factors, a causal interpretation, as it is heard between the lines by the authors, is not justified. It should also be taken into account that the study period ran from 2013 to 2017, but the sale of e-cigarettes to young people in the USA was not banned until 2016.For a long time, e-cigarettes were simply more readily available to young people than conventional cigarettes."
*; Prof. Dr. Daniel Kotz, Professor of Addiction Research and Clinical Epidemiology, Institute for General Practice, University Hospital Düsseldorf : “Overall, there is no clear scientific evidence that e-cigarettes are an entry point into tobacco consumption for adolescents and young adults. It is more likely that a personal basic inclination towards nicotine products and the social environment influence the consumption of e-cigarettes or tobacco independently of one another (so-called common liability theory). International studies show that tobacco smoking is falling among adolescents, even in countries where the consumption of e-cigarettes has increased [2]. This contradicts the so-called gateway theory."
*;Prof. Dr. Heino Stöver, Managing Director of the Institute for Addiction Research Frankfurt (ISFF), Frankfurt University of Applied Sciences : “The study is not suitable for making valid statements about e-cigarettes. The main weak point of the study is that it does not take into account the motives for smoking. According to the current state of research, there is no significant causal relationship between the use of e-cigarettes and subsequent smoking. The research situation points in the opposite direction: The majority of adolescents use e-cigarettes no more than experimenting or occasionally using them. In the future, a research design is required that not only examines correlation but also real causality. Unfortunately, this is still not the case. Not even in this study. Such shortcomings underestimate the great and positive role of the e-cigarette in smoking cessation.With 95 percent fewer pollutants than conventional cigarettes, they are well suited for smokers who want to get rid of their addiction and minimize their risk."
*Refering to: John P. Pierce, Ruifeng Chen, Eric C. Leas, Martha M. White, Sheila Kealey, Matthew D. Stone, Tarik Benmarhnia, Dennis R. Trinidad, David R. Strong, Karen Messer; Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking. Pediatrics February 2021; 147 (2): e2020025122. [https://publications.aap.org/pediatrics/article/147/2/e2020025122/36274/Use-of-E-cigarettes-and-Other-Tobacco-Products-and?autologincheck=redirected 10.1542/peds.2020-025122]

===2018: Comments RE: [https://rodutobaccotruth.blogspot.com/2018/01/tobacco-gateway-report-omits-important.html Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015]===
*The Chaffee article emphasizes odds ratios but omits or obscures important contextual information. While teens who try one tobacco product are more likely to try another, the dominant gateway in the PATH survey was from no previous tobacco use to cigarettes. (Rodu)
*Referring to: Watkins SL, Glantz SA, Chaffee BW. Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015. JAMA Pediatr. 2018;172(2):181–187. [http://doi:10.1001/jamapediatrics.2017.4173 doi:10.1001/jamapediatrics.2017.4173]

===2016: Comments RE: [http://tobaccoanalysis.blogspot.com/2016/06/new-pediatrics-study-provides.html E-Cigarettes and Future Cigarette Use] (#1)===
*The study counted anyone who had even puffed a cigarette once as being a smoker. So theoretically, a subject could have had a single puff of an e-cigarette and hated it, and then had a single puff of a cigarette and hated it, and they would be considered someone who initiated smoking because of vaping first. (Siegel)
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-e-cigarettes-and-future-cigarette-use/ E-Cigarettes and Future Cigarette Use] (#2)===
*Prof. Ann McNeill, Professor of Tobacco Addiction at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London : “The gateway hypothesis in the addictions field is frequently used but is highly contested as it has a poor evidence base in general. This study does nothing to strengthen that evidence base.”
*Prof. Peter Hajek, Director of the Tobacco Dependence Research Unit at Queen Mary University of London : "Like several previous studies of this type, this one just shows that people who try things, try things."
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://tobaccoanalysis.blogspot.com/2016/08/new-study-purports-to-show-that-e-cigs.html E-cigarette use is differentially related to smoking onset among lower risk adolescents ]===
*"To be clear, the rest of the story is that this new study provides no evidence that e-cigarettes are a gateway to smoking. Instead, it confirms that actual drug-related risk-taking behavior is a much better predictor of other drug-related risk-taking behavior than simply asking a kid if he thinks he will try another drug in the future or asking a kid how rebellious he is or how much his parents support him."
*"This second problem is that smoking initiation was measured by any experimentation with cigarettes, even if just a puff. So many of the youth in the sample may have puffed on a single e-cigarette at baseline and then puffed on a single cigarette some time over the next year and that would be considered as providing evidence that e-cigarettes are a "gateway" to smoking." (Siegel)
*Referring to: Wills TA, Sargent JD, Gibbons FX, et al E-cigarette use is differentially related to smoking onset among lower risk adolescents [https://tobaccocontrol.bmj.com/content/26/5/534 Tobacco Control 2017;26:534-539].

===2026: Comments RE: Flavored Electronic Cigarette Use and Smoking Among Youth===
*"The problems are obvious to those with any experience in statistics; the paper suffers from recall bias, sampling bias, and drawing causal conclusions from a cross-sectional survey. One of those confounders would be troubling yet the paper contains all of them." ([https://www.acsh.org/news/2016/11/07/all-animals-arent-cows-all-tobacco-isnt-cigarettes-and-surveys-arent-science-10412 Campbell])
*"This is a great example of the widespread bias against e-cigarettes that has taken hold in the tobacco control movement. Instead of presenting the study as showing equivocal results, the investigators and the American Academy of Pediatrics have both "chosen sides." This is not science; it is biased interpretation and presentation of science." ([https://tobaccoanalysis.blogspot.com/2016/11/investigators-botch-interpretation-of.html Siegel])
*Referring to: Hongying Dai, Jianqiang Hao; Flavored Electronic Cigarette Use and Smoking Among Youth. Pediatrics December 2016; 138 (6): e20162513. 10.1542/peds.2016-2513

===2014: Comments RE: [https://tobaccoanalysis.blogspot.com/2014/08/politicians-lie-to-public-about.html Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study]===
*"In a press release issued Monday by 13 members of Congress, a group of politicians claimed that there is "more" evidence that electronic cigarettes are a gateway to smoking...The reference which supports this assertion is a study by Dutra and Glantz which purports to provide data showing that electronic cigarettes are aggravating the tobacco epidemic among youth...The authors of this study make one of the most cardinal errors in all of epidemiology. They ignore the principle that correlation does not equal causation." (Siegel)
*Referring to: Dutra LM, Glantz SA. Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study. JAMA Pediatr. 2014 Jul;168(7):610-7. [http://doi:%2010.1001/jamapediatrics.2013.5488 doi: 10.1001/jamapediatrics.2013.5488]. Erratum in: JAMA Pediatr. 2014 Jul;168(7):684. PMID: 24604023; PMCID: PMC4142115.

==HPHC - Harmful and Potentially Harmful Constituents==

===2024: Comments RE: [https://www.pubpeer.com/publications/2D5B14D827614B6D4EFC821DCD2715 In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting]===
*"As a summary: the study by Beard et al [1] was conducted under such unrealistic conditions that its results (including its cytotoxic analysis) have little relevance to consumers and regulators." (Soulet, Sussman)
*Referring to: Beard JM, Collom C, Liu JY, Obiako P, Strongin RM, Zavala J, Sayes CM. In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting. Toxicology. 2024 Jun 13;506:153865. doi: 10.1016/j.tox.2024.153865. Epub ahead of print. PMID: 38876198.

===2024: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-observational-study-of-lead-and-uranium-levels-in-urine-of-teen-vapers/ Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring]===
*"More important, to me as a statistician at least, is that this research can’t establish that the higher levels of lead and uranium in the urine of participants who said they vaped more often were actually caused by their vaping." (McConway)
*"No control group (i.e., adolescents without any e-cigarette use) was included in the analysis...This study therefore cannot tell us anything about absolute increase in exposure to heavy metals from e-cigarette use in this population, only about relative exposure among less and more frequent e-cigarette users." (Shahab)
*See Also: [https://pubpeer.com/publications/E1834A07BDF105C94CC44DD0815856 PubPeer] "The reported mean values are then consistently far below the limit of detection. To draw any conclusions from values below LOD, is bad practice at best."
*Referring to: Kochvar A, Hao G, Dai HD Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring Tobacco Control Published Online First: 29 April 2024. doi: 10.1136/tc-2023-058554

===2023: Comments RE: [https://pubpeer.com/publications/F7311DC3982D9CD03C060190C9CFCB Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study]===
*The article has several serious shortcomings
**REPRODUCIBILITY AND LACK OF CRUCIAL INFORMATION.
**INAPPROPRIATE AIRFLOW FOR SUB-OHM DEVICES.
**ERRONEOUS CONCENTRATION VALUES
**STORAGE (Sussman)
*Referring to: Tehrani MW, Ahererra AD, Tanda S, Chen R, Borole A, Goessler W, Rule AM. Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study. Journal of Environmental Exposure Assessment. 2023; 2(2): 9. http://dx.doi.org/10.20517/jeea.2023.03

===2022: Comments RE: [https://pubpeer.com/publications/C4BE0346C79DAAC7E1BB2DD6B6FAA3#1 Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence]===
*The reader may find the following commentary on Uguna & Snape by Chris Snowdon of interest. It includes a scientific review of the paper by Roberto Sussman that provides a convincing rebuttal of the author's assertions that heated tobacco products generate smoke. (Bates)
*Referring to: Uguna CN, Snape CE. Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence. ACS Omega. 2022 Jun 22;7(26):22111-22124. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260752/ doi: 10.1021/acsomega.2c01527]. PMID: 35811880; PMCID: PMC9260752.

===2022: Comments RE: [https://pubpeer.com/publications/CF1D17EA015361EED28A7886C21CC1#1 Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors]===
*"Conclusion. This study might be a correct and rigorous examination of various processes of the particulate phase of e-cigarette aerosol that are strictly valid under the abnormal overheating testing conditions. The study does not prove that such processes can occur in low powered devices, or even in high powered devices under the recommended power ranges and airflow rates normally used by consumers. The utility to assess the safety profile of e-cigarettes requires the devices to be tested under the best approximation possible to realistic usage. Unfortunately, this study failed to comply with this important consistency condition." (Sussman)
*Referring to: Dada O, Castillo K, Hogan M, Chalbot MG, Kavouras IG. Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors. Sci Rep. 2022 Nov 3;12(1):18571. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633786/ doi: 10.1038/s41598-022-21798-w]. PMID: 36329089; PMCID: PMC9633786.

===2017: Comments RE: [https://pubpeer.com/publications/6E2711F55673ADF831D636E2D701B9 "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions]===
*Multiple Comments
**"Users will operate the equipment in a way that does not lead to harsh dry puff conditions, with associated high VA formation. This is a key human control feedback that does not exist in laboratory equipment. So experiments that just standardise power settings or volume consumption must take care to validate these are realistic proxies for human use for a particular device. In this paper, many of the coil, power and volume settings combinations were not realistic. That could have been avoided through engaging with people with real practical expertise." (Bates)
**"In reality, as power to the coil increases, liquid consumption also increases. In real-world scenarios, human users regulate both power and liquid flow to minimise the risk of dry-puff conditions and therefore avoiding increases in VA emissions." (Barnes)
*Referring to: Soha Talih, Rola Salman, Nareg Karaoghlanian, Ahmad El-Hellani, Najat Saliba, Thomas Eissenberg, and Alan Shihadeh Chemical Research in Toxicology 2017 30 (10), 1791-1793 [https://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00212 DOI: 10.1021/acs.chemrestox.7b00212]

===2017: Comments RE: [https://pubpeer.com/publications/E5B66481CC847E532FEDB066434E92 Hidden formaldehyde in e-cigarette aerosols]===
*"The problem for the authors is that cancer is a human condition and their calculation is based exposures measured by a lab machine in conditions that no humans would be able to tolerate." (Bates)
*See also: [https://pubpeer.com/publications/5D8FB0EB72850380D1A37DAA2097D6 PubPeer 2015-2017]
**"Although Jensen et al. mentioned in the 2015 NEJM research letter that the health risks of formaldehyde hemiacetal inhalation are unknown ("How formaldehyde-releasing agents behave in the respiratory tract is unknown..."), they made a calculation that the formaldehyde-attributable cancer risk from e-cigarette use is 5 to 15 times higher than from long-term smoking. These two statements are clearly contradictory, and the calculation of any cancer risk from formaldehyde hemiacetal emissions is invalid since no such risk has been established for these compounds." (Farsalinos)
*See also: [https://pubmed.ncbi.nlm.nih.gov/28864295/ replication study]
**"The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided." (Farsalinos, Voudris, Spyrou, Poulas)
*See also 2015: [https://retractionwatch.com/2015/09/11/researchers-call-for-retraction-of-nejm-paper-showing-dangers-of-e-cigarettes/ Researchers call for retraction of NEJM paper showing dangers of e-cigarettes]
**Links to the efforts to have the referenced paper retracted.
*Referring to: Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. [https://www.nejm.org/doi/full/10.1056/nejmc1413069 doi: 10.1056/NEJMc1413069]. PMID: 25607446.

==Marketing / Social Media==

===2019: Comments RE: [https://www.juullabs.com/study-highlights-influence-of-illegal-compatible-products/ Characterising JUUL-related posts on Instagram]===
*A recent study in Tobacco Control relating to an analysis of “JUUL-related” Instagram posts contains serious factual errors and mischaracterizations of JUUL Labs’ historical social-media activity, falsely tying the company to the activities of manufacturers of “JUUL compatible” products that we believe are illegally on the market. (JUUL)
* [https://pubpeer.com/publications/B1DD80F0C868A59D609F0B9699E5F9 Additional comments]: In fact, a completely different story emerges from the data as qualified by Juul's statement. This is that FDA's failure to control newly-introduced Juul look-a-likes (which are illegal if introduced after 8 August 2016) is spawning a lawless industry driven by social media and in conflict with Juul's efforts to control sales of its products to youth. The study does not interrogate the underlying reality and I think Juul is right to react strongly. (Bates)
**Referring to: Czaplicki L, Kostygina G, Kim Y, Perks SN, Szczypka G, Emery SL, Vallone D, Hair EC. Characterising JUUL-related posts on Instagram. Tob Control. 2020 Nov;29(6):612-617. Epub 2019 Jul 2. PMID: 31266903. [https://doi.org/10.1136/tobaccocontrol-2018-054824 doi: 10.1136/tobaccocontrol-2018-054824]

==Multiple Outcomes==

===2024: Comments RE: [https://www.ecigarette-research.org/research/index.php/research/2024/281-ecig-disease Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===
*"The study provides zero evidence on any risk associated with e-cigarette use, whether absolute risk or in comparison with smoking. The question that was supposed to be addressed in this metanalysis CANNOT be examined with the studies included in their analysis." (Farsalinos)
*[https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 See Also]: "The methods look impressive, but the devil is in the dirty details buried in the nearly 100 pages supplemental material. The authors have done an admirable job collecting studies and organizing them, but the conclusions reached are untenable, and unsupportable at least for now." (Cummings)
**Referring to: Glantz SA, Nguyen N, Oliveira da Silva AL. Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes. NEJM Evid. 2024 Mar;3(3):EVIDoa2300229. Epub 2024 Feb 27. PMID: 38411454. [https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300229 doi: 10.1056/EVIDoa2300229]

===2024: Comments RE: [https://tobaccocontrol.bmj.com/content/33/3/373.responses#-comments-on-paper-by-asfar-et-al-%E2%80%9Crisk-and-safety-profile-of-electronic-nicotine-delivery-systems-ends-an-umbrella-review-to-inform-ends-health-communication-strategies%E2%80%9D Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies]===
*"Communicating health risk information about ENDS has to have some context to be meaningful to consumers. A common misconception about tobacco use is that the most dangerous component of the product is nicotine. However, while nicotine can be addictive, it is the other toxicants in tobacco, especially burned tobacco, that are the true culprits of tobacco-related diseases. Thus, when communicating information about the health risks of tobacco products, it makes sense to provide consumers with information about the relative health dangers from burned compared to unburned tobacco products. The example risk messages included in the supplementary materials to the paper appear to be developed with a goal of discouraging anyone from using a vaping product rather than to inform potential users about risks." (Cummings, Smith, Schroeder, Warner, McNeill, Hartmann-Boyce, Levy)
**Referring to: Asfar T, Jebai R, Li W, Oluwole OJ, Ferdous T, Gautam P, Schmidt M, Noar SM, Lindblom EN, Eissenberg T, Bursac Z, Vallone D, Maziak W. Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies. Tob Control. 2022 Sep 8:tobaccocontrol-2022-057495. doi: [https://tobaccocontrol.bmj.com/content/33/3/373 10.1136/tc-2022-057495]. Epub ahead of print. PMID: 36252567; PMCID: PMC10043882.

===2022: Comments RE: [https://colinmendelsohn.com.au/wp-content/uploads/2022/07/Mendelsohn-Wodak-Hall-Borland.-A-critical-analysis-of-Ecigs-and-health-outcomes-systematic-review-of-global-evidence.-DAR-2022.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]===
*Contrary to the conclusions of the Banks review, the evidence suggests that vaping nicotine is an effective smoking cessation aid; that vaping is substantially less harmful than smoking tobacco; that vaping is diverting young people away from smoking; and that vaping by smokers is likely to have a major net public health benefit if widely available to adult Australian smokers. (Mendelsohn)
**Referring to: Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. [https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022.

===2022: Comments RE: [https://pubpeer.com/publications/727EA7B64FB27270F20717729D7629 Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice]===
*Although this new research from Moshensky et al., does add to the scientific literature about previously marketed JUUL products, we believe the conclusions presented in the manuscript are not adequately supported by the study data. In addition, the lack of quantitative data on actual dosing limits the ability to establish relevance to potential human exposures from product use. Furthermore, the lack of a comparison against the effects of tobacco smoke limits the ability to evaluate these study findings in the context of the tobacco product risk continuum, and risk relative to use of combusted cigarettes. (Weil)
**Referring to: Moshensky A, Brand CS, Alhaddad H, Shin J, Masso-Silva JA, Advani I, Gunge D, Sharma A, Mehta S, Jahan A, Nilaad S, Olay J, Gu W, Simonson T, Almarghalani D, Pham J, Perera S, Park K, Al-Kolla R, Moon H, Das S, Byun MK, Shah Z, Sari Y, Heller Brown J, Crotty Alexander LE. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife. 2022 Apr 12;11:e67621. PMID: 35411847; PMCID: PMC9005188. [https://doi.org/10.7554/elife.67621 doi: 10.7554/eLife.67621]

===2018: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-modelling-study-on-electronic-cigarettes-in-the-us/ Quantifying population-level health benefits and harms of e-cigarette use in the United States]===
*"The authors make some very speculative assumptions here, particularly on the ‘gateway’ effect in teenagers – they assume that vaping leads to smoking. The trouble is, all their data on this comes from studies that don’t prove anything of the sort...The authors’ estimate of ‘life years lost’ is primarily driven by their overestimate of e-cig use contributing to a significant increase in the uptake of smoking in kids." (Shahab)
*"This new ‘finding’ is based on the bizarre assumption that for every one smoker who uses e-cigs to quit, 80 non-smokers will try e-cigs and take up smoking. It flies in the face of available evidence but it is also mathematically impossible." (Hajek)
**Referring to: Soneji SS, Sung HY, Primack BA, Pierce JP, Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS One. 2018 Mar 14;13(3):e0193328. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193328 doi: 10.1371/journal.pone.0193328]. PMID: 29538396; PMCID: PMC5851558.

==Respiratory==
*To learn more about Popcorn Lung, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Vaping_causes_Popcorn_Lung Myth: Vaping causes Popcorn Lung]

===2023: Comments RE: [https://pubpeer.com/publications/035039E269389CBFC88FCB9AFD225C#8 E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring]===
*Given all these shortcomings (opaqueness, unrealistic airflow and nicotine, likely overexposure of mice), the results of this study are not reliable to assess potential harms from exposure to e-cigarette aerosol. (Sussman)
*Referring to: Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, Miller RA, Wold LE, Gorr MW. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L676-L682. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722245/ doi: 10.1152/ajplung.00233.2022]. Epub 2022 Oct 11. PMID: 36218276; PMCID: PMC9722245.

===2022: Comments RE: [https://pubpeer.com/publications/D93498039BF8D05DFAE58BFC29DD1B The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Therefore, it is deficient and unreliable." (Rodu)
*Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019 Oct 16;19(1):180. [https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0950-3 doi: 10.1186/s12890-019-0950-3]. PMID: 31619218; PMCID: PMC6796489.

===2022: Comments RE: [https://pubpeer.com/publications/075B90E6B4FEB1AF3BB188690C317F Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017]===
*"The study by Osei et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Osei, A. D., Mirbolouk, M., Orimoloye, O. A., Dzaye, O., Uddin, S. M. I., Benjamin, E. J., Hall, M.E., DeFilippis, A.P., Bhatnagar, A., Biswal, S.S., Blaha, M. J. (2020). Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017. American Journal of Preventive Medicine. [https://www.ajpmonline.org/article/S0749-3797(19)30479-9/fulltext https://doi.org/10.1016/j.amepre.2019.10.014]

===2022: Comments RE: [https://pubpeer.com/publications/8993443E1BA20DF0D8F4E1F51DFB79 Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data]===
*"The study by Wills et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Wills TA, Choi K, Pokhrel P, Pagano I. Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data. Prev Med. 2022 Aug;161:107137. [https://www.sciencedirect.com/science/article/abs/pii/S0091743522001864 doi: 10.1016/j.ypmed.2022.107137]. Epub 2022 Jul 9. PMID: 35820496; PMCID: PMC9328844.

===2022: Comments RE: [https://pubpeer.com/publications/7B80EB6A718B6A0F2B4634DFE56886 E-cigarette use and respiratory disorder in an adult sample]===
*"Their study used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
*Referring to: Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019 Jan 1;194:363-370. [https://www.sciencedirect.com/science/article/abs/pii/S0376871618307622 doi: 10.1016/j.drugalcdep.2018.10.004]. Epub 2018 Nov 7. PMID: 30472577; PMCID: PMC6312492.

===2022: Comments RE: [https://pubpeer.com/publications/9946B2A97F6F6AF0F898D95F7CB23D E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report]===
*"The problem with these studies is disentangling the effects of a smoking career (something more complicated than adjusting for current-, former-, never-smoking status) and subsequent vaping behaviour. Also, the relationships are complicated by reverse causation (was the vaping a response to smoking-induced respiratory symptoms?), a hard-to-define counterfactual (has the vaping displaced smoking or displaced abstinence?), and the fact that respiratory damage arises from cumulative exposure and vaping exposures may be adding incremental risk (would the subject have any symptoms if they hadn't smoked first?)." (Bates)
*Referring to: Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 Dec 1;17(12):e0269760. [https://pubmed.ncbi.nlm.nih.gov/36454742/ doi: 10.1371/journal.pone.0269760]. PMID: 36454742; PMCID: PMC9714717.

===2020: Comments RE: [https://pubpeer.com/publications/EF05B531214379DD314797A20F2D9D Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?]===
*"The problem is that vegetable glycerin (glycerol) is not a lipid it is an alcohol. It cannot cause the lipoid pneumonia symptoms mentioned." (Bates)
*"Endogenous lipoid pneumonia from VG (or PG) inhalation is a speculation and implausible...The experience in the US over the past several months clearly shows that the culprit for the acute lung intoxication cases are black market THC oils which were sold as THC oils, not e-cigarette products." (Farsalinos)
*"visual assessment of lung HRCT scans showed no pathological findings in people vaping daily for more than 3.5 years. In particular, no CT features compatible with early signs of COPD (i.e. parenchymal micronodules, ground-glass opacity, or macroscopic emphysema) or lipoid pneumonia or popcorn lung disease were present." (Polosa)
*Referring to: Eissenberg T, Maziak W. Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury? Am J Respir Crit Care Med. 2020 Apr 15;201(8):1012-1013. [https://pubmed.ncbi.nlm.nih.gov/31917600/ doi: 10.1164/rccm.201910-2082LE]. PMID: 31917600; PMCID: PMC7159422.

===2019-2020: Comments RE: [https://pubpeer.com/publications/7571819CEB7A2BC425BE3D7061410D Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis]===
*Multiple Comments:
**"One of the essential criteria of causal inference is that exposure to the cause precedes disease onset. Three of the diseases Glantz studies — COPD, chronic bronchitis and emphysema — take decades to become clinically apparent and would have been present, even though undiagnosed, in many of his cases long before his study began in 2014, and indeed even before e-cigarettes first became available in the US in about 2007. His findings are also flawed by the fact that most vapers have smoked, and since smoking is a strong cause of chronic lung disease, vapers inevitably carry an increased risk of lung disease long after quitting smoking. Glantz claims to have allowed for this statistically but his approach is simplistic: he lacks the detail of lifetime duration and intensity of smoking required. On these grounds alone his conclusion is specious." (Britton)
**"Donald Kenkel and colleagues at Cornell University conducted a replication of the analysis using econometric techniques...When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco." (Bates)
*Referring to: Bhatta DN, Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020 Feb;58(2):182-190. [https://www.ajpmonline.org/article/S0749-3797(19)30391-5/fulltext doi: 10.1016/j.amepre.2019.07.028]. Epub 2019 Dec 16. PMID: 31859175; PMCID: PMC6981012.

===2019: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-ecig-vapour-and-cancer-in-mice/ Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice]===
*Multiple comments:
**“The comparison between mice breathing vapour and mice breathing air is not statistically significant. There is no sample size justification and no power calculation. There is no message to the public here – I suspect these results are just noise.” (Britton)
**“The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures. The authors assigned the effects they observed to a carcinogen NNK – but NNK has been measured before in human vapers, and it is known that exposure from vaping is either negligible or none.” (Hajek)
*Referring to: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. [https://pubmed.ncbi.nlm.nih.gov/31591243/ doi: 10.1073/pnas.1911321116]. Epub 2019 Oct 7. Erratum in: Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22884. PMID: 31591243; PMCID: PMC6815158.

===2017: Comments RE: [https://pubpeer.com/publications/41F6EA57D0803EEE9DF65162DF0097 Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts]===
*"It is literally true that they "find no evidence...", but that is because this study is completely ill-suited to drawing any policy conclusions about e-cigarettes and COPD. Despite hinting at the limitations of cross-sectional data, the authors draw a negative-sounding conclusion without addressing the key question of how respiratory health changes for a given smoker who uses e-cigarettes to quit or cut down once they are ill from smoking or as a way of preventing COPD." (Bates)
*Referring to: Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. [https://pubmed.ncbi.nlm.nih.gov/28884423/ doi: 10.1007/s11606-017-4150-7]. Epub 2017 Sep 7. PMID: 28884423; PMCID: PMC5698219.

===2016: "Popcorn Lung" Comments RE: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892932/ Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes”]===
**"Over the past five years, we have published the results of several studies in which diacetyl and 2,3-pentanedione levels were measured in various consumer products..."
**"..."hundreds of consumer products (e.g., tea, coffee, citrus juices, butter) contain naturally occurring diacetyl and 2,3-pentanedione...several studies have shown that airborne diketones associated with these products are easily detectable..."
**"Unless one assumes that unflavored coffee beans pose a serious risk of “popcorn lung,” a rare and oftentimes lethal disease, then one should agree that exposures to airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk."
**"Similarly, we measured concentrations of naturally occurring diacetyl and 2,3-pentanedione in mainstream cigarette smoke at levels (200–400 ppm and 30–50 ppm, respectively) that are hundreds of thousands of times higher than the NIOSH and ACGIH OELs, yet cigarette smoking is not associated with “popcorn lung”. Also, as others have noted, diketone exposures from traditional cigarettes are higher than those associated with e-cigarette use, hence switching from tobacco to e-cigarettes may result in reduced diketone exposure."
**"Ironically, suggesting that diketone levels in e-cigarettes are potentially dangerous could actually lead to higher diketone exposures in the smoking population if smokers decide not to switch to e-cigarettes due to as yet unfounded health concerns." (Pierce, Abelmann, Finley) For further information, see authors [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892901/ response] to the comments above.
*See Also: 2016: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892907/ On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings]
**"The 51 e-juices sampled make up a very small proportion of all the products sold, and there is variability in the chemical content of specific products as well as how those chemicals are delivered by different devices. The authors therefore acknowledge that it is impossible to extrapolate their results to all the other products on the market. Importantly, this study did not assess levels of diacetyl, 2,3-pentanedione, and acetoin in actual users, much less health effects. So it’s premature to assume that exposure to these chemicals via e-cigarettes causes health problems." (Arnold)
*See Also: 2015: [https://rodutobaccotruth.blogspot.com/2015/12/is-harvard-e-cigarette-buttery-flavor.html Is the Harvard E-Cigarette Buttery Flavor Study Credible?]
**"As I advised previously, vapers should only use liquids that are certified to be free of buttery flavors that are suspected respiratory toxicants. However, laboratory investigations of e-cigarettes should use validated methods to assure credibility. The results of the Harvard Buttery Flavor Study do not meet this standard." (Rodu)
*See Also: 2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/236-da2 A new study finds diacetyl in e-cigarettes but exaggerates risks and fails to discuss about smoking]
**"In conclusion, the article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes. They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk." (Farsalinos)
*See Also: 2015: [https://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking]
**"Nevertheless, it is disingenuous and actually damaging to the public's health to spread the message that vaping causes fatal lung disease or even that it appears to increase the risk for popcorn lung. And it is especially disingenuous and damaging to send these messages to the public without telling us that smoking produces exposure to diacetyl that is on average about 750 times higher than vaping." (Siegel)
*Referring to: Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 2016 Jun;124(6):733-9. [https://pubmed.ncbi.nlm.nih.gov/26642857/ doi: 10.1289/ehp.1510185]. Epub 2015 Dec 8. PMID: 26642857; PMCID: PMC4892929.

===2016: Comments RE: [https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===
*"The mice were severely overdosed with nicotine, up to the lethal levels for mice, and a huge amount above what any human vaper would get...Regarding the relevance to human health, nicotine poisoning poses normally no risk to vapers or smokers because if nicotine concentrations start to rise above their usual moderate levels, there is an advance warning in the form of nausea which makes people stop nicotine intake long before any dangerous levels can accrue. (Mice in these types of experiments do not have that option)." (Hajek)
*Referring to: Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax. 2016 Dec;71(12):1119-1129. [https://pubmed.ncbi.nlm.nih.gov/27558745/ doi: 10.1136/thoraxjnl-2015-208039]. Epub 2016 Aug 24. PMID: 27558745; PMCID: PMC5136722.

===2015: Comments RE: [https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/5dfe1e98-3100-4102-a425-a647b9459456 Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model]===
*" In other words, to obtain the same exposure in humans the e-cig user should take 11000 – 13000 puffs per day. Assuming 8 hours of sleep per day, in order to acquire such a high number of puffs e-cig users would need to take 11-13 puffs per minute and thus practically take an e-cig puff with each breath. In conclusion we recommend that the results of the discussed study should be interpreted with caution and that more studies with more realistic levels of e-liquid exposure should be conducted." (Mukhin, Rose)
*Referring to: Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. (2015) Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. PLoS ONE 10(2): e0116861. https://doi.org/10.1371/journal.pone.0116861

=Retractions by Journal=

===2025: Comments RE: [https://academic.oup.com/ntr/article/28/2/314/8320356 Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review]===
*Therefore, the Editor is retracting this article because the article was accepted with an undisclosed conflict of interest that would have changed the editorial decision.
**Referring to: Xingyu Liu, Rana Tayyarah, Xiang Chang, Xin Gao, Lisha Chen, Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review, Nicotine & Tobacco Research, 2025; ntaf189, https://doi.org/10.1093/ntr/ntaf189.

===2024: Comments RE: [https://www.science.org/content/article/questionable-firms-tempt-young-doctors-with-easy-publications Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES]===
*"The more they looked at the article, the more problems they saw. The work was based on data from an annual survey on health and nutrition by the U.S. Centers for Disease Control and Prevention (CDC), but the reported number of survey respondents was inexplicably off by an order of magnitude—the survey is completed by about 5000 people a year, but the paper cited 266,058 respondents from 2015 to 2018. The authors also failed to report whether the difference in age of stroke onset between vapers and traditional smokers could simply be due to vapers being younger overall. And those were just a few of the obvious issues, according to Cohen and Foxon, who alerted both the authors and the journal to their concerns." (Joelving)
*See Also: [https://twitter.com/FloeFoxon/status/1786522387338465755 Tweetorial] (Foxon) and [https://pubpeer.com/publications/1F118DC9A92A4FC13507BB5448462D PubPeer] (Richardson and others - 4 comments)
*Retracted: 18th of December, 2025
**Referring to: Patel U, Patel N, Khurana M, Parulekar A, Patel A, Ortiz JF, Patel R, Urhoghide E, Mistry A, Bhriguvanshi A, et al. Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES. Neurology International. 2022; 14(2):441-452. https://doi.org/10.3390/neurolint14020037

===2022: Original: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239491/ Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study]===
*Citation: RC, Dawoodi S, Fabara SP, Asad M, Khayyat A, Chandramohan S, Aslam A, Unachukwu N, Nasyrlaeva B, Jaiswal R, Chowdary SB, Malik P, Rabbani R. Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study. Gastroenterology Res. 2022 Jun;15(3):113-119. doi: 10.14740/gr1490. Epub 2022 Jun 22. Retraction in: Gastroenterology Res. 2023 Jun;16(3):201. PMID: 35836707; PMCID: PMC9239491.
*2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284643/ Retraction Notice to “Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study”]
**Media - Filter: [https://filtermag.org/vaping-liver-disease-study-retracted/ Journal Retracts Study That Linked Vaping to Liver Disease]

===2022: Original: [https://reason.com/wp-content/uploads/2023/01/1438-9260-6-PB.pdf Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study]===
*Citation: Chidharla A, Agarwal K, Abdelwahed S, Bhandari R, Singh A, Rabbani R, Patel K, Singh P, Mehta D, Manaktala PS, Pillai S, Gupta S, Koritala T. Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study. World J Oncol. 2022 Feb;13(1):20-26. doi: 10.14740/wjon1438. Epub 2022 Feb 8. Retraction in: World J Oncol. 2022 Dec;13(6):417. PMID: 35317331; PMCID: PMC8913014.
*2022: [https://reason.com/wp-content/uploads/2023/01/1562-10357-1-PB.pdf Retraction Notice to “Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study”]
**Media - Reason: [https://reason.com/2023/01/04/a-medical-journal-retracts-a-2022-study-that-linked-vaping-to-cancer/ A Medical Journal Retracts a 2022 Study That Linked Vaping to Cancer]

===2019: Original: [https://www.ahajournals.org/doi/10.1161/JAHA.119.012317 Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]===
**Citation: Bhatta DN, Glantz SA. Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health. J Am Heart Assoc. 2019 Jun 18;8(12):e012317. doi: 10.1161/JAHA.119.012317. Epub 2019 Jun 5. Retraction in: J Am Heart Assoc. 2020 Feb 18;9(4):e014519. Erratum in: J Am Heart Assoc. 2019 Nov 5;8(21):e002313. PMID: 31165662; PMCID: PMC6645634.
*2020: [https://www.ahajournals.org/doi/10.1161/JAHA.119.014519 Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]
**[https://pubpeer.com/publications/F177153E02CA8B3E7B9E70BC8DB204 PubPeer]
**Media - USA Today: [https://www.usatoday.com/story/news/health/2020/02/20/nyu-scientists-others-call-taxpayer-funded-ucsf-vaping-study-probe/4805323002/ A study claimed vaping doubles risk for heart attacks. It's been retracted for being 'unreliable']

===2019: Original: [https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.29148 Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non–small cell lung cancer]===
**Citation: Liu Z, Lu C, Zhao G, Han X, Dong K, Wang C, Guan JZ, Wang Z. Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non-small cell lung cancer. J Cell Biochem. 2019 Oct;120(10):18370-18377. doi: 10.1002/jcb.29148. Epub 2019 Jun 12. Retraction in: J Cell Biochem. 2024 Apr 5. doi: 10.1002/jcb.30562. PMID: 31190333.
*[https://pubmed.ncbi.nlm.nih.gov/38577886/ PubMed Retraction]
*Retracted 2024: [https://pubpeer.com/publications/D500DE74010B291A7B27CBB9083FEA PubPeer Comment about retraction]

=Retractions by Author Request=

===2025: [https://link.springer.com/article/10.1038/s41388-024-03269-w Retraction Note: Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis]===
"The authors have retracted this article. After publication, concerns were raised regarding highly similar ex vivo brain images in Figs. 2A (Vehicle, right), 5A (miR-4466 inh., left) and 6E (-Nic.+Stat3i, right). The authors thoroughly checked the underlying data and found that the data were mismanaged, which may have affected the presented results.
**Citation: Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R, Singh R, Li W, Topaloglu U, Ruiz J, Watabe K. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022 May;41(22):3079-3092. doi: 10.1038/s41388-022-02322-w. Epub 2022 Apr 23. Retraction in: Oncogene. 2025 Jan 9. doi: 10.1038/s41388-024-03269-w. PMID: 35461327; PMCID: PMC9135627.

===2024: [https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00998-w The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis]===
**Citation: Tehrani, H., Rajabi, A., Ghelichi- Ghojogh, M. et al. RETRACTED ARTICLE: The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis. Arch Public Health 80, 240 (2022). https://doi.org/10.1186/s13690-022-00998-w
*[https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-024-01345-x Retraction Notice]: The authors have retracted this article because it incorrectly reports the results of several studies included in their review. This impacts the overall results of their meta-analysis. The authors have been offered the opportunity to re-analyse their findings and to submit an updated version to the journal, which will be subjected to robust peer review.

===2024: [https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814489 RETRACTED: Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking A Randomized Clinical Trial]===
**Citation: Liu Z. Notice of Retraction: Lin HX et al. Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. 2024 May 1;184(5):589. doi: 10.1001/jamainternmed.2024.1125. PMID: 38551593.
*[https://pubpeer.com/publications/A3736116C180E920966659A2AEA32F Author's retraction request post on PubPeer]
*Retraction Watch: [https://retractionwatch.com/2024/04/02/paper-claiming-vaping-tops-nicotine-gum-for-smoking-cessation-retracted-from-jama-journal/ Paper claiming vaping tops nicotine gum for smoking cessation retracted from JAMA journal]

=Suggestions to add to this page=

===2026: [https://www.sciencedirect.com/science/article/pii/S2213538325000591 RETRACTED: Evidence on vaping e-cigarettes as a risk factor for cancer: A systematic review]===

===2025: [https://pmc.ncbi.nlm.nih.gov/articles/PMC12708306/ Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey]===

===2024: [https://www.sciencemediacentre.org/expert-reaction-to-epigenetic-changes-in-cells-of-smokers-and-vapers/ expert reaction to epigenetic changes in cells of smokers and vapers]===

===2024: [https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===

===2022: [https://link.springer.com/article/10.1007/s11739-022-03163-x A tale of flawed e-cigarette research undetected by defective peer review process]===
*[https://www.coehar.org/anti-vaping-narrative-driven-by-low-quality-science-goes-undetected-by-editorial-quality-checks/ Anti-vaping narrative driven by low quality science goes undetected by editorial quality checks]

===2022: [https://www.mdpi.com/2305-6304/10/12/714 Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===

===2025: [https://www.nature.com/articles/s41467-025-59975-w Retraction Note: Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung]===
*"The authors have retracted this article. After publication, concerns were raised regarding highly similar images in the figures, specifically..."

===2025: RE [https://www.amjmed.com/article/S0002-9343(24)00796-4/fulltext Scientific Inaccuracies in Smoking Cessation Guidance]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===

===2025: RE [https://www.pubpeer.com/publications/B604AE5B635D7A1A0E0A6571FDEF16 Exposure to third hand e-cigarette vapour impairs cognitive function in young mice]===

===2025: [https://www.qeios.com/read/FDX7P3 Exposure to Benzene, Toluene, and Xylenes from Electronic Cigarette Use Compared to Working Environment Permissible Exposure Limits: A Risk Assessment Analysis of a Recent Publication]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntae232/7780360?login=false Electronic cigarettes during pregnancy: Another tool for discontinuing smoking?]===
*note: this isn't formatted for placement in the correct section
*[https://x.com/ArielleSelya/status/1839786888099463656 Twitter thread]

===2025: [https://www.qeios.com/read/9XT2GU Critical Appraisal of Exposure Studies on E-Cigarette Aerosols Generated by High-Powered Devices]===
*note: this isn't formatted for placement in the correct section

===[https://pubmed.ncbi.nlm.nih.gov/31712273/ Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes]===
*note: this isn't formatted for placement in the correct section
*[https://www.sciencemediacentre.org/expert-reaction-to-case-study-linking-lung-inflammation-to-vaping-in-a-16-year-old/ Expert Comments]

===Paper: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00253 Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]===
*Comment: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00367 Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]
*Response: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00414 Response to Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]

===Paper: [https://gh.bmj.com/content/9/2/e013866 Pharmaceuticalisation as the tobacco industry’s endgame]===
*Comment: [https://pubpeer.com/publications/374B1C6D333BD84814E878DF9D1611 Title: Errors in one sentence - oversights or indicators of other problems?]

===[https://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/233-pm A new study reports that e-cigarettes emit toxins to the environment but the authors did not really find any…]===

 

[[File:Retracted 2.png|center|]]
[[Category:Studies, Surveys, and Papers]]

Nicotine / THR - Guides for Healthcare and Social Services Professionals

2026-02-26T04:14:38Z

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[[file:Healthcare and Social Services.png|center]]
 

<big>'''Reminder: Using NRT (Nicotine Replacement Therapy) is a form of Tobacco Harm Reduction (THR).'''</big>
 
 

='''Healthcare Professionals'''=

==Doctors, Nurses, Clinics, Hospitals==

===ENDS (Electronic Nicotine Delivery Systems), E-Cigarettes, Vapes===

====[https://www.cebm.ox.ac.uk/research/electronic-cigarettes-for-smoking-cessation-cochrane-living-systematic-review-1 Electronic Cigarettes for Smoking Cessation: Cochrane Living Systematic Review]====
*Click the link on the page for the latest "Briefing for healthcare professionals."

====[https://rise.articulate.com/share/cbY8v5PuSpLx-wprJxjplKns5aHtlFHO#/ Tobacco Harm Reduction Training Course]====
*This course educates physicians, nurses, dentists, pharmacists, and other healthcare workers about far less hazardous products that deliver nicotine/tobacco satisfaction together with a small fraction of the health risks of smoking. This course does not promote any medical intervention. Rather, it educates health professionals so that they are in a better position to offer lifestyle options, especially to smokers unable or unwilling to quit nicotine/tobacco entirely.
*This course contains the following tobacco harm reduction (THR) topics:
**Nicotine: Correcting Misperceptions
**Smoking and Vaping in the U.S.
**Risks of Smokeless Tobacco Use and Cigar Smoking Explained
**Risks of E-Cigarettes and Heat-Not-Burn Tobacco Explained
**Tobacco Harm Reduction Can Work: Evidence From Around the World

====[https://costed.uea.ac.uk/ COSTED Toolkit]====
*The COSTED intervention has been developed through research to help deliver effective smoking cessation support to people who smoke attending the emergency department (ED).
*This toolkit has been designed by researchers at the University of East Anglia to help healthcare professionals implement the COSTED intervention.

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

====[https://www.ncsct.co.uk/library/view/pdf/NCSCT-maximising-impact-briefing.pdf NCSCT Maximising the impact of stop smoking services: latest evidence and best practice]====
*This briefing identifies principles and evidence-based actions to increase the impact of Local Stop Smoking Services (LSSS). Informed by a review of evidence and best practice, it aims to assist with planning and delivery processes to ensure decisions are based on evidence to further maximise the impact of services.
*Ensure tobacco dependence treatment and stop smoking support are embedded in key settings with direct contact with people who smoke, with a focus on priority groups. This includes community services, hospitals and other health and social care settings.
*Provide access to all first-choice stop smoking aids including combination Nicotine Replacement Therapy (NRT), nicotine vapes and nicotine analogues (varenicline and cytisine).

====2025: [https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1463 National Comprehensive Cancer Network (NCCN)]====
*E-cigarettes are non-combustible tobacco products that deliver nicotine through heated aerosols for inhalation. The use of e-cigarettes is often referred to as vaping.
*There is accumulating evidence from randomized clinical trials and systematic reviews that e-cigarettes are effective for smoking cessation.
*E-cigarettes are addictive and they contain and produce harmful chemicals.
*If a patient has already quit cigarette smoking through the use of vaping, providers should support continued smoking abstinence. As the patient becomes more confident about maintaining long-term smoking abstinence, the provider can encourage cessation of e-cigarettes, but not at the risk of relapse back to cigarette smoking.

====2025: [https://www.sciencedirect.com/science/article/pii/S0828282X25000091 Canadian Cardiovascular Society Clinical Practice Update on Contemporary Approaches to Smoking Cessation]====
*E-cigarettes are potentially valuable harm reduction tools for adults who smoke, especially those who are unable to use or quit with conventional evidence-based tobacco cessation treatments. Meta-analyses of randomized trials report strong evidence that e-cigarettes are effective to help people to quit smoking, with minimal harms when used short-term (6-12 months). Nicotine-containing e-cigarettes are effective for smoking cessation, and increase the odds of quitting by 2-3 times compared with placebo.
*They are effective for smoking cessation and adverse events are infrequent within 1-year follow-up. There are no e-cigarettes licensed or regulated as a medical product, but they are available as a consumer product. There is growing concern about the recreational use of e-cigarettes by nonsmokers, especially youth, who initiate nicotine use through e-cigarettes.

====2024: [https://www.brit-thoracic.org.uk/quality-improvement/clinical-statements/medical-management-of-inpatients-with-tobacco-dependency/ British Thoracic Society - Medical Management of inpatients with tobacco dependency]====
*(Click the link to download the main document.)
*"Building block 5: provide accurate and consistent information on Vaping
**Nicotine vapes deliver high dose fast-acting nicotine which can help to alleviate withdrawal and urges to smoke
**Vaping is an effective tool in the treatment for tobacco dependency and can be used to support patients during a hospital admission and to help achieve long term abstinence
**When using nicotine vapes as part of their tobacco dependency treatment plan, inpa�tients should be advised to switch entirely from smoking to vaping (and NRT) to maximise the harm reduction, both during the admission and after discharge
**If provided in the inpatient setting, nicotine vapes should be used alongside combination NRT as patients may not be able to use the vape at certain times or in certain environments (eg, the internal hospital building)
**Vaping is more likely to be effective when provided alongside behaviour change support from a TDA during the hospital admission and after discharge
**Vaping is not risk free. Patients that use vaping as part of their tobacco dependency treatment plan should be advised to reduce their vape usage at the appropriate time and ultimately to stop vaping, when there is minimal risk of a relapse to smoking
**People who do not smoke, should not vape. Vapes should not be used by any patients under 18 years of age or patients who do not smoke
**Inform patients who use nicotine vapes as part of their tobacco dependency treatment plan that vaping products are regulated under Tobacco and Related Product Regulations 2016 (TRPR). Adverse events related to vape products need to be reported to the Medicines and Healthcare products Regulatory Agency (MHRA) and that vaping products should only be purchased from reputable sources. Additional information on reputable sources can be sought from local government stop smoking services
**From an environmental perspective, avoid single-use products
**Vapes should not be used when using home oxygen therapy"

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2024: AU: [https://www.tga.gov.au/resources/resource/guidance/guidance-use-vapes-smoking-cessation-or-management-nicotine-dependence Guidance on the use of vapes for smoking cessation or the management of nicotine dependence]====
*This page contains practical guidance to assist medical and nurse practitioners with prescribing therapeutic vapes for smoking cessation or the management of nicotine dependence.
*"For persons who have unsuccessfully tried to stop smoking with approved pharmacotherapies, but continue to be motivated to stop smoking, therapeutic vapes may be a reasonable intervention."

====2024: Canada (CAMH): [https://intrepidlab.ca/en/Documents/VECTOR%20Guidance%20Resource%20FINAL.pdf E-CIGARETTE USE EVIDENCE-INFORMED GUIDANCE ON HARMS AND BENEFITS]====
*"There is interest among health care practitioners and Health Canada regarding the scientific evidence on the harms and benefits of using e-cigarette products at the individual and population level. The recommendations developed through this project examine existing evidence on the health impacts of e-cigarette use to conduct a nuanced harm-benefit analysis. The recommendations are intended as a decision-making and guidance resource for both healthcare practitioners and for people who either use, or are thinking of using e-cigarettes."
*[https://intrepidlab.ca/en/Documents/VECTOR_Summary_of_Recommendations_FINAL.pdf Health Effects of E-Cigarette Use: Summary of Recommendations]

====2024: [https://wa-provider.kaiserpermanente.org/static/pdf/public/guidelines/tobacco.pdf Kaiser Permanente - Tobacco and Nicotine Cessation Guideline]====
*There is emerging, high-quality evidence that switching completely from conventional cigarettes to ecigarettes is an effective intervention for harm reduction and for smoking cessation, at least in the short term. Users of e-cigarettes are exposed to fewer (and lower levels of) toxic substances than users of conventional cigarettes, and while not without health risks, e-cigarette use is generally less harmful than smoking cigarettes.

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

====2023: Video by Dr. Oyston: [https://oyston.com/blog/safer-nicotine/ A Physicians Guide to Safer Nicotine Products for People Who Smoke]====
*Covers smoking, stigma, facts about nicotine, and how to help people who smoke.

====2023: [https://www.physiciansresearchinstitute.org/hey-doc-do-you-really-want-to-stop-your-patients-from-smoking-2/ Hey Doc: Do You Really Want to Stop Your Patients From Smoking?]====
*Explains the various types of reduced-risk nicotine products and how they might help some people stop smoking.
**See Also: [https://www.physiciansresearchinstitute.org/harm-reduction/ Harm Reduction]

====2020 [https://web.archive.org/web/20230515102535/https://ash.org.uk/uploads/MHSP-ecig-briefing-2020-v2.pdf Use of electronic cigarettes by people with mental health problems: A guide for health professionals.]====
*This resource has been produced by the Mental Health and Smoking Partnership22 and is intended to provide mental health professionals with a summary of the evidence on e-cigarettes as well as suggested responses to questions service users may ask. It is primarily aimed at professionals working in England but can be used by anyone across the UK.

====2017: [https://www.rcgp.org.uk/representing-you/policy-areas/e-cigarettes E-cigarettes and non-combustible inhaled tobacco products]====
*"This updated guidance seeks to give clinicians the current understanding about where ECs may help with smoking cessation and the current understanding in regards to their safety."

====2016: [https://colinmendelsohn.com.au/wp-content/uploads/2018/12/Mendelsohn_CP._Electronic_cigarettes._Respiratory_MedicineToday_2016.pdf Electronic cigarettes A guide for discussions with patients]====
*"Electronic cigarettes (ECs) may be an option for smokers who want to quit but who have failed using first-line therapies. GPs can have a role in providing patients with reliable information about ECs, supporting them in a quit attempt and prescribing nicotine solution."

===Nicotine or Traditional NRT===

====2023: [https://www.roshreview.com/blog/inclusive-language-for-medical-education-and-qbanks-an-evolving-guide/ Inclusive Language for Medical & Health Education: An Evolving Guide]====
*Covers how to talk with or about patients

====2020: [https://link.springer.com/article/10.1007/s11606-020-06172-8 Nicotine Risk Misperception Among US Physicians]====
*Covers misperceptions physicians have about nicotine.
**See also: [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791164 Communication Between US Physicians and Patients Regarding Electronic Cigarette Use]

====2007: [https://www.sciencedirect.com/science/article/abs/pii/S0306460307000457 Advice on using over-the-counter nicotine replacement therapy-patch, gum, or lozenge-to quit smoking]====
*Explains how to use, clears up misperceptions, and discusses safety

===Additional Considerations for Healthcare Providers===

====2025: [https://www.edwardanselmmd.com/tobacco-cessation-as-a-profit-center Tobacco Cessation as a Profit Center]====
*"A close study of the economics of tobacco cessation can support a reconceptualization of tobacco cessation as a profit center. Clinical guidelines describe an evidence-based intervention that can be provided to every tobacco user at every visit, regardless of their readiness to change."

====2025: [https://www.sciencedirect.com/science/article/pii/S2773065425000677 A Multi-Institutional Evaluation of Billing for Tobacco Cessation Services: Opportunities to Improve Quality and Enhance Revenue Capture]====
*"Billing of cessation services is consistently below 2% across the medical centers studied suggesting substantial opportunities to improve quality and increase revenue."

====2024: [https://emj.bmj.com/content/41/5/276 Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial]====
*"In this study of adults who smoke and who were attending the ED, an intervention comprising brief advice, provision of an e-cigarette starter kit and referral to stop smoking services resulted in significantly increased sustained smoking abstinence 6 months later compared with those signposted to stop smoking services. Providing smoking cessation support in the ED should be considered to reach groups of the population that may not routinely engage with stop smoking services but have the most to gain from stopping smoking."

*More information: 2023: [https://bmjopen.bmj.com/content/13/1/e064585 Cessation of smoking trial in the emergency department (CoSTED): protocol for a multicentre randomised controlled trial]

==Supporting People Before, During, and After Pregnancy==

===ENDS (Electronic Nicotine Delivery Systems), E-Cigarettes, Vapes===

====[https://ash.org.uk/resources/smokefree-nhs/smoking-in-pregnancy-challenge-group/using-e-cigarettes-before-during-and-after-pregnancy Using e-cigarettes before, during and after pregnancy]====
*Provides links to guides and infographics for maternity and healthcare professionals. Also, it provides information for pregnant people and their families.

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular. Includes a section on pregnancy.

==Supporting People Living With Mental Health Conditions==

====2025: [https://www.youtube.com/watch?v=EwTXP9phDxk Recording: ASH webinar on preparing mental health settings for the disposable vapes ban]====
*This ASH webinar focussed on preparing mental health trusts for the upcoming single-use (disposable) vapes ban, bringing together case studies from trusts and the prison estate.

====2024: [https://rwjms.rutgers.edu/sites/default/files/2024-04/2012_lahl.pdf The Learning About Healthy Living: Tobacco and You (LAHL)]====
*“The aim of this treatment manual is to provide a format to address tobacco for those with mental health conditions, defined as those with a mental health or substance use disorder.” “This 2024 Version of LAHL includes many updates including two new sessions on topics of harm reduction, e-cigarettes and vaping.”

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2020: [https://www.gov.uk/government/publications/e-cigarettes-use-by-patients-in-nhs-mental-health-organisations/using-electronic-cigarettes-in-nhs-mental-health-organisations Guidance Using electronic cigarettes in NHS mental health organisations]====
*"Recommendations for care
**Provide clear information to both staff and patients about the difference between vaping and smoking and the associated risks of both.
**Encourage patients to stop smoking or to abstain temporarily and offer behavioural support and prescribed smoking medications in support of any quit attempt.
**Ensure patients have access to vaping products and consider whether to provide them proactively to patients who smoke.
**Do not discourage patients using their own e-cigarettes in a quit attempt or when trying to abstain from smoking temporarily (unless an individual risk assessment suggests it is unsafe to do so).
**Nicotine replacement supports temporary abstinence and quitting smoking, so do not rush patients to stop vaping as this may increase the risk of relapse to smoking.
**Where patients are admitted who already vape, allow them to continue to use e-cigarettes. They do not need a stop smoking intervention unless they are also smoking cigarettes.
**NHS trusts that provide stop smoking support should consider offering a wider package of support to the family at home, such as information on referral to local stop smoking services.
**It is an offence to sell a nicotine inhaling product to anyone under the age of 18 [in the UK - check local laws outside of the UK] or to buy one on their behalf. Public Health England (PHE) does not recommend the use of e-cigarettes by anyone under 18."

==Supporting People Living With Substance or Alcohol Use Disorders==

===Training===

====2024: [https://rwjms.rutgers.edu/sites/default/files/2024-04/2012_lahl.pdf The Learning About Healthy Living: Tobacco and You (LAHL)]====
*“The aim of this treatment manual is to provide a format to address tobacco for those with mental health conditions, defined as those with a mental health or substance use disorder.” “This 2024 Version of LAHL includes many updates including two new sessions on topics of harm reduction, e-cigarettes and vaping.”

===Tobacco Harm Reduction===

====2024: Webinar from the Safer From Harm Coalition: [https://www.rstreet.org/events/new-approaches-to-tobacco-smoking-cessation-among-people-who-use-drugs/ New Approaches to Tobacco Smoking Cessation Among People Who Use Drugs]====
*"Some clinicians and practitioners who work with people who use drugs are integrating patient-centered tobacco harm reduction into their approaches. This panel will showcase two such people, who will discuss the current evidence about reduced-risk nicotine products, how they decide whether or when to explore tobacco harm reduction with patients and clients, and how people who use drugs respond to these concepts."

====2022: [https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/guidelines/tobacco-guide.pdf Integrating Tobacco Use Disorder Interventions in Addiction Treatment ]====
*“If smokers want to try ENDS, they should be encouraged to switch completely as the dual use of ENDS and combustible cigarettes may undermine efforts at cessation. For patients that exclusively use ENDS, motivational interviewing should still be used to promote cessation and to prevent the patient from relapsing to combustible cigarettes.”

==Supporting Veterans==

===2022: [https://www.pbm.va.gov/PBM/AcademicDetailingService/Documents/508/IB10-1150%20TUD%20Provider%20TobaccoUseProviderGuide%20P96912.pdf Tobacco Use Disorder A Provider's Guide to Counseling and Medication Treatment to Help Veterans with Tobacco Cessation]===
*The section on ENDS (vaping) is not very good. It makes them sound more harmful than vaping is known to be, and it doesn't provide any comparison to smoking tobacco. Due to a lack of finding veteran-specific guides, this one is included. Providers are encouraged to look at some of the other resources available on this page.

==Cessation Services - Public Health==

===Training Programs===

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2019: NCSCT (UK) [https://www.ncsct.co.uk/library/view/pdf/NCSCT%20Standard%20Treatment%20Programme.pdf STANDARD TREATMENT PROGRAMME A guide to providing behavioural support for smoking cessation]====
*Includes THR as one of many options to help people stop smoking
*[https://www.ncsct.co.uk/publications/category/behavioural-support-briefings Links to complementary materials to their guide]

===Information Guides===

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

====Year?: [https://www.ncsct.co.uk/library/view/pdf/Trial%20of%20E-Cigarettes%20%28TEC%29%20briefing.pdf Information for specialist stop-smoking services that are considering providing e-cigarette starter packs: recommendations from the Trial of Ecigarettes (TEC)]====
* “As e-cigarette starter packs are an effective and cost effective treatment, SSS should include them among their treatment options.”

==Cessation Services - Nontraditional such as Vape Shops==

===Exploring the Possibility===

====2024: [https://pubmed.ncbi.nlm.nih.gov/38685876/ Developing a vape shop-based smoking cessation intervention: a Delphi study]====
*"There was consensus that the service should comprise both product (98%) and behavioural support (97%)...Delivering vape-shop based smoking cessation interventions could help to maximise the effectiveness of e-cigarettes for quitting smoking."

====2023: [https://pubmed.ncbi.nlm.nih.gov/38069625/ How should a vape shop-based smoking cessation intervention be delivered? A qualitative study]====
*The results suggest that the intervention should be delivered by vape shop workers with mandatory training with the support of stop smoking service providers...The intervention should comprise both technical guidance on using a vape and behavioural support to prevent a return to smoking.

===Stop Smoking Service and Vape Shops - A Team Effort===

====Year?: [https://www.ncsct.co.uk/library/view/pdf/Working%20with%20vape%20shops%2002.10.18%20update.pdf Working with vape shops: A guide for commissioners and stop smoking services]====
*Most staff in these shops are vapers, having stopped smoking themselves, and they are generally keen to help others become ex-smokers.
*[https://www.ncsct.co.uk/publications/working_with_vape_shops Alternative link]

='''Social Services and Social Care'''=

==General==

====2024: [https://gsthr.org/resources/briefing-papers/smoking-and-vulnerable-populations-supporting-smoking-cessation-and-tobacco-harm-reduction-in-social-work/ Smoking and vulnerable populations: supporting smoking cessation and tobacco harm reduction in social work]====
*"Like doctors, community nurses, midwives, psychologists, and psychotherapists, social workers can have a significant influence, both over people’s decisions and their overall wellbeing. Serving as the initial – and in some cases only – point of contact with marginalised communities, social workers could therefore play an important role in reducing the prevalence of smoking."

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

==Supporting People Experiencing Unstable Housing==

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

==Adoption and Foster Care - “Substitute Carers”==

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

====2020: Together4Children: [https://www.fosteringhandbook.com/telford/user_controlled_lcms_area/uploaded_files/T4C%20Smoking%20-%20Fostering%20and%20Adoption.pdf Smoking (including use of e-cigarettes) (Fostering, Adoption Special Guardians) Policy and Procedure]====
* “Due to the recognised differences on health impacts, Together4Children treat tobacco smoking and the use of electronic cigarettes differently as reflected in the following policy…Together4Children recognises the low risk to children and does not view the use of ecigarettes as a reason to exclude prospective foster carers/adopters, purely on this basis. However, prospective carer/adopter’s use of e-cigarettes will be discussed at the initial visit, during the full assessment and monitored via the review process. “

====2019: Worcestershire Children First Fostering (WCFF): [https://www.worcestershire.gov.uk/sites/default/files/2022-11/64256_Smoking_and_Vaping_V01.pdf Smoking and E-Cigarettes (Vaping) Policy for Staff and Foster Carers]====
*“Social Workers should support foster carers to give up smoking by signposting them to organisations which can help them…E-cigarettes, also known as vaporisers, are not tobacco cigarettes. The use of them has become more wide spread in recent years and can provide a route for smokers to help them reduce or give up smoking.”

====2018: CoramBAAF: [https://proceduresonline.com/trixcms1/media/2965/corambaafpn68_reducingriskofenvironmentalsmoketolacandcarers.pdf PRACTICE NOTE 68 Reducing the risks of environmental tobacco smoke for looked after children and their carers]====
*“We would strongly recommend that all substitute carers should be proactively encouraged to stop smoking…The issue is therefore not one of banning prospective adopters and new carers, but of engaging with them, providing information and advice, and facilitating access to smoking cessation programmes…"
**Note: Covers us of vapor products

====2014: BAAF: [https://web.archive.org/web/20150317065142/http://www.baaf.org.uk/node/7583 BAAF - British Association for Adoption and Fostering]====
* “Agencies should therefore recognise the low risk to children and not see the use of e-cigarettes as a reason to preclude foster carers or adopters purely on this basis. Each circumstance should be risk assessed on an individual basis.”
**Note: This non-profit closed in 2015 - A new charity called CoramBAAF took its place.

='''Educators'''=

===[https://x.com/mikepesko/status/1363813387961044998 Michael F. Pesko]===
*"(1/Thread): Hey health policy/econ professors, ever considered adding an #ecig section to your health course? Here is a slide deck for you: http://bit.ly/3pCsIGV. Feel free to use any part of this in your own courses to spread knowledge about this important/interesting topic. #econtwitter" (Note: This doc always links to a clickable link for an updated version)

=Suggestions to add to this page=

===2025: [https://link.springer.com/article/10.1007/s11739-025-04131-x Two decades of global tobacco control: time for a rethink]===

Nicotine / THR - Guides for Healthcare and Social Services Professionals

2026-02-26T04:12:05Z

Skip: /* Suggestions to add to this page */

[[file:Healthcare and Social Services.png|center]]
 

<big>'''Reminder: Using NRT (Nicotine Replacement Therapy) is a form of Tobacco Harm Reduction (THR). THR is not an accurate term because there is a continuum of risk, and not all nicotine products contain tobacco. A more accurate term would be Smoking Harm Minimization (SHM).'''</big>
 
 

='''Healthcare Professionals'''=

==Doctors, Nurses, Clinics, Hospitals==

===ENDS (Electronic Nicotine Delivery Systems), E-Cigarettes, Vapes===

====[https://www.cebm.ox.ac.uk/research/electronic-cigarettes-for-smoking-cessation-cochrane-living-systematic-review-1 Electronic Cigarettes for Smoking Cessation: Cochrane Living Systematic Review]====
*Click the link on the page for the latest "Briefing for healthcare professionals."

====[https://rise.articulate.com/share/cbY8v5PuSpLx-wprJxjplKns5aHtlFHO#/ Tobacco Harm Reduction Training Course]====
*This course educates physicians, nurses, dentists, pharmacists, and other healthcare workers about far less hazardous products that deliver nicotine/tobacco satisfaction together with a small fraction of the health risks of smoking. This course does not promote any medical intervention. Rather, it educates health professionals so that they are in a better position to offer lifestyle options, especially to smokers unable or unwilling to quit nicotine/tobacco entirely.
*This course contains the following tobacco harm reduction (THR) topics:
**Nicotine: Correcting Misperceptions
**Smoking and Vaping in the U.S.
**Risks of Smokeless Tobacco Use and Cigar Smoking Explained
**Risks of E-Cigarettes and Heat-Not-Burn Tobacco Explained
**Tobacco Harm Reduction Can Work: Evidence From Around the World

====[https://costed.uea.ac.uk/ COSTED Toolkit]====
*The COSTED intervention has been developed through research to help deliver effective smoking cessation support to people who smoke attending the emergency department (ED).
*This toolkit has been designed by researchers at the University of East Anglia to help healthcare professionals implement the COSTED intervention.

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

====[https://www.ncsct.co.uk/library/view/pdf/NCSCT-maximising-impact-briefing.pdf NCSCT Maximising the impact of stop smoking services: latest evidence and best practice]====
*This briefing identifies principles and evidence-based actions to increase the impact of Local Stop Smoking Services (LSSS). Informed by a review of evidence and best practice, it aims to assist with planning and delivery processes to ensure decisions are based on evidence to further maximise the impact of services.
*Ensure tobacco dependence treatment and stop smoking support are embedded in key settings with direct contact with people who smoke, with a focus on priority groups. This includes community services, hospitals and other health and social care settings.
*Provide access to all first-choice stop smoking aids including combination Nicotine Replacement Therapy (NRT), nicotine vapes and nicotine analogues (varenicline and cytisine).

====2025: [https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1463 National Comprehensive Cancer Network (NCCN)]====
*E-cigarettes are non-combustible tobacco products that deliver nicotine through heated aerosols for inhalation. The use of e-cigarettes is often referred to as vaping.
*There is accumulating evidence from randomized clinical trials and systematic reviews that e-cigarettes are effective for smoking cessation.
*E-cigarettes are addictive and they contain and produce harmful chemicals.
*If a patient has already quit cigarette smoking through the use of vaping, providers should support continued smoking abstinence. As the patient becomes more confident about maintaining long-term smoking abstinence, the provider can encourage cessation of e-cigarettes, but not at the risk of relapse back to cigarette smoking.

====2025: [https://www.sciencedirect.com/science/article/pii/S0828282X25000091 Canadian Cardiovascular Society Clinical Practice Update on Contemporary Approaches to Smoking Cessation]====
*E-cigarettes are potentially valuable harm reduction tools for adults who smoke, especially those who are unable to use or quit with conventional evidence-based tobacco cessation treatments. Meta-analyses of randomized trials report strong evidence that e-cigarettes are effective to help people to quit smoking, with minimal harms when used short-term (6-12 months). Nicotine-containing e-cigarettes are effective for smoking cessation, and increase the odds of quitting by 2-3 times compared with placebo.
*They are effective for smoking cessation and adverse events are infrequent within 1-year follow-up. There are no e-cigarettes licensed or regulated as a medical product, but they are available as a consumer product. There is growing concern about the recreational use of e-cigarettes by nonsmokers, especially youth, who initiate nicotine use through e-cigarettes.

====2024: [https://www.brit-thoracic.org.uk/quality-improvement/clinical-statements/medical-management-of-inpatients-with-tobacco-dependency/ British Thoracic Society - Medical Management of inpatients with tobacco dependency]====
*(Click the link to download the main document.)
*"Building block 5: provide accurate and consistent information on Vaping
**Nicotine vapes deliver high dose fast-acting nicotine which can help to alleviate withdrawal and urges to smoke
**Vaping is an effective tool in the treatment for tobacco dependency and can be used to support patients during a hospital admission and to help achieve long term abstinence
**When using nicotine vapes as part of their tobacco dependency treatment plan, inpa�tients should be advised to switch entirely from smoking to vaping (and NRT) to maximise the harm reduction, both during the admission and after discharge
**If provided in the inpatient setting, nicotine vapes should be used alongside combination NRT as patients may not be able to use the vape at certain times or in certain environments (eg, the internal hospital building)
**Vaping is more likely to be effective when provided alongside behaviour change support from a TDA during the hospital admission and after discharge
**Vaping is not risk free. Patients that use vaping as part of their tobacco dependency treatment plan should be advised to reduce their vape usage at the appropriate time and ultimately to stop vaping, when there is minimal risk of a relapse to smoking
**People who do not smoke, should not vape. Vapes should not be used by any patients under 18 years of age or patients who do not smoke
**Inform patients who use nicotine vapes as part of their tobacco dependency treatment plan that vaping products are regulated under Tobacco and Related Product Regulations 2016 (TRPR). Adverse events related to vape products need to be reported to the Medicines and Healthcare products Regulatory Agency (MHRA) and that vaping products should only be purchased from reputable sources. Additional information on reputable sources can be sought from local government stop smoking services
**From an environmental perspective, avoid single-use products
**Vapes should not be used when using home oxygen therapy"

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2024: AU: [https://www.tga.gov.au/resources/resource/guidance/guidance-use-vapes-smoking-cessation-or-management-nicotine-dependence Guidance on the use of vapes for smoking cessation or the management of nicotine dependence]====
*This page contains practical guidance to assist medical and nurse practitioners with prescribing therapeutic vapes for smoking cessation or the management of nicotine dependence.
*"For persons who have unsuccessfully tried to stop smoking with approved pharmacotherapies, but continue to be motivated to stop smoking, therapeutic vapes may be a reasonable intervention."

====2024: Canada (CAMH): [https://intrepidlab.ca/en/Documents/VECTOR%20Guidance%20Resource%20FINAL.pdf E-CIGARETTE USE EVIDENCE-INFORMED GUIDANCE ON HARMS AND BENEFITS]====
*"There is interest among health care practitioners and Health Canada regarding the scientific evidence on the harms and benefits of using e-cigarette products at the individual and population level. The recommendations developed through this project examine existing evidence on the health impacts of e-cigarette use to conduct a nuanced harm-benefit analysis. The recommendations are intended as a decision-making and guidance resource for both healthcare practitioners and for people who either use, or are thinking of using e-cigarettes."
*[https://intrepidlab.ca/en/Documents/VECTOR_Summary_of_Recommendations_FINAL.pdf Health Effects of E-Cigarette Use: Summary of Recommendations]

====2024: [https://wa-provider.kaiserpermanente.org/static/pdf/public/guidelines/tobacco.pdf Kaiser Permanente - Tobacco and Nicotine Cessation Guideline]====
*There is emerging, high-quality evidence that switching completely from conventional cigarettes to ecigarettes is an effective intervention for harm reduction and for smoking cessation, at least in the short term. Users of e-cigarettes are exposed to fewer (and lower levels of) toxic substances than users of conventional cigarettes, and while not without health risks, e-cigarette use is generally less harmful than smoking cigarettes.

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

====2023: Video by Dr. Oyston: [https://oyston.com/blog/safer-nicotine/ A Physicians Guide to Safer Nicotine Products for People Who Smoke]====
*Covers smoking, stigma, facts about nicotine, and how to help people who smoke.

====2023: [https://www.physiciansresearchinstitute.org/hey-doc-do-you-really-want-to-stop-your-patients-from-smoking-2/ Hey Doc: Do You Really Want to Stop Your Patients From Smoking?]====
*Explains the various types of reduced-risk nicotine products and how they might help some people stop smoking.
**See Also: [https://www.physiciansresearchinstitute.org/harm-reduction/ Harm Reduction]

====2020 [https://web.archive.org/web/20230515102535/https://ash.org.uk/uploads/MHSP-ecig-briefing-2020-v2.pdf Use of electronic cigarettes by people with mental health problems: A guide for health professionals.]====
*This resource has been produced by the Mental Health and Smoking Partnership22 and is intended to provide mental health professionals with a summary of the evidence on e-cigarettes as well as suggested responses to questions service users may ask. It is primarily aimed at professionals working in England but can be used by anyone across the UK.

====2017: [https://www.rcgp.org.uk/representing-you/policy-areas/e-cigarettes E-cigarettes and non-combustible inhaled tobacco products]====
*"This updated guidance seeks to give clinicians the current understanding about where ECs may help with smoking cessation and the current understanding in regards to their safety."

====2016: [https://colinmendelsohn.com.au/wp-content/uploads/2018/12/Mendelsohn_CP._Electronic_cigarettes._Respiratory_MedicineToday_2016.pdf Electronic cigarettes A guide for discussions with patients]====
*"Electronic cigarettes (ECs) may be an option for smokers who want to quit but who have failed using first-line therapies. GPs can have a role in providing patients with reliable information about ECs, supporting them in a quit attempt and prescribing nicotine solution."

===Nicotine or Traditional NRT===

====2023: [https://www.roshreview.com/blog/inclusive-language-for-medical-education-and-qbanks-an-evolving-guide/ Inclusive Language for Medical & Health Education: An Evolving Guide]====
*Covers how to talk with or about patients

====2020: [https://link.springer.com/article/10.1007/s11606-020-06172-8 Nicotine Risk Misperception Among US Physicians]====
*Covers misperceptions physicians have about nicotine.
**See also: [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791164 Communication Between US Physicians and Patients Regarding Electronic Cigarette Use]

====2007: [https://www.sciencedirect.com/science/article/abs/pii/S0306460307000457 Advice on using over-the-counter nicotine replacement therapy-patch, gum, or lozenge-to quit smoking]====
*Explains how to use, clears up misperceptions, and discusses safety

===Additional Considerations for Healthcare Providers===

====2025: [https://www.edwardanselmmd.com/tobacco-cessation-as-a-profit-center Tobacco Cessation as a Profit Center]====
*"A close study of the economics of tobacco cessation can support a reconceptualization of tobacco cessation as a profit center. Clinical guidelines describe an evidence-based intervention that can be provided to every tobacco user at every visit, regardless of their readiness to change."

====2025: [https://www.sciencedirect.com/science/article/pii/S2773065425000677 A Multi-Institutional Evaluation of Billing for Tobacco Cessation Services: Opportunities to Improve Quality and Enhance Revenue Capture]====
*"Billing of cessation services is consistently below 2% across the medical centers studied suggesting substantial opportunities to improve quality and increase revenue."

====2024: [https://emj.bmj.com/content/41/5/276 Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial]====
*"In this study of adults who smoke and who were attending the ED, an intervention comprising brief advice, provision of an e-cigarette starter kit and referral to stop smoking services resulted in significantly increased sustained smoking abstinence 6 months later compared with those signposted to stop smoking services. Providing smoking cessation support in the ED should be considered to reach groups of the population that may not routinely engage with stop smoking services but have the most to gain from stopping smoking."

*More information: 2023: [https://bmjopen.bmj.com/content/13/1/e064585 Cessation of smoking trial in the emergency department (CoSTED): protocol for a multicentre randomised controlled trial]

==Supporting People Before, During, and After Pregnancy==

===ENDS (Electronic Nicotine Delivery Systems), E-Cigarettes, Vapes===

====[https://ash.org.uk/resources/smokefree-nhs/smoking-in-pregnancy-challenge-group/using-e-cigarettes-before-during-and-after-pregnancy Using e-cigarettes before, during and after pregnancy]====
*Provides links to guides and infographics for maternity and healthcare professionals. Also, it provides information for pregnant people and their families.

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular. Includes a section on pregnancy.

==Supporting People Living With Mental Health Conditions==

====2025: [https://www.youtube.com/watch?v=EwTXP9phDxk Recording: ASH webinar on preparing mental health settings for the disposable vapes ban]====
*This ASH webinar focussed on preparing mental health trusts for the upcoming single-use (disposable) vapes ban, bringing together case studies from trusts and the prison estate.

====2024: [https://rwjms.rutgers.edu/sites/default/files/2024-04/2012_lahl.pdf The Learning About Healthy Living: Tobacco and You (LAHL)]====
*“The aim of this treatment manual is to provide a format to address tobacco for those with mental health conditions, defined as those with a mental health or substance use disorder.” “This 2024 Version of LAHL includes many updates including two new sessions on topics of harm reduction, e-cigarettes and vaping.”

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2020: [https://www.gov.uk/government/publications/e-cigarettes-use-by-patients-in-nhs-mental-health-organisations/using-electronic-cigarettes-in-nhs-mental-health-organisations Guidance Using electronic cigarettes in NHS mental health organisations]====
*"Recommendations for care
**Provide clear information to both staff and patients about the difference between vaping and smoking and the associated risks of both.
**Encourage patients to stop smoking or to abstain temporarily and offer behavioural support and prescribed smoking medications in support of any quit attempt.
**Ensure patients have access to vaping products and consider whether to provide them proactively to patients who smoke.
**Do not discourage patients using their own e-cigarettes in a quit attempt or when trying to abstain from smoking temporarily (unless an individual risk assessment suggests it is unsafe to do so).
**Nicotine replacement supports temporary abstinence and quitting smoking, so do not rush patients to stop vaping as this may increase the risk of relapse to smoking.
**Where patients are admitted who already vape, allow them to continue to use e-cigarettes. They do not need a stop smoking intervention unless they are also smoking cigarettes.
**NHS trusts that provide stop smoking support should consider offering a wider package of support to the family at home, such as information on referral to local stop smoking services.
**It is an offence to sell a nicotine inhaling product to anyone under the age of 18 [in the UK - check local laws outside of the UK] or to buy one on their behalf. Public Health England (PHE) does not recommend the use of e-cigarettes by anyone under 18."

==Supporting People Living With Substance or Alcohol Use Disorders==

===Training===

====2024: [https://rwjms.rutgers.edu/sites/default/files/2024-04/2012_lahl.pdf The Learning About Healthy Living: Tobacco and You (LAHL)]====
*“The aim of this treatment manual is to provide a format to address tobacco for those with mental health conditions, defined as those with a mental health or substance use disorder.” “This 2024 Version of LAHL includes many updates including two new sessions on topics of harm reduction, e-cigarettes and vaping.”

===Tobacco Harm Reduction===

====2024: Webinar from the Safer From Harm Coalition: [https://www.rstreet.org/events/new-approaches-to-tobacco-smoking-cessation-among-people-who-use-drugs/ New Approaches to Tobacco Smoking Cessation Among People Who Use Drugs]====
*"Some clinicians and practitioners who work with people who use drugs are integrating patient-centered tobacco harm reduction into their approaches. This panel will showcase two such people, who will discuss the current evidence about reduced-risk nicotine products, how they decide whether or when to explore tobacco harm reduction with patients and clients, and how people who use drugs respond to these concepts."

====2022: [https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/guidelines/tobacco-guide.pdf Integrating Tobacco Use Disorder Interventions in Addiction Treatment ]====
*“If smokers want to try ENDS, they should be encouraged to switch completely as the dual use of ENDS and combustible cigarettes may undermine efforts at cessation. For patients that exclusively use ENDS, motivational interviewing should still be used to promote cessation and to prevent the patient from relapsing to combustible cigarettes.”

==Supporting Veterans==

===2022: [https://www.pbm.va.gov/PBM/AcademicDetailingService/Documents/508/IB10-1150%20TUD%20Provider%20TobaccoUseProviderGuide%20P96912.pdf Tobacco Use Disorder A Provider's Guide to Counseling and Medication Treatment to Help Veterans with Tobacco Cessation]===
*The section on ENDS (vaping) is not very good. It makes them sound more harmful than vaping is known to be, and it doesn't provide any comparison to smoking tobacco. Due to a lack of finding veteran-specific guides, this one is included. Providers are encouraged to look at some of the other resources available on this page.

==Cessation Services - Public Health==

===Training Programs===

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2019: NCSCT (UK) [https://www.ncsct.co.uk/library/view/pdf/NCSCT%20Standard%20Treatment%20Programme.pdf STANDARD TREATMENT PROGRAMME A guide to providing behavioural support for smoking cessation]====
*Includes THR as one of many options to help people stop smoking
*[https://www.ncsct.co.uk/publications/category/behavioural-support-briefings Links to complementary materials to their guide]

===Information Guides===

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

====Year?: [https://www.ncsct.co.uk/library/view/pdf/Trial%20of%20E-Cigarettes%20%28TEC%29%20briefing.pdf Information for specialist stop-smoking services that are considering providing e-cigarette starter packs: recommendations from the Trial of Ecigarettes (TEC)]====
* “As e-cigarette starter packs are an effective and cost effective treatment, SSS should include them among their treatment options.”

==Cessation Services - Nontraditional such as Vape Shops==

===Exploring the Possibility===

====2024: [https://pubmed.ncbi.nlm.nih.gov/38685876/ Developing a vape shop-based smoking cessation intervention: a Delphi study]====
*"There was consensus that the service should comprise both product (98%) and behavioural support (97%)...Delivering vape-shop based smoking cessation interventions could help to maximise the effectiveness of e-cigarettes for quitting smoking."

====2023: [https://pubmed.ncbi.nlm.nih.gov/38069625/ How should a vape shop-based smoking cessation intervention be delivered? A qualitative study]====
*The results suggest that the intervention should be delivered by vape shop workers with mandatory training with the support of stop smoking service providers...The intervention should comprise both technical guidance on using a vape and behavioural support to prevent a return to smoking.

===Stop Smoking Service and Vape Shops - A Team Effort===

====Year?: [https://www.ncsct.co.uk/library/view/pdf/Working%20with%20vape%20shops%2002.10.18%20update.pdf Working with vape shops: A guide for commissioners and stop smoking services]====
*Most staff in these shops are vapers, having stopped smoking themselves, and they are generally keen to help others become ex-smokers.
*[https://www.ncsct.co.uk/publications/working_with_vape_shops Alternative link]

='''Social Services and Social Care'''=

==General==

====2024: [https://gsthr.org/resources/briefing-papers/smoking-and-vulnerable-populations-supporting-smoking-cessation-and-tobacco-harm-reduction-in-social-work/ Smoking and vulnerable populations: supporting smoking cessation and tobacco harm reduction in social work]====
*"Like doctors, community nurses, midwives, psychologists, and psychotherapists, social workers can have a significant influence, both over people’s decisions and their overall wellbeing. Serving as the initial – and in some cases only – point of contact with marginalised communities, social workers could therefore play an important role in reducing the prevalence of smoking."

====2024: [https://www.stopforlifeoxon.org/media/1145/adph-south-east-position-statement-on-vapes-2024v5.pdf SOUTH EAST OF ENGLAND POSITION STATEMENT ON VAPING 2024 ]====
*"There is guidance about working with children. Guidance for stop smoking services. Guidance for health and care professionals [includes sections on mental health and maternity] and for workplaces. The statement guides readers towards the evidence. It describes how to access training. It is referenced throughout and includes trusted sources for more information."

====2023: NCSCT (UK): [https://www.ncsct.co.uk/library/view/pdf/Vaping-a-guide-for-health-and-social-care-professionals.pdf Vaping: a guide for health and social care professionals]====
*This briefing is specifically written to summarise information and address issues relevant to health and social care professionals and to stop smoking practitioners in particular.

==Supporting People Experiencing Unstable Housing==

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

==Adoption and Foster Care - “Substitute Carers”==

====[https://elearning.ncsct.co.uk/england NCSCT Online Smoking Cessation Training Course (Free, must register)]====
*The training programme is founded upon evidence-based behaviour change techniques and includes practical interventions that will make a significant difference to the chances of your clients becoming permanent ex-smokers.
*The four Very Brief Advice (VBA) training modules are essential training for anyone who comes in to contact with smokers in primary care (VBA+), pregnant women (VBA for pregnant women), parents and carers of children (VBA on Secondhand Smoke), and those working with people experiencing homelessness (VBA+ for Homelessness Services).
*The training programme includes all of the information that you need to pass the online assessment. Upon successful completion of the assessment, you will become an NCSCT Certified Stop Smoking Practitioner.
*Includes specialty modules on pregnancy, mental health, and supporting people experiencing unstable housing.

====2020: Together4Children: [https://www.fosteringhandbook.com/telford/user_controlled_lcms_area/uploaded_files/T4C%20Smoking%20-%20Fostering%20and%20Adoption.pdf Smoking (including use of e-cigarettes) (Fostering, Adoption Special Guardians) Policy and Procedure]====
* “Due to the recognised differences on health impacts, Together4Children treat tobacco smoking and the use of electronic cigarettes differently as reflected in the following policy…Together4Children recognises the low risk to children and does not view the use of ecigarettes as a reason to exclude prospective foster carers/adopters, purely on this basis. However, prospective carer/adopter’s use of e-cigarettes will be discussed at the initial visit, during the full assessment and monitored via the review process. “

====2019: Worcestershire Children First Fostering (WCFF): [https://www.worcestershire.gov.uk/sites/default/files/2022-11/64256_Smoking_and_Vaping_V01.pdf Smoking and E-Cigarettes (Vaping) Policy for Staff and Foster Carers]====
*“Social Workers should support foster carers to give up smoking by signposting them to organisations which can help them…E-cigarettes, also known as vaporisers, are not tobacco cigarettes. The use of them has become more wide spread in recent years and can provide a route for smokers to help them reduce or give up smoking.”

====2018: CoramBAAF: [https://proceduresonline.com/trixcms1/media/2965/corambaafpn68_reducingriskofenvironmentalsmoketolacandcarers.pdf PRACTICE NOTE 68 Reducing the risks of environmental tobacco smoke for looked after children and their carers]====
*“We would strongly recommend that all substitute carers should be proactively encouraged to stop smoking…The issue is therefore not one of banning prospective adopters and new carers, but of engaging with them, providing information and advice, and facilitating access to smoking cessation programmes…"
**Note: Covers us of vapor products

====2014: BAAF: [https://web.archive.org/web/20150317065142/http://www.baaf.org.uk/node/7583 BAAF - British Association for Adoption and Fostering]====
* “Agencies should therefore recognise the low risk to children and not see the use of e-cigarettes as a reason to preclude foster carers or adopters purely on this basis. Each circumstance should be risk assessed on an individual basis.”
**Note: This non-profit closed in 2015 - A new charity called CoramBAAF took its place.

='''Educators'''=

===[https://x.com/mikepesko/status/1363813387961044998 Michael F. Pesko]===
*"(1/Thread): Hey health policy/econ professors, ever considered adding an #ecig section to your health course? Here is a slide deck for you: http://bit.ly/3pCsIGV. Feel free to use any part of this in your own courses to spread knowledge about this important/interesting topic. #econtwitter" (Note: This doc always links to a clickable link for an updated version)

=Suggestions to add to this page=

===2025: [https://link.springer.com/article/10.1007/s11739-025-04131-x Two decades of global tobacco control: time for a rethink]===

Nicotine - Retracted Studies, Papers, and Articles

2026-01-26T09:59:45Z

Skip: /* Retractions by Journal */

[[File:Corrections.png|center|]]
 

<big>'''On this page, we'll explore how mistakes in published works can happen, log commentaries on some published works, and list some examples of retracted papers.'''</big>

=How Mistakes Can Happen=

==Journals==

===2024: (Preprint) [https://www.preprints.org/manuscript/202410.2456/v2 Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy]===
*"This review explores methodological considerations for maximizing the precision and accuracy of observational cohort studies assessing the risk profiles of tobacco and nicotine products. These considerations, informed by the ROBINS framework for minimizing statistical bias, are anchored in a comprehensive characterization of exposure to all tobacco products currently or formerly used, with corroboration of dose-response relationships."
**Citation: Cohen, G., & Cook, S. (2024). Observational Studies of Exposure to Tobacco and Nicotine Products: Best Practices for Maximizing Statistical Precision and Accuracy. Preprints. https://doi.org/10.20944/preprints202410.2456.v2

===2024: [https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1433626/full Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols]===
*"Updating and improving testing standards to incorporate basic conditions of experimental quality is necessary to achieve a more objective evaluation of the risk profile of ECs, which will provide valuable information to all stakeholders (consumers, health professionals, regulators, and the industries themselves)."
**Citation: Sussman RA, Sipala FM, Ronsisvalle S and Soulet S (2024) Analytical methods and experimental quality in studies targeting carbonyls in electronic cigarette aerosols. Front. Chem. 12:1433626. doi: 10.3389/fchem.2024.1433626

===2022: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis]===
*"Studies based on cross-sectional data with no information on age of e-cigarette initiation and age of diagnosis invariably overestimate associations by including cases that were diagnosed before e-cigarette exposure. Although the authors of those studies did not make causal claims in the reports, university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."
**Citation: Rodu B, Plurphanswat N. Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Intern Emerg Med. 2023 Jan;18(1):319-323. doi: 10.1007/s11739-022-03141-3. Epub 2022 Nov 25. PMID: 36434423.
*Commentary: [https://reason.com/wp-content/uploads/2022/12/Polosa-Commentary-IAEM-2022.pdf A tale of flawed e‑cigarette research undetected by defective peer review process]
*Article: [https://reason.com/wp-content/uploads/2022/12/Rodu-Plurphanswat-CrossSec-Studies-IAEM-2022.pdf Diseases That Studies Linked to E-Cigarettes Generally Were Diagnosed Before Subjects Began Vaping]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018638/ Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research]===
*Conclusion: "Our critical appraisal reveals common, preventable flaws, the identification of which may provide guidance to researchers, reviewers, scientific editor, journalists, and policy makers. One striking result of the review is that a large portion of the high-ranking papers came out of US-dominated research institutions whose funders are unsupportive of a tobacco harm reduction agenda..."
**Citation: Hajat C, Stein E, Selya A, Polosa R; CoEHAR study group. Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research. Intern Emerg Med. 2022 Apr;17(3):887-909. doi: 10.1007/s11739-022-02967-1. Epub 2022 Mar 24. Erratum in: Intern Emerg Med. 2022 Aug;17(5):1561. PMID: 35325394; PMCID: PMC9018638.
*Article: [https://filtermag.org/vaping-research-quality/ Researchers Expose the Pitiful Quality of Highly Cited Vaping Studies]

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506048/ A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol]===
*Abstract: "The inhalation of metallic compounds in e-cigarette (EC) aerosol emissions presents legitimate concerns of potential harms for users. We provide a critical review of laboratory studies published after 2017 on metal contents in EC aerosol, focusing on the consistency between their experimental design, real life device usage and appropriate evaluation of exposure risks. All experiments reporting levels above toxicological markers for some metals (e.g., nickel, lead, copper, manganese) exhibited the following experimental flaws: (i) high powered sub-ohm tank devices tested by means of puffing protocols whose airflows and puff volumes are conceived and appropriate for low powered devices; this testing necessarily involves overheating conditions that favor the production of toxicants and generate aerosols that are likely repellent to human users; (ii) miscalculation of exposure levels from experimental outcomes; (iii) pods and tank devices acquired months and years before the experiments, so that corrosion effects cannot be ruled out; (iv) failure to disclose important information on the characteristics of pods and tank devices, on the experimental methodology and on the resulting outcomes, thus hindering the interpretation of results and the possibility of replication"
**Citation: Soulet S, Sussman RA. A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol. Toxics. 2022 Aug 29;10(9):510. doi: 10.3390/toxics10090510. PMID: 36136475; PMCID: PMC9506048.

===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787926/ Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===
*Abstract: "We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and “dry puffs”. The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design."
**Citation: Soulet S, Sussman RA. Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions. Toxics. 2022 Nov 22;10(12):714. doi: 10.3390/toxics10120714. PMID: 36548547; PMCID: PMC9787926.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769337/ Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations]===
*Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context.
**Citation: Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. PMID: 29375395; PMCID: PMC5769337.

===2017: [https://pubmed.ncbi.nlm.nih.gov/28864295/ E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions]===
*The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
**Citation: Farsalinos KE, Voudris V, Spyrou A, Poulas K. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions. Food Chem Toxicol. 2017 Nov;109(Pt 1):90-94. doi: 10.1016/j.fct.2017.08.044. Epub 2017 Aug 31. PMID: 28864295.

===2015: [https://pubmed.ncbi.nlm.nih.gov/25996087/ E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions]===
*Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid.
**Citation: Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. PMID: 25996087.

==Articles/Blogs==

===2024: [https://www.thefirebreak.org/p/formaldehyde-in-vapes-exposing-another Formaldehyde In Vapes? Exposing Another Chemical Scare]===
*"The same can be said of smokers who are discouraged from switching to vapes. In the name of reducing formaldehyde exposure that is already vanishingly small, the anti-vaping warriors have effectively urged people to continue using tobacco products that contain vastly higher quantities of the compound and kill some six million users annually. They manipulate public policy and deprive people–in this case smokers looking to quit–of products that could preserve their health and even save their lives."

===2024: [https://rodutobaccotruth.blogspot.com/2024/04/are-vape-aerosols-really-toxic.html Are Vape Aerosols Really Toxic?]===
*Addresses several studies

=Science Hygiene, the efforts to correct mistakes or seek retractions by experts=
*'''Notes:'''
**'''Dates denote when comments were published, not the paper's publication date.'''
**'''Clicking the link following "Comments RE" takes you to the comment. The article the comment is addressing will be linked under "Referring to."'''

==Addiction / Dependence / Use==
*To learn more about addiction/dependence, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Nicotine_-_Addiction/Dependence Nicotine - Addiction/Dependence]

===2024: Comments RE: [https://pubpeer.com/publications/40A35E1B6BCE23874F886C76971576 E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective]===
*Waa’s “Indigenous perspective” on e‐cigarette policies claiming Māori (the Indigenous people of New Zealand) were being exploited [1] omits some important context... (Lists examples)... Finally, Māori people have diverse views on vaping. For example, the Manager of the National Tobacco Control Advocacy Service, Hapai Te Hauora said in 2019, “Do you know who has a vested interest in vaping? Anyone who is sick of losing 5,000 whānau [family] members a year to tobacco; anyone who acknowledges the growing body of research showing vaping is helping many to break free of their tobacco addiction; anyone who cares about our people”. (Mendelsohn, Glover)
**Referring to: Waa A. E-cigarette policies in Aotearoa (New Zealand): An Indigenous perspective. Addiction. 2024 May 24. Epub ahead of print. PMID: 38794822. [https://onlinelibrary.wiley.com/doi/10.1111/add.16573 doi: 10.1111/add.16573].
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16462 E-cigarettes: A framework for comparative history and policy]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16660 Evidence and policy is certainly more complex than it seems]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16597 A tobacco control policy analysis framework that extends into the future]
***See Also: [https://onlinelibrary.wiley.com/doi/10.1111/add.16577 Adopting the Berridge et al.: Framework to understand differences in the e-cigarette policy between the Nordic countries]

===2024: Comments RE: [https://pubpeer.com/publications/E128EE4F19CD39411FAFDDB6A88FED Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity]===
*Despite the authors correcting recognizing that “no trends… should be inferred” between 2020 and 2021, they infer trends between 2021 and 2022, thus making the very same error, as the artifact relates to NYTS 2021 alone, not 2021 and every year thereafter. (Selya)
**Referring to: Mattingly DT, Hart JL. Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity. JAMA Netw Open. 2024;7(2):e2354872. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814427 doi:10.1001/jamanetworkopen.2023.54872]

===2024: Comments RE: [https://pubpeer.com/publications/DEF986999C6287FCD8FD4048A0B8EE Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022]===
*"Overall, Zhang et al. improperly conclude that there is a true uptick in dual- and poly-use of nicotine and tobacco in NYTS, but did not attribute any of their findings to a well-documented methodological artifact in NYTS 2021 which renders the findings inconclusive, as (in the words of official NYTS publications) 'differences between estimates might be due to changes in methodology, actual behavior, or both.' ” (Selya)
**Referring To: Zhang, B., Bannon, O., Chen, D. T., & Filippidis, F. T. (2024). Dual and poly-nicotine and tobacco use among adolescents in the United States from 2011 to 2022. Addictive Behaviors, 152, 107970. [https://www.sciencedirect.com/science/article/pii/S0306460324000194 https://doi.org/10.1016/j.addbeh.2024.107970]

===2023: Comments RE: [https://pubpeer.com/publications/3BF65B1CBECA15D0EC1068CF8628BC#2 Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth]===
*"Readers may be interested to know that there is now a comment to the Pierce et al paper from Shiffman and Hannon. The commenters raise questions about the conclusions drawn by the original authors and report alternative analyses of the same dataset." (Gitchell)
*"To this last point, Pierce and Strong’s response now reports a relevant analysis, and it directly contradicts their assertion in the original paper: they demonstrate that dependence among JUUL users in each age cohort was not different from dependence in users of other ENDS brands (though the trend is evidently for lower dependence among JUUL users)." (Shiffman)
**Referring To: Pierce JP, Leas EC, Strong DR. Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth. Pediatrics. 2023 Apr 1;151(4):e2022059158. PMID: 36942497. doi: https://doi.org/10.1542/peds.2022-059158

===2022: Comments RE: [https://pubpeer.com/publications/1FF8B75DFC81492DEBC8E214F63098 Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study]===
*A re-analysis of the data by Foxon & Shiffman (2) revealed that those analyses did not include replicate weights as specified in guidance from the PATH study team. Foxon & Shiffman (2) show that when the above analyses are performed with the replicate weights included, the associations above are statistically non-significant. (Foxon, Shiffman)
*(2) [https://www.mdpi.com/1660-4601/20/18/6715 Full Comment]
**Referring to: Wang Y, Duan Z, Weaver SR, Popova L, Spears CA, Ashley DL, Pechacek TF, Eriksen MP, Huang J. Consumption of JUUL vs. Other E-Cigarette Brands among U.S. E-Cigarette Users: Evidence from Wave 5 of the PATH Study. International Journal of Environmental Research and Public Health. 2022; 19(17):10837. [https://doi.org/10.3390/ijerph191710837 https://doi.org/10.3390/ijerph191710837]

===2021: Comments RE: [https://pubpeer.com/publications/57A74561DC4B1B43B91E18A95A24A5 Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users]===
*In summary, by imputing respondents who reported that they “don’t know” which ENDS brand they used to the non-JUUL group even if they may have used JUUL, and by relying on ‘any’ JUUL use definitions which defined as JUUL users those who “usually” used a different ENDS brand, the original analysis systematically biases against the focal brand (JUUL) being studied. (Foxon, Shiffman)
*In summary, the results of Mantey et al. are invalid, because they were based on a definition of JUUL use that is not justified by the brand information in the 2020 National Youth Tobacco Survey.(Rodu)
**Referring to: Mantey DS, Case KR, Omega-Njemnobi O, Springer AE, Kelder SH. Use frequency and symptoms of nicotine dependence among adolescent E-cigarette users: Comparison of JUUL and Non-JUUL users. Drug Alcohol Depend. 2021 Nov 1;228:109078. Epub 2021 Sep 24. PMID: 34614433; PMCID: PMC8595823. [https://doi.org/10.1016/j.drugalcdep.2021.109078 https://doi.org/10.1016/j.drugalcdep.2021.109078]

===2019: Comments RE: [https://pubpeer.com/publications/1F7BA5A2DEC4EF71CA4E7F34C69806 Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys]===
*These (improbable) increases conflict with official data from Statistics Canada that were released shortly after the publication of the paper drawn from the Canadian Community Health Survey, with a representative sample of 65,000. (Bates)
*The Counterfactual: [https://clivebates.com/canada-takes-a-wrong-turn-after-a-flawed-paper-induces-moral-panic-about-youth-vaping-and-smoking/ Canada takes a wrong turn after a flawed paper induces moral panic about youth vaping and smoking]
**Referring to: Hammond D, Reid JL, Rynard VL, Fong GT, Cummings KM, McNeill A, Hitchman S, Thrasher JF, Goniewicz ML, Bansal-Travers M, O'Connor R, Levy D, Borland R, White CM. Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys. BMJ. 2019 Jun 20;365:l2219. Erratum in: BMJ. 2020 Jul 10;370:m2579. PMID: 31221636; PMCID: PMC6582265. [https://doi.org/10.1136/bmj.l2219 doi: 10.1136/bmj.l2219]
**[https://www.bmj.com/content/370/bmj.m2579 Corrections]: "The authors of this paper (BMJ 2019;365:l2219, doi:10.1136/bmj.l2219, published 20 June 2019) have provided an update on estimates of smoking among adolescents and vaping from the ITC Youth and Vaping Surveys conducted in Canada, England, and the United States (see supplementary file for details).
**I note with interest that another paper in BMJ includes the same red-box Correction. However with this one, upon clicking, it opens a page displaying a direct and complete explanation of the correction and a pledge that the paper itself will be updated (it has been). It would be welcome if the journal would apply the same level of rigor to the Hammond et al paper (Gitchell).

===2018: Comments RE: [https://pubpeer.com/publications/58B4D5D27C6A7C45EE3A094D324368 Prevalence and correlates of JUUL use among a national sample of youth and young adults]===
*The results from this article are uninformative, because the authors did not include simple crosstabs of the raw numbers showing the overlap in current use of ENDS, JUUL and combustible products. They failed to denote current ENDS use in the model for Table two. (Rodu)
**Referring to: Vallone DM, Bennett M, Xiao H, Pitzer L, Hair EC. Prevalence and correlates of JUUL use among a national sample of youth and young adults. Tob Control. 2019 Nov;28(6):603-609. Epub 2018 Oct 29. PMID: 30377241. [https://doi.org/10.1136/tobaccocontrol-2018-054693 https://doi.org/10.1136/tobaccocontrol-2018-054693]

===2014: Comments RE: [https://sci-hub.wf/10.1001/jamapediatrics.2014.733 Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents]===
*"In a cross-sectional study, the observed relationship between e-cigarette use and higher and more sustained levels of smoking does not imply causation. Moreover, such studies do not take into account other population characteristics, which may play a crucial role when determining potential causation.2,3 Although the authors acknowledged this limitation in the text, they ended up drawing a conclusion that misleads the public into thinking e-cigarettes are leading to smoking initiation and addiction among adolescents." (Farsalinos, Polosa)
*"Although Dutra and Glantz highlighted an important trend in e-cigarette use among our nation’s youth, failing to consider e-cigarette use in the context of other tobacco products may place undue emphasis on e-cigarettes, overshadowing the importance of the current use of multiple tobacco products as well as experimentation with cigars, smokeless tobacco, and hookah in this population." (Delnevo, Bover Manderski,Giovino)
**Referring to: Dutra LM, Glantz SA. Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. JAMA Pediatr. 2014;168(7):610–617. [https://jamanetwork.com/journals/jamapediatrics/fullarticle/1840772 doi:10.1001/jamapediatrics.2013.5488]

==Cancer==

===2024: Comments RE: [https://pubpeer.com/publications/AC3CFEABA70EC0D0AEBD1568368478 Vaping, Smoking and Lung Cancer Risk]===
*There are 10 issues with this study - Reverse Causality, Combining of Current & Ex-Smokers, Temporal Confounding, Contradiction with National Lung Cancer Trends, Absence of a Dose-Response Relationship, Unclear Definition and Consistency of Use Measures, Recall and Reporting Bias, Biological Implausibility, Uniform Effect Across Histologic Cell Types, Age at smoking initiation not adjusted for. [see commentary for further details] (Herzig)
**Referring to: Bittoni MA, Carbone DP, Harris RE (2024) Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther 9: 10229. https://doi.org/10.29011/2574-710X.10229.

==Cardiovascular==

===2024: Comments RE: [https://pubpeer.com/publications/CD0E2CD6E82EB2F69173F5A1193331#1 Electronic Cigarette Use and Myocardial Infarction]===
*"The research question posed is an important one, since the number of people who have never smoked and who report using e-cigarettes appears to have increased in recent years. However, we are concerned that the methods used in the Alzahrani study [1] make the reported findings highly suspect and the conclusion reached unlikely. This includes: 1) temporality concerns; 2) measurement, diagnosis, and biological plausibility concerns; 3) sample size concerns; 4) model design concerns; and 5) uncareful language." (Foxon, Polosa, Niaura, Cummings, Siegel, Benowitz)
**[https://twitter.com/FloeFoxon/status/1748004148987965469 Tweetorial]
*See also: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055619/ Questionable Effects of Electronic Cigarette Use on Cardiovascular Diseases From the National Health Interview Survey (NHIS, 2014-2021)]
**The study by Alzahrani made erroneous claims and overstated the association between e-cigarettes and myocardial infarction. Our replication shows that the association is driven by age and there were no statistically significant associations with other cardiovascular diseases, coronary heart diseases, and stroke.
***Referring to: Alzahrani T (November 06, 2023) Electronic Cigarette Use and Myocardial Infarction. Cureus 15(11): e48402. [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction doi:10.7759/cureus.48402]

===2022: Comments RE: [https://pubpeer.com/publications/B1574611ED725601C17C3766DB164E Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular disease. A recent analysis by my research group of data from the Population Assessment of Tobacco and Health, which contains this essential temporal information, provides definitive evidence that the results from Osei et al. are deficient and unreliable." (Rodu)
**Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Benjamin EJ, Hall ME, DeFilippis AP, Stokes A, Bhatnagar A, Nasir K, Blaha MJ. Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers. Am J Med. 2019 Aug;132(8):949-954.e2. doi: [https://www.cureus.com/articles/196205-electronic-cigarette-use-and-myocardial-infarction#!/ 10.1016/j.amjmed.2019.02.016]. Epub 2019 Mar 8. PMID: 30853474.

===2022: Comments RE: [https://pubpeer.com/publications/D075EB2EED18CA0311BAC77C783777 Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use]===
*"The study by Vindhyal et al. used the National Health Interview Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
**Referring to: Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS. Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use. Cureus. 2020 Aug 8;12(8):e9618. [https://pubmed.ncbi.nlm.nih.gov/32923219/ doi: 10.7759/cureus.9618]. PMID: 32923219; PMCID: PMC7478662.

===2020: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-smoking-vaping-and-stroke-risk/ Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults]===
*“These findings arise from subgroup analysis involving multiple hypothesis tests and are therefore unreliable. Contrary to the authors’ claim, this study provides no evidence that vaping increases the risk of stroke accrued from smoking tobacco.” (Britton)
*“While the paper itself is careful in interpreting the finding, the press release is grossly misleading. The study provides no justification for the claim that vaping increases the risk of stroke.” (Hajek)
*"While this paper highlights the need to continue studying the potential health effects of e-cigarette use, the results should be interpreted with caution as the observed associations may be simply due to unmeasured confounding and reverse causality.” (Shahab)
**Referring to: Parekh T, Pemmasani S, Desai R. Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults. Am J Prev Med. 2020 Mar;58(3):446-452. [https://pubmed.ncbi.nlm.nih.gov/31924460/ doi: 10.1016/j.amepre.2019.10.008]. Epub 2020 Jan 7. PMID: 31924460.

===2020-2022: Comments RE: [https://pubpeer.com/publications/E4180AE40B2A0F076D7D07CE0B7961 Association Between Electronic Cigarette Use and Myocardial Infarction]===
*Multiple comments:
**"The study by Alzahrani et al. used data from the National Health Interview Survey, which contains no information about when participants started to smoke or vape, and when they were diagnosed with a myocardial infarction." (Rodu)
**"E-cigarettes first appeared in the US at about 2009 and their use picked up from about 2013. In the cohorts from 2014 and 2016 that this study used, most participants with a history of MI can be expected to have had their MI before they tried e-cigarettes...The authors’ conclusions are thus misleading on an important public health issue. The article has been used e.g. to claim that vaping increases risk of cardiovascular disease by the WHO Director Ghebreyesus (DOI: 10.1016/S0140-6736(19)31730-1). The data that the paper reports show no such thing." (Hajek)
*See also: [https://www.ajpmonline.org/article/S0749-3797(21)00290-7/fulltext 2021]
**"Alzahrani and colleagues rightly point out that their models test for and thus demonstrate statistically independent effects of smoking and vaping, but if vaping and smoking are not actually independent contributors to identifying MI occurrence—that is, if the association between e-cigarette use and MI occurrence varies as a function of combustible cigarette use—then the main-effects model cannot be used to draw conclusions about the association between e-cigarette use and MI, independent of (or regardless of) one's history of combustible cigarette use." (Critcher, Siegel)
*See also: [https://sci-hub.wf/10.1016/j.amepre.2019.03.012 2019]
**"As the debate on the risks−benefits of electronic-cigarettes continues, a rigorous evidence base is critical. Although determining whether the use of e-cigarettes carries excess risk for future MI is important, it is not possible through the analysis of cross-sectional data, such as the National Health Interview Survey data, from which temporality cannot be inferred. Equally important, we were unable to replicate the authors’ findings. Given the importance of this topic to public health, we request that the authors provide a full and comprehensive explanation for the discrepancies noted and temper their conclusions about “increased risk of myocardial infarction” to reflect the limitations of cross-sectional data." (Bover Manderski, Singh, Delnevo)
* See also: [https://sci-hub.wf/10.1016/j.amepre.2018.06.007 2018]
**"Of concern,however, is the fact that 95% of EC users were also former or current tobacco cigarette (TC) smokers, and the timing of the MI relative to onset of EC use is unknown. (Middlekauff, Gornbein)
*See also: [https://sci-hub.se/10.1016/j.amepre.2018.11.013 2018]
**"Our findings show the well-established limitations of cross-sectional studies, which cannot justify any claims about causal inference, as mentioned in the conclusion by Alzahrani and colleagues.1 Therefore, the conclusion of their study is incorrect and should be revised." (Farsalinos, Niaura)
***Referring to: Alzahrani T, Pena I, Temesgen N, Glantz SA. [http://Association%20Between%20Electronic%20Cigarette%20Use%20and%20Myocardial%20Infarction Association Between Electronic Cigarette Use and Myocardial Infarction]. Am J Prev Med. 2018 Oct;55(4):455-461. doi: 10.1016/j.amepre.2018.05.004. Epub 2018 Aug 22. Erratum in: Am J Prev Med. 2019 Oct;57(4):579-584. PMID: 30166079; PMCID: PMC6208321.

==Cessation==
To learn more about smoking cessation, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_don%27t_help_people_stop_smoking Myth: Alternative nicotine products don't help people stop smoking]

===2024: Comments RE: [https://www.linkedin.com/posts/jeffrey-l-weiss_publichealth-mondaythoughts-thoughtleadership-activity-7231288859165143042-XOSF?utm_source=combined_share_message&utm_medium=member_desktop Adult Smoking Cessation — United States, 2022]===
*"Concealing important information is not meaningfully different from disseminating falsehoods. Smokers who have been unable or unwilling to quit all use of nicotine with traditional smoking cessation medicines deserve to know that they still have alternatives. It should be unacceptable that the “lead federal agency for comprehensive tobacco prevention and control” would keep potentially life-saving information from them." (Weiss)
***Referring to: VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641. DOI: http://dx.doi.org/10.15585/mmwr.mm7329a1

===2024: Comments RE: [https://pubpeer.com/publications/A21E464F1BA2A64B02D7ABF3A88965 Declines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surge]===
*"However, the authors’ conclusions are based on questionable methodological decisions and flawed analyses. Most notably:
**A. The joinpoint analysis of declining cigarette smoking is incorrectly conducted, in a way that obscures more rapid declines in current cigarette smoking after 2002;
**B. Rather than conducting a standard analysis (i.e., a weighted and adjusted analysis of e-cigarette use and smoking trends), authors instead base their conclusions on tallying states that meet certain ad hoc and stringent criteria for (unadjusted) e-cigarette use and smoking trends; and
**C. Analyses focus on an inappropriately narrow time window that does not fully capture the relevant dynamics. Together these flaws substantially underestimate the degree to which e-cigarettes may have displaced or offset cigarette smoking among youth and young adults.
**Moreover, the conclusion that e-cigarette uptake is independent of the declines in cigarette smoking runs counter to a large and varied body of evidence that e-cigarettes substitute for or displace cigarettes. The authors only discuss two such papers, attempting to undermine their conclusions using some of the same flaws that underlie their own analyses, and neglect to mention the larger body of evidence. Together, this yields an article that could cause readers to hold a distorted view of the available evidence on these important issues." (Selya, Gitchell, Foxon, Sembower, Niaura)
***Referring to: Pierce JP, Luo M, McMenamin SB, et alDeclines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surgeTobacco Control Published Online First: 08 November 2023. [https://tobaccocontrol.bmj.com/content/early/2023/11/08/tc-2022-057907 doi: 10.1136/tc-2022-057907]

===2016-2020: Comments RE: [https://pubpeer.com/publications/E2628F04937D0DBD870E115CB41C8B E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis]===
*Multiple Comments, many linking to more information
**"The most obvious issue is that the result is based on studies that have no bearing on whether e-cigarettes are effective or not. This is because vapers who successfully quit smoking were excluded and only those who failed to do so were retained. The studies were not at fault, they were just not set up to evaluate quit rates in smokers who try and not try vaping. The fault is with misinterpreting their results. The letter in LRM referenced above provides more details." (Hajek)
*[https://www.sciencemediacentre.org/expert-reaction-to-meta-analysis-looking-at-e-cigarette-use-and-smoking-cessation/ Expert Reaction]
**“Publication of this study represents a major failure of the peer review system in this journal.” (West)
**"The current paper represents the latest attempt to bring together the existing literature on e-cigarettes for smoking cessation. While its breadth is to be commended, its conclusions (that e-cigarettes don’t work for smoking cessation) are at best tentative and at worst incorrect. The main reason for this is that attempting to directly compare the results of a body of literature that uses such a wide range of study designs and includes such variable (and often poorly defined) populations and outcomes is difficult, if not impossible. Some of the observational studies included in the review, in particular, suffer from a range of limitations that don’t allow us to reliably assess whether e-cigarettes help smokers quit." (Bauld)
**“Evidence from practice in England shows that two out of three smokers who combined e-cigarettes with additional expert support from a local stop smoking service quit successfully and while dual use is a complex issue, many vapers report using an e-cigarette to cut down and ultimately quit." (O'Connor)
**“This review is grossly misleading in my opinion. There are several problems with the way studies were selected and used, but the main flaw is simple, though not easy to spot. The studies that are presented as showing that vaping does not help people quit only recruited people who were currently smoking and asked them if they used e-cigarettes in the past. This means that people who used e-cigarettes and stopped smoking were excluded. The same approach would show that proven stop-smoking medications do not help or even undermine quitting." (Hajek)
**“This review is not scientific. The information included about two studies that I co-authored is either inaccurate or misleading. In addition, the authors have not included all previous studies they could have done in their meta-analysis. I believe the findings should therefore be dismissed. I am concerned at the huge damage this publication may have – many more smokers may continue smoking and die if they take from this piece of work that all evidence suggests e-cigarettes do not help you quit smoking; that is not the case." (McNeill)
*[https://clivebates.com/who-will-be-duped-by-error-strewn-meta-analysis-of-e-cigarette-studies/ Who will be duped by error-strewn ‘meta-analysis’ of e-cigarette studies?]
**"There are multiple challenges with interpreting the e-cigarette studies routinely appearing in the scientific literature – and over-interpretation is all too easy or even deliberate." (Bates)
*[https://web.archive.org/web/20151026231500/http://truthinitiative.org/sites/default/files/2015.06.30%20E-Cig%20FDA%20Workshop%20Docket%20FINAL.pdf Legacy Foundation (now Truth Initiative) submission to the FDA]
**"While the majority of the studies we reviewed are marred by poor measurement of exposures and unmeasured confounders, many of them have been included in a meta-analysis that claims to show that smokers who use e-cigarettes are less likely to quit smoking compared to those who do not.[73] This meta- analysis simply lumps together the errors of inference from these correlations. As described in detail above, quantitatively synthesizing heterogeneous studies is scientifically inappropriate and the findings of such meta-analyses are therefore invalid."
**"Findings from the studies with the strongest methodologies suggest that e-cigarettes are effective in helping adult smokers to quit or to reduce their cigarette consumption and that rates of smoking cessation with e-cigarettes are similar to rates of cessation with nicotine replacement therapy."
*[https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(16)30024-8.pdf Correspondence]
**"There are other problems—such as selective inclusion of studies, and selective reporting of data from studies that were included —and limitations the authors acknowledge in the text but ignore in their conclusions. Detailed criticism of the methods is, however, not needed, because lumping incongruous studies together—which were mostly not designed to evaluate the efficacy of e-cigarettes, and contain no useful information on this topic unless misinterpreted—makes no scientific sense in the first place." (Hajek, McRobbie, Bullen)
*[https://antithrlies.com/2016/01/17/sunday-science-lesson-what-is-meta-analysis-and-why-was-glantzs-inherently-junk/ Sunday Science Lesson: What is “meta-analysis”? (and why was Glantz’s inherently junk?)]
**"Glantz’s meta-analysis is not just junk science because of details about the studies, though those are problems in themselves. It is junk science because there are probably not even two of the studies in his collection that are similar enough to average together, let alone all of them." (Phillips)
***Referring to: Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016 Feb;4(2):116-28. [https://pubmed.ncbi.nlm.nih.gov/26776875/ doi: 10.1016/S2213-2600(15)00521-4]. Epub 2016 Jan 14. PMID: 26776875; PMCID: PMC4752870.

==COVID==

===2022: Comments RE: [https://pubpeer.com/publications/362B01D2B4E5398302F22585990F19#1 Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review]===
*"It is important to state that there is no empiric evidence of transmission of the SARS-CoV-2 virus or any other pathogen through vaping expirations. None of the sources cited by the authors on this issue (references cited in the first paragraph above) provide such evidence, they merely speculate about it in very vague general terms.
*Given the lack of experimental detection, the potential plausibility and scope of this pathogen transmission should be discussed through well structured models based on the theory and data of pathogen transmission mechanisms. Unfortunately, the authors missed three extensive articles in which we undertook this task (links to the articles). (Sussman)
**Referring to: Singhal S, Degano C, Berenbaum E, Keller-Olaman S. Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review. [https://pubmed.ncbi.nlm.nih.gov/35881057/ J Can Dent Assoc. 2022 Jan;88:m1]. PMID: 35881057.

===2020: Comments RE: [https://pubpeer.com/publications/CEB008BBD48F89272321EB50092793 Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19]===
*Multiple Comments:
**"This article is getting severe criticism on Twitter. This thread summarises one issue and links to threads on other, more classic, problems." (Brown) Further comments by the same author (Brown) point out some errors in tables.
**"The authors surveyed and controlled for socioeconomic factors, ethnicity and compliance with confinement precautions, but not for other risk behaviors besides smoking or vaping (such as alcohol drinking, substance usage, unprotected sex). The lack of this important comparative context further weakens the conclusions of this study." (Sussman)
**"Flaws in the paper itself are only one part of the problem that needs to be addressed by the authors. The other is the public relations offensive mounted on the back of the paper once it was published in the Journal of Adolescent Health on August 11." "Unsurprisingly, such an incendiary claim generated considerable media coverage, even though there is no basis for it in fact or evidence." "Finally, there was a political dimension. On the same day as the article was published, August 11, 2020, Illinois Congressman Raja Krishnamoorthi, Chairman of the Subcommittee on Economic and Consumer Policy, found time to write a press release and letter to the Commissioner of the Food and Drug Administration, Dr. Stephen Hahn demanding FDA "clear the market of e-cigarettes" in response to the study." (Bates)
*See Also:[https://www.qeios.com/read/A58MQC Qeios 1]
**"In this brief peer review, we argue that the data reported by Gaiha et al (https://doi.org/10.1016/j.jadohealth.2020.07.002) regarding associations between vaping and COVID-19 testing are so suspect that any conclusions drawn from it cannot be relied upon. We discuss six main areas of concern and conclude that the paper should be retracted." (Gitchell, Kleykamp, Niaura, Shiffman, Cummings, Sweanor, Abrams)
*[https://www.qeios.com/read/TCEJ7G Qeios 2]
**"In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study." (Farsalinos, Niaura)
***Referring to: Gaiha SM, Cheng J, Halpern-Felsher B. Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19. J Adolesc Health. 2020 Oct;67(4):519-523. [https://www.jahonline.org/article/S1054-139X(20)30399-2/fulltext doi: 10.1016/j.jadohealth.2020.07.002]. Epub 2020 Aug 11. PMID: 32798097; PMCID: PMC7417895.

==Diabetes and Prediabetes==

===2022: Comments RE: [https://pubpeer.com/publications/D3C8E2035BE5C164E9BC19D8D50571 E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey]===
*"The results by Atuegwu et al. are deficient and unreliable, because the authors used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease." (Rodu)
**Referring to: Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM. E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey. Drug Alcohol Depend. 2019 Dec 1;205:107692. [https://pubmed.ncbi.nlm.nih.gov/31707269/ doi: 10.1016/j.drugalcdep.2019.107692]. Epub 2019 Oct 28. PMID: 31707269; PMCID: PMC6893144.

===2022: Comments RE: [https://pubpeer.com/publications/3638F392BE76DCA7CA57ABC8E554BF#1 The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018]===
*"The study by Zhang et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Their results are deficient and unreliable, because a recent analysis by my research group provides definitive evidence that the vast majority of diseases reported by vapers in cross-sectional surveys had been diagnosed before survey participants initiated the behavior." (Rodu)
*2022 Article: [https://www.acsh.org/news/2022/03/08/ignore-headlines-theres-no-science-linking-vaping-prediabetes-16172 Ignore The Headlines: There's No Science Linking Vaping To Prediabetes] (English)
**Limitations of this study include self-report of tobacco use and lack of medical confirmation of prediabetes and other diet information
**BRFSS is a cross-sectional survey, so a causal relationship between E-cigarette use and prediabetes cannot be inferred.
***Referring to: Zhang Z, Jiao Z, Blaha MJ, Osei A, Sidhaye V, Ramanathan M Jr, Biswal S. The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018. Am J Prev Med. 2022 Jun;62(6):872-877. [https://www.ajpmonline.org/article/S0749-3797(22)00024-1/fulltext doi: 10.1016/j.amepre.2021.12.009]. Epub 2022 Mar 3. PMID: 35597566.

==EVALI==

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
**Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Flavors==
*For more information about flavors, please see our page: [https://safernicotine.wiki/mediawiki/index.php/ENDS_Flavors ENDS Flavors]

===2022: [https://pubpeer.com/publications/62DEA1F7805686A6D0172A6B69EFFA Levels of menthol, nicotine and cooling agents measured in JUUL products purchased across a three-year period]===
*The implications made about JUUL products in this study are contradicted by our own contemporaneous and detailed product and manufacturing records and are more readily explained by a methodological artifact that the authors have not fully reported, even after a direct prompt before submitting the manuscript. (Gillman)
**[https://tobaccocontrol.bmj.com/content/33/2/e1 Correction to original paper]
*The PubPeer entry from Juul Labs Inc. (JLI) raises a number of serious questions about this research, the research conduct of the authors, and the editorial practices of the journal. (Bates)
*Referring To: Yassine A, El Hage R, El-Hellani A, et al. Levels of menthol, nicotine, and cooling agents measured in JUUL products purchased across a three-year period Tobacco Control 2022;31:s234-s237. [https://doi.org/10.1136/tc-2022-057506 https://doi.org/10.1136/tc-2022-057506]

===2022: Comments RE: [https://pubpeer.com/publications/053A4DD87764E36C0B9FF00B260480 Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit]===
*This article incorrectly states, “In the wake of the e-cigarette or vaping use-related lung injury (EVALI) outbreak in September 2019, electronic cigarette manufacturer JUUL voluntarily removed flavored pods aside from tobacco and menthol from the U.S. market” That sentence is false and creates a factually inaccurate and damaging link in a reader’s mind between JUUL products and the 2019 lung injuries (EVALI) when none exists. In fact, Juul Labs reduced its flavor portfolio to tobacco and menthol to combat underage use and the ingredients of JUUL products do not include vitamin E compounds or THC that were primarily linked to EVALI. (Murillo)
*Referring to: Silver N, Kucherlapaty P, Kostygina G, Tran H, Feng M, Emery S, Schillo B. Discussions of Flavored ENDS Sales Restrictions: Themes Related to Circumventing Policies on Reddit. Int J Environ Res Public Health. 2022 Jun 23;19(13):7668. PMID: 35805325; PMCID: PMC9266029. [https://doi.org/10.3390/ijerph19137668 doi: 10.3390/ijerph19137668]

==Gateway==
*To learn more about Gateway, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Alternative_nicotine_products_are_a_gateway_to_smoking Myth: Alternative nicotine products are a gateway to smoking]

===2024: Comments RE: [https://pubpeer.com/publications/EAD2B506813B485178822E76F2377F Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey]===
*"Causation vs. association. While the authors are careful in most places to avoid claiming that this association is causal, the authors seem to ultimately conclude in favor of a (causal) gateway hypothesis, which is inappropriate given unmeasured confounding by other “common liability” factors, and the cross-sectional nature of the data." (Selya)
*Referring to: Li S, Zeng X, Di X, Liu S. Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey. Front Public Health. 2024 Jan 15;11:1272680. PMID: 38288432; PMCID: PMC10823011 [https://pubmed.ncbi.nlm.nih.gov/38288432/ doi: 10.3389/fpubh.2023.1272680]

===2022: Comments RE: [https://pubpeer.com/publications/9F3E9313EAE06ED991EE4834D69C8E Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study]===
*"The present re-analysis shows that the report of a gateway effect in the NYTS data by Harrell et al. is not supported by these data when appropriate statistical methodology is applied." (Foxon)
*Referring to: Harrell MB, Mantey DS, Chen B, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Prev Med. 2022 Nov;164:107265. Epub 2022 Sep 22. PMID: 36152819; PMCID: PMC10381788. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381788/ doi: 10.1016/j.ypmed.2022.107265]

===2021: Comments RE: [https://www-sciencemediacenter-de.translate.goog/alle-angebote/research-in-context/details/news/e-zigaretten-als-einstieg-zum-zigarettenrauchen/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en-US Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking]===
*Statements:
*; Prof. Dr. Ute Mons, Head of the Cardiovascular Epidemiology of Aging Working Group, Clinic III for Internal Medicine, Cologne University Hospital : “Since there was no statistical control for possible disruptive factors, a causal interpretation, as it is heard between the lines by the authors, is not justified. It should also be taken into account that the study period ran from 2013 to 2017, but the sale of e-cigarettes to young people in the USA was not banned until 2016.For a long time, e-cigarettes were simply more readily available to young people than conventional cigarettes."
*; Prof. Dr. Daniel Kotz, Professor of Addiction Research and Clinical Epidemiology, Institute for General Practice, University Hospital Düsseldorf : “Overall, there is no clear scientific evidence that e-cigarettes are an entry point into tobacco consumption for adolescents and young adults. It is more likely that a personal basic inclination towards nicotine products and the social environment influence the consumption of e-cigarettes or tobacco independently of one another (so-called common liability theory). International studies show that tobacco smoking is falling among adolescents, even in countries where the consumption of e-cigarettes has increased [2]. This contradicts the so-called gateway theory."
*;Prof. Dr. Heino Stöver, Managing Director of the Institute for Addiction Research Frankfurt (ISFF), Frankfurt University of Applied Sciences : “The study is not suitable for making valid statements about e-cigarettes. The main weak point of the study is that it does not take into account the motives for smoking. According to the current state of research, there is no significant causal relationship between the use of e-cigarettes and subsequent smoking. The research situation points in the opposite direction: The majority of adolescents use e-cigarettes no more than experimenting or occasionally using them. In the future, a research design is required that not only examines correlation but also real causality. Unfortunately, this is still not the case. Not even in this study. Such shortcomings underestimate the great and positive role of the e-cigarette in smoking cessation.With 95 percent fewer pollutants than conventional cigarettes, they are well suited for smokers who want to get rid of their addiction and minimize their risk."
*Refering to: John P. Pierce, Ruifeng Chen, Eric C. Leas, Martha M. White, Sheila Kealey, Matthew D. Stone, Tarik Benmarhnia, Dennis R. Trinidad, David R. Strong, Karen Messer; Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking. Pediatrics February 2021; 147 (2): e2020025122. [https://publications.aap.org/pediatrics/article/147/2/e2020025122/36274/Use-of-E-cigarettes-and-Other-Tobacco-Products-and?autologincheck=redirected 10.1542/peds.2020-025122]

===2018: Comments RE: [https://rodutobaccotruth.blogspot.com/2018/01/tobacco-gateway-report-omits-important.html Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015]===
*The Chaffee article emphasizes odds ratios but omits or obscures important contextual information. While teens who try one tobacco product are more likely to try another, the dominant gateway in the PATH survey was from no previous tobacco use to cigarettes. (Rodu)
*Referring to: Watkins SL, Glantz SA, Chaffee BW. Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015. JAMA Pediatr. 2018;172(2):181–187. [http://doi:10.1001/jamapediatrics.2017.4173 doi:10.1001/jamapediatrics.2017.4173]

===2016: Comments RE: [http://tobaccoanalysis.blogspot.com/2016/06/new-pediatrics-study-provides.html E-Cigarettes and Future Cigarette Use] (#1)===
*The study counted anyone who had even puffed a cigarette once as being a smoker. So theoretically, a subject could have had a single puff of an e-cigarette and hated it, and then had a single puff of a cigarette and hated it, and they would be considered someone who initiated smoking because of vaping first. (Siegel)
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-e-cigarettes-and-future-cigarette-use/ E-Cigarettes and Future Cigarette Use] (#2)===
*Prof. Ann McNeill, Professor of Tobacco Addiction at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London : “The gateway hypothesis in the addictions field is frequently used but is highly contested as it has a poor evidence base in general. This study does nothing to strengthen that evidence base.”
*Prof. Peter Hajek, Director of the Tobacco Dependence Research Unit at Queen Mary University of London : "Like several previous studies of this type, this one just shows that people who try things, try things."
*Referring to: Jessica L. Barrington-Trimis, Robert Urman, Kiros Berhane, Jennifer B. Unger, Tess Boley Cruz, Mary Ann Pentz, Jonathan M. Samet, Adam M. Leventhal, Rob McConnell; E-Cigarettes and Future Cigarette Use. Pediatrics July 2016; 138 (1): e20160379. [http://10.1542/peds.2016-0379 10.1542/peds.2016-0379]

===2016: Comments RE: [https://tobaccoanalysis.blogspot.com/2016/08/new-study-purports-to-show-that-e-cigs.html E-cigarette use is differentially related to smoking onset among lower risk adolescents ]===
*"To be clear, the rest of the story is that this new study provides no evidence that e-cigarettes are a gateway to smoking. Instead, it confirms that actual drug-related risk-taking behavior is a much better predictor of other drug-related risk-taking behavior than simply asking a kid if he thinks he will try another drug in the future or asking a kid how rebellious he is or how much his parents support him."
*"This second problem is that smoking initiation was measured by any experimentation with cigarettes, even if just a puff. So many of the youth in the sample may have puffed on a single e-cigarette at baseline and then puffed on a single cigarette some time over the next year and that would be considered as providing evidence that e-cigarettes are a "gateway" to smoking." (Siegel)
*Referring to: Wills TA, Sargent JD, Gibbons FX, et al E-cigarette use is differentially related to smoking onset among lower risk adolescents [https://tobaccocontrol.bmj.com/content/26/5/534 Tobacco Control 2017;26:534-539].

===2026: Comments RE: Flavored Electronic Cigarette Use and Smoking Among Youth===
*"The problems are obvious to those with any experience in statistics; the paper suffers from recall bias, sampling bias, and drawing causal conclusions from a cross-sectional survey. One of those confounders would be troubling yet the paper contains all of them." ([https://www.acsh.org/news/2016/11/07/all-animals-arent-cows-all-tobacco-isnt-cigarettes-and-surveys-arent-science-10412 Campbell])
*"This is a great example of the widespread bias against e-cigarettes that has taken hold in the tobacco control movement. Instead of presenting the study as showing equivocal results, the investigators and the American Academy of Pediatrics have both "chosen sides." This is not science; it is biased interpretation and presentation of science." ([https://tobaccoanalysis.blogspot.com/2016/11/investigators-botch-interpretation-of.html Siegel])
*Referring to: Hongying Dai, Jianqiang Hao; Flavored Electronic Cigarette Use and Smoking Among Youth. Pediatrics December 2016; 138 (6): e20162513. 10.1542/peds.2016-2513

===2014: Comments RE: [https://tobaccoanalysis.blogspot.com/2014/08/politicians-lie-to-public-about.html Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study]===
*"In a press release issued Monday by 13 members of Congress, a group of politicians claimed that there is "more" evidence that electronic cigarettes are a gateway to smoking...The reference which supports this assertion is a study by Dutra and Glantz which purports to provide data showing that electronic cigarettes are aggravating the tobacco epidemic among youth...The authors of this study make one of the most cardinal errors in all of epidemiology. They ignore the principle that correlation does not equal causation." (Siegel)
*Referring to: Dutra LM, Glantz SA. Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study. JAMA Pediatr. 2014 Jul;168(7):610-7. [http://doi:%2010.1001/jamapediatrics.2013.5488 doi: 10.1001/jamapediatrics.2013.5488]. Erratum in: JAMA Pediatr. 2014 Jul;168(7):684. PMID: 24604023; PMCID: PMC4142115.

==HPHC - Harmful and Potentially Harmful Constituents==

===2024: Comments RE: [https://www.pubpeer.com/publications/2D5B14D827614B6D4EFC821DCD2715 In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting]===
*"As a summary: the study by Beard et al [1] was conducted under such unrealistic conditions that its results (including its cytotoxic analysis) have little relevance to consumers and regulators." (Soulet, Sussman)
*Referring to: Beard JM, Collom C, Liu JY, Obiako P, Strongin RM, Zavala J, Sayes CM. In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting. Toxicology. 2024 Jun 13;506:153865. doi: 10.1016/j.tox.2024.153865. Epub ahead of print. PMID: 38876198.

===2024: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-observational-study-of-lead-and-uranium-levels-in-urine-of-teen-vapers/ Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring]===
*"More important, to me as a statistician at least, is that this research can’t establish that the higher levels of lead and uranium in the urine of participants who said they vaped more often were actually caused by their vaping." (McConway)
*"No control group (i.e., adolescents without any e-cigarette use) was included in the analysis...This study therefore cannot tell us anything about absolute increase in exposure to heavy metals from e-cigarette use in this population, only about relative exposure among less and more frequent e-cigarette users." (Shahab)
*See Also: [https://pubpeer.com/publications/E1834A07BDF105C94CC44DD0815856 PubPeer] "The reported mean values are then consistently far below the limit of detection. To draw any conclusions from values below LOD, is bad practice at best."
*Referring to: Kochvar A, Hao G, Dai HD Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring Tobacco Control Published Online First: 29 April 2024. doi: 10.1136/tc-2023-058554

===2023: Comments RE: [https://pubpeer.com/publications/F7311DC3982D9CD03C060190C9CFCB Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study]===
*The article has several serious shortcomings
**REPRODUCIBILITY AND LACK OF CRUCIAL INFORMATION.
**INAPPROPRIATE AIRFLOW FOR SUB-OHM DEVICES.
**ERRONEOUS CONCENTRATION VALUES
**STORAGE (Sussman)
*Referring to: Tehrani MW, Ahererra AD, Tanda S, Chen R, Borole A, Goessler W, Rule AM. Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study. Journal of Environmental Exposure Assessment. 2023; 2(2): 9. http://dx.doi.org/10.20517/jeea.2023.03

===2022: Comments RE: [https://pubpeer.com/publications/C4BE0346C79DAAC7E1BB2DD6B6FAA3#1 Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence]===
*The reader may find the following commentary on Uguna & Snape by Chris Snowdon of interest. It includes a scientific review of the paper by Roberto Sussman that provides a convincing rebuttal of the author's assertions that heated tobacco products generate smoke. (Bates)
*Referring to: Uguna CN, Snape CE. Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence. ACS Omega. 2022 Jun 22;7(26):22111-22124. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260752/ doi: 10.1021/acsomega.2c01527]. PMID: 35811880; PMCID: PMC9260752.

===2022: Comments RE: [https://pubpeer.com/publications/CF1D17EA015361EED28A7886C21CC1#1 Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors]===
*"Conclusion. This study might be a correct and rigorous examination of various processes of the particulate phase of e-cigarette aerosol that are strictly valid under the abnormal overheating testing conditions. The study does not prove that such processes can occur in low powered devices, or even in high powered devices under the recommended power ranges and airflow rates normally used by consumers. The utility to assess the safety profile of e-cigarettes requires the devices to be tested under the best approximation possible to realistic usage. Unfortunately, this study failed to comply with this important consistency condition." (Sussman)
*Referring to: Dada O, Castillo K, Hogan M, Chalbot MG, Kavouras IG. Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors. Sci Rep. 2022 Nov 3;12(1):18571. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633786/ doi: 10.1038/s41598-022-21798-w]. PMID: 36329089; PMCID: PMC9633786.

===2017: Comments RE: [https://pubpeer.com/publications/6E2711F55673ADF831D636E2D701B9 "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions]===
*Multiple Comments
**"Users will operate the equipment in a way that does not lead to harsh dry puff conditions, with associated high VA formation. This is a key human control feedback that does not exist in laboratory equipment. So experiments that just standardise power settings or volume consumption must take care to validate these are realistic proxies for human use for a particular device. In this paper, many of the coil, power and volume settings combinations were not realistic. That could have been avoided through engaging with people with real practical expertise." (Bates)
**"In reality, as power to the coil increases, liquid consumption also increases. In real-world scenarios, human users regulate both power and liquid flow to minimise the risk of dry-puff conditions and therefore avoiding increases in VA emissions." (Barnes)
*Referring to: Soha Talih, Rola Salman, Nareg Karaoghlanian, Ahmad El-Hellani, Najat Saliba, Thomas Eissenberg, and Alan Shihadeh Chemical Research in Toxicology 2017 30 (10), 1791-1793 [https://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00212 DOI: 10.1021/acs.chemrestox.7b00212]

===2017: Comments RE: [https://pubpeer.com/publications/E5B66481CC847E532FEDB066434E92 Hidden formaldehyde in e-cigarette aerosols]===
*"The problem for the authors is that cancer is a human condition and their calculation is based exposures measured by a lab machine in conditions that no humans would be able to tolerate." (Bates)
*See also: [https://pubpeer.com/publications/5D8FB0EB72850380D1A37DAA2097D6 PubPeer 2015-2017]
**"Although Jensen et al. mentioned in the 2015 NEJM research letter that the health risks of formaldehyde hemiacetal inhalation are unknown ("How formaldehyde-releasing agents behave in the respiratory tract is unknown..."), they made a calculation that the formaldehyde-attributable cancer risk from e-cigarette use is 5 to 15 times higher than from long-term smoking. These two statements are clearly contradictory, and the calculation of any cancer risk from formaldehyde hemiacetal emissions is invalid since no such risk has been established for these compounds." (Farsalinos)
*See also: [https://pubmed.ncbi.nlm.nih.gov/28864295/ replication study]
**"The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided." (Farsalinos, Voudris, Spyrou, Poulas)
*See also 2015: [https://retractionwatch.com/2015/09/11/researchers-call-for-retraction-of-nejm-paper-showing-dangers-of-e-cigarettes/ Researchers call for retraction of NEJM paper showing dangers of e-cigarettes]
**Links to the efforts to have the referenced paper retracted.
*Referring to: Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. [https://www.nejm.org/doi/full/10.1056/nejmc1413069 doi: 10.1056/NEJMc1413069]. PMID: 25607446.

==Marketing / Social Media==

===2019: Comments RE: [https://www.juullabs.com/study-highlights-influence-of-illegal-compatible-products/ Characterising JUUL-related posts on Instagram]===
*A recent study in Tobacco Control relating to an analysis of “JUUL-related” Instagram posts contains serious factual errors and mischaracterizations of JUUL Labs’ historical social-media activity, falsely tying the company to the activities of manufacturers of “JUUL compatible” products that we believe are illegally on the market. (JUUL)
* [https://pubpeer.com/publications/B1DD80F0C868A59D609F0B9699E5F9 Additional comments]: In fact, a completely different story emerges from the data as qualified by Juul's statement. This is that FDA's failure to control newly-introduced Juul look-a-likes (which are illegal if introduced after 8 August 2016) is spawning a lawless industry driven by social media and in conflict with Juul's efforts to control sales of its products to youth. The study does not interrogate the underlying reality and I think Juul is right to react strongly. (Bates)
**Referring to: Czaplicki L, Kostygina G, Kim Y, Perks SN, Szczypka G, Emery SL, Vallone D, Hair EC. Characterising JUUL-related posts on Instagram. Tob Control. 2020 Nov;29(6):612-617. Epub 2019 Jul 2. PMID: 31266903. [https://doi.org/10.1136/tobaccocontrol-2018-054824 doi: 10.1136/tobaccocontrol-2018-054824]

==Multiple Outcomes==

===2024: Comments RE: [https://www.ecigarette-research.org/research/index.php/research/2024/281-ecig-disease Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===
*"The study provides zero evidence on any risk associated with e-cigarette use, whether absolute risk or in comparison with smoking. The question that was supposed to be addressed in this metanalysis CANNOT be examined with the studies included in their analysis." (Farsalinos)
*[https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 See Also]: "The methods look impressive, but the devil is in the dirty details buried in the nearly 100 pages supplemental material. The authors have done an admirable job collecting studies and organizing them, but the conclusions reached are untenable, and unsupportable at least for now." (Cummings)
**Referring to: Glantz SA, Nguyen N, Oliveira da Silva AL. Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes. NEJM Evid. 2024 Mar;3(3):EVIDoa2300229. Epub 2024 Feb 27. PMID: 38411454. [https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300229 doi: 10.1056/EVIDoa2300229]

===2024: Comments RE: [https://tobaccocontrol.bmj.com/content/33/3/373.responses#-comments-on-paper-by-asfar-et-al-%E2%80%9Crisk-and-safety-profile-of-electronic-nicotine-delivery-systems-ends-an-umbrella-review-to-inform-ends-health-communication-strategies%E2%80%9D Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies]===
*"Communicating health risk information about ENDS has to have some context to be meaningful to consumers. A common misconception about tobacco use is that the most dangerous component of the product is nicotine. However, while nicotine can be addictive, it is the other toxicants in tobacco, especially burned tobacco, that are the true culprits of tobacco-related diseases. Thus, when communicating information about the health risks of tobacco products, it makes sense to provide consumers with information about the relative health dangers from burned compared to unburned tobacco products. The example risk messages included in the supplementary materials to the paper appear to be developed with a goal of discouraging anyone from using a vaping product rather than to inform potential users about risks." (Cummings, Smith, Schroeder, Warner, McNeill, Hartmann-Boyce, Levy)
**Referring to: Asfar T, Jebai R, Li W, Oluwole OJ, Ferdous T, Gautam P, Schmidt M, Noar SM, Lindblom EN, Eissenberg T, Bursac Z, Vallone D, Maziak W. Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies. Tob Control. 2022 Sep 8:tobaccocontrol-2022-057495. doi: [https://tobaccocontrol.bmj.com/content/33/3/373 10.1136/tc-2022-057495]. Epub ahead of print. PMID: 36252567; PMCID: PMC10043882.

===2022: Comments RE: [https://colinmendelsohn.com.au/wp-content/uploads/2022/07/Mendelsohn-Wodak-Hall-Borland.-A-critical-analysis-of-Ecigs-and-health-outcomes-systematic-review-of-global-evidence.-DAR-2022.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]===
*Contrary to the conclusions of the Banks review, the evidence suggests that vaping nicotine is an effective smoking cessation aid; that vaping is substantially less harmful than smoking tobacco; that vaping is diverting young people away from smoking; and that vaping by smokers is likely to have a major net public health benefit if widely available to adult Australian smokers. (Mendelsohn)
**Referring to: Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. [https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf Electronic cigarettes and health outcomes: systematic review of global evidence]. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022.

===2022: Comments RE: [https://pubpeer.com/publications/727EA7B64FB27270F20717729D7629 Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice]===
*Although this new research from Moshensky et al., does add to the scientific literature about previously marketed JUUL products, we believe the conclusions presented in the manuscript are not adequately supported by the study data. In addition, the lack of quantitative data on actual dosing limits the ability to establish relevance to potential human exposures from product use. Furthermore, the lack of a comparison against the effects of tobacco smoke limits the ability to evaluate these study findings in the context of the tobacco product risk continuum, and risk relative to use of combusted cigarettes. (Weil)
**Referring to: Moshensky A, Brand CS, Alhaddad H, Shin J, Masso-Silva JA, Advani I, Gunge D, Sharma A, Mehta S, Jahan A, Nilaad S, Olay J, Gu W, Simonson T, Almarghalani D, Pham J, Perera S, Park K, Al-Kolla R, Moon H, Das S, Byun MK, Shah Z, Sari Y, Heller Brown J, Crotty Alexander LE. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife. 2022 Apr 12;11:e67621. PMID: 35411847; PMCID: PMC9005188. [https://doi.org/10.7554/elife.67621 doi: 10.7554/eLife.67621]

===2018: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-modelling-study-on-electronic-cigarettes-in-the-us/ Quantifying population-level health benefits and harms of e-cigarette use in the United States]===
*"The authors make some very speculative assumptions here, particularly on the ‘gateway’ effect in teenagers – they assume that vaping leads to smoking. The trouble is, all their data on this comes from studies that don’t prove anything of the sort...The authors’ estimate of ‘life years lost’ is primarily driven by their overestimate of e-cig use contributing to a significant increase in the uptake of smoking in kids." (Shahab)
*"This new ‘finding’ is based on the bizarre assumption that for every one smoker who uses e-cigs to quit, 80 non-smokers will try e-cigs and take up smoking. It flies in the face of available evidence but it is also mathematically impossible." (Hajek)
**Referring to: Soneji SS, Sung HY, Primack BA, Pierce JP, Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS One. 2018 Mar 14;13(3):e0193328. [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193328 doi: 10.1371/journal.pone.0193328]. PMID: 29538396; PMCID: PMC5851558.

==Respiratory==
*To learn more about Popcorn Lung, please see our page: [https://safernicotine.wiki/mediawiki/index.php/Myth:_Vaping_causes_Popcorn_Lung Myth: Vaping causes Popcorn Lung]

===2023: Comments RE: [https://pubpeer.com/publications/035039E269389CBFC88FCB9AFD225C#8 E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring]===
*Given all these shortcomings (opaqueness, unrealistic airflow and nicotine, likely overexposure of mice), the results of this study are not reliable to assess potential harms from exposure to e-cigarette aerosol. (Sussman)
*Referring to: Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, Miller RA, Wold LE, Gorr MW. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L676-L682. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722245/ doi: 10.1152/ajplung.00233.2022]. Epub 2022 Oct 11. PMID: 36218276; PMCID: PMC9722245.

===2022: Comments RE: [https://pubpeer.com/publications/D93498039BF8D05DFAE58BFC29DD1B The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017]===
*"The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Therefore, it is deficient and unreliable." (Rodu)
*Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019 Oct 16;19(1):180. [https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0950-3 doi: 10.1186/s12890-019-0950-3]. PMID: 31619218; PMCID: PMC6796489.

===2022: Comments RE: [https://pubpeer.com/publications/075B90E6B4FEB1AF3BB188690C317F Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017]===
*"The study by Osei et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Osei, A. D., Mirbolouk, M., Orimoloye, O. A., Dzaye, O., Uddin, S. M. I., Benjamin, E. J., Hall, M.E., DeFilippis, A.P., Bhatnagar, A., Biswal, S.S., Blaha, M. J. (2020). Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017. American Journal of Preventive Medicine. [https://www.ajpmonline.org/article/S0749-3797(19)30479-9/fulltext https://doi.org/10.1016/j.amepre.2019.10.014]

===2022: Comments RE: [https://pubpeer.com/publications/8993443E1BA20DF0D8F4E1F51DFB79 Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data]===
*"The study by Wills et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
*Referring to: Wills TA, Choi K, Pokhrel P, Pagano I. Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data. Prev Med. 2022 Aug;161:107137. [https://www.sciencedirect.com/science/article/abs/pii/S0091743522001864 doi: 10.1016/j.ypmed.2022.107137]. Epub 2022 Jul 9. PMID: 35820496; PMCID: PMC9328844.

===2022: Comments RE: [https://pubpeer.com/publications/7B80EB6A718B6A0F2B4634DFE56886 E-cigarette use and respiratory disorder in an adult sample]===
*"Their study used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
*Referring to: Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019 Jan 1;194:363-370. [https://www.sciencedirect.com/science/article/abs/pii/S0376871618307622 doi: 10.1016/j.drugalcdep.2018.10.004]. Epub 2018 Nov 7. PMID: 30472577; PMCID: PMC6312492.

===2022: Comments RE: [https://pubpeer.com/publications/9946B2A97F6F6AF0F898D95F7CB23D E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report]===
*"The problem with these studies is disentangling the effects of a smoking career (something more complicated than adjusting for current-, former-, never-smoking status) and subsequent vaping behaviour. Also, the relationships are complicated by reverse causation (was the vaping a response to smoking-induced respiratory symptoms?), a hard-to-define counterfactual (has the vaping displaced smoking or displaced abstinence?), and the fact that respiratory damage arises from cumulative exposure and vaping exposures may be adding incremental risk (would the subject have any symptoms if they hadn't smoked first?)." (Bates)
*Referring to: Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 Dec 1;17(12):e0269760. [https://pubmed.ncbi.nlm.nih.gov/36454742/ doi: 10.1371/journal.pone.0269760]. PMID: 36454742; PMCID: PMC9714717.

===2020: Comments RE: [https://pubpeer.com/publications/EF05B531214379DD314797A20F2D9D Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?]===
*"The problem is that vegetable glycerin (glycerol) is not a lipid it is an alcohol. It cannot cause the lipoid pneumonia symptoms mentioned." (Bates)
*"Endogenous lipoid pneumonia from VG (or PG) inhalation is a speculation and implausible...The experience in the US over the past several months clearly shows that the culprit for the acute lung intoxication cases are black market THC oils which were sold as THC oils, not e-cigarette products." (Farsalinos)
*"visual assessment of lung HRCT scans showed no pathological findings in people vaping daily for more than 3.5 years. In particular, no CT features compatible with early signs of COPD (i.e. parenchymal micronodules, ground-glass opacity, or macroscopic emphysema) or lipoid pneumonia or popcorn lung disease were present." (Polosa)
*Referring to: Eissenberg T, Maziak W. Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury? Am J Respir Crit Care Med. 2020 Apr 15;201(8):1012-1013. [https://pubmed.ncbi.nlm.nih.gov/31917600/ doi: 10.1164/rccm.201910-2082LE]. PMID: 31917600; PMCID: PMC7159422.

===2019-2020: Comments RE: [https://pubpeer.com/publications/7571819CEB7A2BC425BE3D7061410D Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis]===
*Multiple Comments:
**"One of the essential criteria of causal inference is that exposure to the cause precedes disease onset. Three of the diseases Glantz studies — COPD, chronic bronchitis and emphysema — take decades to become clinically apparent and would have been present, even though undiagnosed, in many of his cases long before his study began in 2014, and indeed even before e-cigarettes first became available in the US in about 2007. His findings are also flawed by the fact that most vapers have smoked, and since smoking is a strong cause of chronic lung disease, vapers inevitably carry an increased risk of lung disease long after quitting smoking. Glantz claims to have allowed for this statistically but his approach is simplistic: he lacks the detail of lifetime duration and intensity of smoking required. On these grounds alone his conclusion is specious." (Britton)
**"Donald Kenkel and colleagues at Cornell University conducted a replication of the analysis using econometric techniques...When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco." (Bates)
*Referring to: Bhatta DN, Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020 Feb;58(2):182-190. [https://www.ajpmonline.org/article/S0749-3797(19)30391-5/fulltext doi: 10.1016/j.amepre.2019.07.028]. Epub 2019 Dec 16. PMID: 31859175; PMCID: PMC6981012.

===2019: Comments RE: [https://www.sciencemediacentre.org/expert-reaction-to-study-on-ecig-vapour-and-cancer-in-mice/ Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice]===
*Multiple comments:
**“The comparison between mice breathing vapour and mice breathing air is not statistically significant. There is no sample size justification and no power calculation. There is no message to the public here – I suspect these results are just noise.” (Britton)
**“The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures. The authors assigned the effects they observed to a carcinogen NNK – but NNK has been measured before in human vapers, and it is known that exposure from vaping is either negligible or none.” (Hajek)
*Referring to: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. [https://pubmed.ncbi.nlm.nih.gov/31591243/ doi: 10.1073/pnas.1911321116]. Epub 2019 Oct 7. Erratum in: Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22884. PMID: 31591243; PMCID: PMC6815158.

===2017: Comments RE: [https://pubpeer.com/publications/41F6EA57D0803EEE9DF65162DF0097 Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts]===
*"It is literally true that they "find no evidence...", but that is because this study is completely ill-suited to drawing any policy conclusions about e-cigarettes and COPD. Despite hinting at the limitations of cross-sectional data, the authors draw a negative-sounding conclusion without addressing the key question of how respiratory health changes for a given smoker who uses e-cigarettes to quit or cut down once they are ill from smoking or as a way of preventing COPD." (Bates)
*Referring to: Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. [https://pubmed.ncbi.nlm.nih.gov/28884423/ doi: 10.1007/s11606-017-4150-7]. Epub 2017 Sep 7. PMID: 28884423; PMCID: PMC5698219.

===2016: "Popcorn Lung" Comments RE: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892932/ Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes”]===
**"Over the past five years, we have published the results of several studies in which diacetyl and 2,3-pentanedione levels were measured in various consumer products..."
**"..."hundreds of consumer products (e.g., tea, coffee, citrus juices, butter) contain naturally occurring diacetyl and 2,3-pentanedione...several studies have shown that airborne diketones associated with these products are easily detectable..."
**"Unless one assumes that unflavored coffee beans pose a serious risk of “popcorn lung,” a rare and oftentimes lethal disease, then one should agree that exposures to airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk."
**"Similarly, we measured concentrations of naturally occurring diacetyl and 2,3-pentanedione in mainstream cigarette smoke at levels (200–400 ppm and 30–50 ppm, respectively) that are hundreds of thousands of times higher than the NIOSH and ACGIH OELs, yet cigarette smoking is not associated with “popcorn lung”. Also, as others have noted, diketone exposures from traditional cigarettes are higher than those associated with e-cigarette use, hence switching from tobacco to e-cigarettes may result in reduced diketone exposure."
**"Ironically, suggesting that diketone levels in e-cigarettes are potentially dangerous could actually lead to higher diketone exposures in the smoking population if smokers decide not to switch to e-cigarettes due to as yet unfounded health concerns." (Pierce, Abelmann, Finley) For further information, see authors [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892901/ response] to the comments above.
*See Also: 2016: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892907/ On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings]
**"The 51 e-juices sampled make up a very small proportion of all the products sold, and there is variability in the chemical content of specific products as well as how those chemicals are delivered by different devices. The authors therefore acknowledge that it is impossible to extrapolate their results to all the other products on the market. Importantly, this study did not assess levels of diacetyl, 2,3-pentanedione, and acetoin in actual users, much less health effects. So it’s premature to assume that exposure to these chemicals via e-cigarettes causes health problems." (Arnold)
*See Also: 2015: [https://rodutobaccotruth.blogspot.com/2015/12/is-harvard-e-cigarette-buttery-flavor.html Is the Harvard E-Cigarette Buttery Flavor Study Credible?]
**"As I advised previously, vapers should only use liquids that are certified to be free of buttery flavors that are suspected respiratory toxicants. However, laboratory investigations of e-cigarettes should use validated methods to assure credibility. The results of the Harvard Buttery Flavor Study do not meet this standard." (Rodu)
*See Also: 2015: [http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/236-da2 A new study finds diacetyl in e-cigarettes but exaggerates risks and fails to discuss about smoking]
**"In conclusion, the article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes. They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk." (Farsalinos)
*See Also: 2015: [https://tobaccoanalysis.blogspot.com/2015/12/new-study-finds-that-average-diacetyl.html New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking]
**"Nevertheless, it is disingenuous and actually damaging to the public's health to spread the message that vaping causes fatal lung disease or even that it appears to increase the risk for popcorn lung. And it is especially disingenuous and damaging to send these messages to the public without telling us that smoking produces exposure to diacetyl that is on average about 750 times higher than vaping." (Siegel)
*Referring to: Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 2016 Jun;124(6):733-9. [https://pubmed.ncbi.nlm.nih.gov/26642857/ doi: 10.1289/ehp.1510185]. Epub 2015 Dec 8. PMID: 26642857; PMCID: PMC4892929.

===2016: Comments RE: [https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===
*"The mice were severely overdosed with nicotine, up to the lethal levels for mice, and a huge amount above what any human vaper would get...Regarding the relevance to human health, nicotine poisoning poses normally no risk to vapers or smokers because if nicotine concentrations start to rise above their usual moderate levels, there is an advance warning in the form of nausea which makes people stop nicotine intake long before any dangerous levels can accrue. (Mice in these types of experiments do not have that option)." (Hajek)
*Referring to: Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax. 2016 Dec;71(12):1119-1129. [https://pubmed.ncbi.nlm.nih.gov/27558745/ doi: 10.1136/thoraxjnl-2015-208039]. Epub 2016 Aug 24. PMID: 27558745; PMCID: PMC5136722.

===2015: Comments RE: [https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/5dfe1e98-3100-4102-a425-a647b9459456 Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model]===
*" In other words, to obtain the same exposure in humans the e-cig user should take 11000 – 13000 puffs per day. Assuming 8 hours of sleep per day, in order to acquire such a high number of puffs e-cig users would need to take 11-13 puffs per minute and thus practically take an e-cig puff with each breath. In conclusion we recommend that the results of the discussed study should be interpreted with caution and that more studies with more realistic levels of e-liquid exposure should be conducted." (Mukhin, Rose)
*Referring to: Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. (2015) Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. PLoS ONE 10(2): e0116861. https://doi.org/10.1371/journal.pone.0116861

=Retractions by Journal=

===2025: Comments RE: [https://academic.oup.com/ntr/article/28/2/314/8320356 Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review]===
*Therefore, the Editor is retracting this article because the article was accepted with an undisclosed conflict of interest that would have changed the editorial decision.
**Referring to: Xingyu Liu, Rana Tayyarah, Xiang Chang, Xin Gao, Lisha Chen, Critical Appraisal of Animal Studies Assessing Risk of Heated Tobacco Products—A Systematic Review, Nicotine & Tobacco Research, 2025; ntaf189, https://doi.org/10.1093/ntr/ntaf189.

===2024: Comments RE: [https://www.science.org/content/article/questionable-firms-tempt-young-doctors-with-easy-publications Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES]===
*"The more they looked at the article, the more problems they saw. The work was based on data from an annual survey on health and nutrition by the U.S. Centers for Disease Control and Prevention (CDC), but the reported number of survey respondents was inexplicably off by an order of magnitude—the survey is completed by about 5000 people a year, but the paper cited 266,058 respondents from 2015 to 2018. The authors also failed to report whether the difference in age of stroke onset between vapers and traditional smokers could simply be due to vapers being younger overall. And those were just a few of the obvious issues, according to Cohen and Foxon, who alerted both the authors and the journal to their concerns." (Joelving)
*See Also: [https://twitter.com/FloeFoxon/status/1786522387338465755 Tweetorial] (Foxon) and [https://pubpeer.com/publications/1F118DC9A92A4FC13507BB5448462D PubPeer] (Richardson and others - 4 comments)
*Retracted: 18th of December, 2025
**Referring to: Patel U, Patel N, Khurana M, Parulekar A, Patel A, Ortiz JF, Patel R, Urhoghide E, Mistry A, Bhriguvanshi A, et al. Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES. Neurology International. 2022; 14(2):441-452. https://doi.org/10.3390/neurolint14020037

===2022: Original: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239491/ Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study]===
*Citation: RC, Dawoodi S, Fabara SP, Asad M, Khayyat A, Chandramohan S, Aslam A, Unachukwu N, Nasyrlaeva B, Jaiswal R, Chowdary SB, Malik P, Rabbani R. Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study. Gastroenterology Res. 2022 Jun;15(3):113-119. doi: 10.14740/gr1490. Epub 2022 Jun 22. Retraction in: Gastroenterology Res. 2023 Jun;16(3):201. PMID: 35836707; PMCID: PMC9239491.
*2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284643/ Retraction Notice to “Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study”]
**Media - Filter: [https://filtermag.org/vaping-liver-disease-study-retracted/ Journal Retracts Study That Linked Vaping to Liver Disease]

===2022: Original: [https://reason.com/wp-content/uploads/2023/01/1438-9260-6-PB.pdf Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study]===
*Citation: Chidharla A, Agarwal K, Abdelwahed S, Bhandari R, Singh A, Rabbani R, Patel K, Singh P, Mehta D, Manaktala PS, Pillai S, Gupta S, Koritala T. Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study. World J Oncol. 2022 Feb;13(1):20-26. doi: 10.14740/wjon1438. Epub 2022 Feb 8. Retraction in: World J Oncol. 2022 Dec;13(6):417. PMID: 35317331; PMCID: PMC8913014.
*2022: [https://reason.com/wp-content/uploads/2023/01/1562-10357-1-PB.pdf Retraction Notice to “Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study”]
**Media - Reason: [https://reason.com/2023/01/04/a-medical-journal-retracts-a-2022-study-that-linked-vaping-to-cancer/ A Medical Journal Retracts a 2022 Study That Linked Vaping to Cancer]

===2019: Original: [https://www.ahajournals.org/doi/10.1161/JAHA.119.012317 Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]===
**Citation: Bhatta DN, Glantz SA. Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health. J Am Heart Assoc. 2019 Jun 18;8(12):e012317. doi: 10.1161/JAHA.119.012317. Epub 2019 Jun 5. Retraction in: J Am Heart Assoc. 2020 Feb 18;9(4):e014519. Erratum in: J Am Heart Assoc. 2019 Nov 5;8(21):e002313. PMID: 31165662; PMCID: PMC6645634.
*2020: [https://www.ahajournals.org/doi/10.1161/JAHA.119.014519 Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health]
**[https://pubpeer.com/publications/F177153E02CA8B3E7B9E70BC8DB204 PubPeer]
**Media - USA Today: [https://www.usatoday.com/story/news/health/2020/02/20/nyu-scientists-others-call-taxpayer-funded-ucsf-vaping-study-probe/4805323002/ A study claimed vaping doubles risk for heart attacks. It's been retracted for being 'unreliable']

===2019: Original: [https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.29148 Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non–small cell lung cancer]===
**Citation: Liu Z, Lu C, Zhao G, Han X, Dong K, Wang C, Guan JZ, Wang Z. Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non-small cell lung cancer. J Cell Biochem. 2019 Oct;120(10):18370-18377. doi: 10.1002/jcb.29148. Epub 2019 Jun 12. Retraction in: J Cell Biochem. 2024 Apr 5. doi: 10.1002/jcb.30562. PMID: 31190333.
*[https://pubmed.ncbi.nlm.nih.gov/38577886/ PubMed Retraction]
*Retracted 2024: [https://pubpeer.com/publications/D500DE74010B291A7B27CBB9083FEA PubPeer Comment about retraction]

=Retractions by Author Request=

===2025: [https://link.springer.com/article/10.1038/s41388-024-03269-w Retraction Note: Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis]===
"The authors have retracted this article. After publication, concerns were raised regarding highly similar ex vivo brain images in Figs. 2A (Vehicle, right), 5A (miR-4466 inh., left) and 6E (-Nic.+Stat3i, right). The authors thoroughly checked the underlying data and found that the data were mismanaged, which may have affected the presented results.
**Citation: Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R, Singh R, Li W, Topaloglu U, Ruiz J, Watabe K. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022 May;41(22):3079-3092. doi: 10.1038/s41388-022-02322-w. Epub 2022 Apr 23. Retraction in: Oncogene. 2025 Jan 9. doi: 10.1038/s41388-024-03269-w. PMID: 35461327; PMCID: PMC9135627.

===2024: [https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00998-w The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis]===
**Citation: Tehrani, H., Rajabi, A., Ghelichi- Ghojogh, M. et al. RETRACTED ARTICLE: The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis. Arch Public Health 80, 240 (2022). https://doi.org/10.1186/s13690-022-00998-w
*[https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-024-01345-x Retraction Notice]: The authors have retracted this article because it incorrectly reports the results of several studies included in their review. This impacts the overall results of their meta-analysis. The authors have been offered the opportunity to re-analyse their findings and to submit an updated version to the journal, which will be subjected to robust peer review.

===2024: [https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814489 RETRACTED: Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking A Randomized Clinical Trial]===
**Citation: Liu Z. Notice of Retraction: Lin HX et al. Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. 2024 May 1;184(5):589. doi: 10.1001/jamainternmed.2024.1125. PMID: 38551593.
*[https://pubpeer.com/publications/A3736116C180E920966659A2AEA32F Author's retraction request post on PubPeer]
*Retraction Watch: [https://retractionwatch.com/2024/04/02/paper-claiming-vaping-tops-nicotine-gum-for-smoking-cessation-retracted-from-jama-journal/ Paper claiming vaping tops nicotine gum for smoking cessation retracted from JAMA journal]

=Suggestions to add to this page=

===2025: [https://pmc.ncbi.nlm.nih.gov/articles/PMC12708306/ Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey]===

===2024: [https://www.sciencemediacentre.org/expert-reaction-to-epigenetic-changes-in-cells-of-smokers-and-vapers/ expert reaction to epigenetic changes in cells of smokers and vapers]===

===2024: [https://pubpeer.com/publications/9E38A75C420D1F19DA0D48C37FA8D8 Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes]===

===2022: [https://link.springer.com/article/10.1007/s11739-022-03163-x A tale of flawed e-cigarette research undetected by defective peer review process]===
*[https://www.coehar.org/anti-vaping-narrative-driven-by-low-quality-science-goes-undetected-by-editorial-quality-checks/ Anti-vaping narrative driven by low quality science goes undetected by editorial quality checks]

===2022: [https://www.mdpi.com/2305-6304/10/12/714 Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions]===

===2025: [https://www.nature.com/articles/s41467-025-59975-w Retraction Note: Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung]===
*"The authors have retracted this article. After publication, concerns were raised regarding highly similar images in the figures, specifically..."

===2025: RE [https://www.amjmed.com/article/S0002-9343(24)00796-4/fulltext Scientific Inaccuracies in Smoking Cessation Guidance]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://pubpeer.com/publications/566A631490E2222E1E6DE4F44B6989 Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner]===

===2025: RE [https://www.pubpeer.com/publications/B604AE5B635D7A1A0E0A6571FDEF16 Exposure to third hand e-cigarette vapour impairs cognitive function in young mice]===

===2025: [https://www.qeios.com/read/FDX7P3 Exposure to Benzene, Toluene, and Xylenes from Electronic Cigarette Use Compared to Working Environment Permissible Exposure Limits: A Risk Assessment Analysis of a Recent Publication]===

===2025: [https://pubmed.ncbi.nlm.nih.gov/39890471/ The many dangers of e-cigarette misinformation]===

===[https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntae232/7780360?login=false Electronic cigarettes during pregnancy: Another tool for discontinuing smoking?]===
*note: this isn't formatted for placement in the correct section
*[https://x.com/ArielleSelya/status/1839786888099463656 Twitter thread]

===2025: [https://www.qeios.com/read/9XT2GU Critical Appraisal of Exposure Studies on E-Cigarette Aerosols Generated by High-Powered Devices]===
*note: this isn't formatted for placement in the correct section

===[https://pubmed.ncbi.nlm.nih.gov/31712273/ Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes]===
*note: this isn't formatted for placement in the correct section
*[https://www.sciencemediacentre.org/expert-reaction-to-case-study-linking-lung-inflammation-to-vaping-in-a-16-year-old/ Expert Comments]

===Paper: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00253 Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]===
*Comment: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00367 Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]
*Response: [https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00414 Response to Letter to the Editor Regarding Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry]

===Paper: [https://gh.bmj.com/content/9/2/e013866 Pharmaceuticalisation as the tobacco industry’s endgame]===
*Comment: [https://pubpeer.com/publications/374B1C6D333BD84814E878DF9D1611 Title: Errors in one sentence - oversights or indicators of other problems?]

===[https://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/233-pm A new study reports that e-cigarettes emit toxins to the environment but the authors did not really find any…]===

 

[[File:Retracted 2.png|center|]]
[[Category:Studies, Surveys, and Papers]]

Nicotine / THR - Change the Conversation

2026-01-09T11:36:00Z

Skip: /* 2023: 15 Common Logical Fallacies */

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[[File:Nicotine word cloud.jpg|center]]


'''The war to end smoking has turned into the war on nicotine.'''


The focus has been lost, and who the "winners" and "losers" will be has changed. Caught in the middle are consumers who smoke or who used to smoke. AS warring sides try to "win" against the other, the world has forgotten the real "winners" and "losers". '''People who succeed at quitting smoking are the only real winners in this battle. People who die from smoking are the only losers in this fight. This is what we should be concerned about - people who smoke.''' It is time to #ChangeTheConversation. For all sides to sit down and talk real solutions. Work on ways to limit the initiation of smoking (and all age-restricted products) while keeping Safer Nicotine (THR) products on the market for adults who smoke.


We need to listen to the people and orgs below, who have put out the call to '''Change The Conversation'''.

='''Educators'''= 

===2021, Apr 30 - [https://www.frankfurt-university.de/fileadmin/standard/2021-30-04_Prof._Dr._Sto__ver_Stellungnahme_SC_HEER_Report.pdf Statement addressing the Scheer Report by Professor Heino Stöver]=== 


*Via Google Translate: "We can only achieve our ideal of a smoke-free continent if we finally include the harm reduction approach on an equal footing in anti-smoking policy. An open-ended debate would be a first step in the right direction on the EU side and could enable many smokers to switch to less harmful products."

===2020, Aug 10 - [https://academic.oup.com/ntr/article/23/1/36/5890529 Polarization Within the Field of Tobacco and Nicotine Science and its Potential Impact on Trainees]=== 


*Divisive, dominant perspectives on e-cigarettes move the field of nicotine and tobacco science away from scientifically rigorous discourse on this important public health topic, which involves millions of lives at stake. If norms do not change, the polarized climate may pressure trainees to choose or inherit an allegiance towards an uncompromising, one-sided stance. That allegiance can then restrict career development, undermine the credibility of research, and hinder public health progress. There is an urgent need to act to avoid negatively affecting the next generation of nicotine and tobacco research scientists. Though we have suggested some solution-oriented ideas, we are calling for reflection among everyone in the field and particularly among those with influence and power.
*There are important questions that must be addressed, including: (1) as the field continues to conquer a range of research questions on e-cigarettes across a range of disciplines and career levels, how can we work better together toward the shared end goal of eliminating tobacco-related disease and death?; (2) how can scientists who perpetuate polarized viewpoints be incentivized and supported to improve?; (3) to whom can junior scientists turn for help with navigating the polarization in the field?; and (4) how can the academic community avoid contributing to the polarization that seems to pervade the field?

===2020, Apr 23 - [https://pubmed.ncbi.nlm.nih.gov/32335031/ Tobacco harm reduction: Past history, current controversies and a proposed approach for the future]=== 


*To date, more attention has been paid on the virtues or vices of potential harm reduction products such as e-cigarettes with less focus on cigarettes, which prematurely kills half of its long-term consumers. Most in the tobacco control community would agree that an immediate main goal is to rapidly eliminate tobacco-related death and disease. To effectively achieve this goal, a more cohesive and unified approach is urgently needed before million more lives are lost to tobacco use.
*Perhaps this approach could be achieved by convening yet another strategic dialogue on harm reduction that is led by one of the governmental agencies, a scientific organization and/or by respected scientists who are not strongly associated with one particular ideology. At this meeting, the current and evolving science, modeling that projects population health effects under different scenarios, identification of research gaps and consensus on a potential path towards a sensible and agreeable harm minimization approach can be developed. Keeping focus on how best to regulate combusted tobacco products and ANDS and allowing tobacco harm reduction as a component of a comprehensive tobacco control program would be one such approach.

===2018 [https://sci-hub.st/10.1080/09581596.2018.1550252 Caught in the middle: early career researchers, public health and the emotional production of research]=== 


*In this short report, I discuss how public health research, its assessment, and its dissemination outside the academy are produced, in part, through emotional circumstances. Using current debates on e-cigarettes as an example, I show that researchers find themselves uncomfortably positioned in complicated moral and affective landscapes, often making it difficult to represent the nuance of their research.
*Mair and Kierans (2007, p. 109) warned us some time ago that: ‘adopting any normative stance towards tobacco, whether pro- or anti-, would actually interfere with our capacity to document and interpret the significance of tobacco in the lives of those we study’. This statement transfers to the contemporary e-cigarette situation.

='''Lawmakers / Public Officials'''= 

===2021 Mar 23 - [https://manilastandard.net/business/economy-trade/350219/lawmakers-ask-gov-t-to-repeal-unlawful-csc-circular-against-tobacco-companies.html Lawmakers ask gov’t to repeal ‘unlawful’ CSC circular against tobacco companies]=== 


*(Referring to influence from out of country NGO's) "We should not be misdirected by these interest-groups that instead of helping our country in our time of need, work to set us against each other."

='''Tobacco Control / Public Health'''= 

===2022: [https://www.sciencedirect.com/science/article/pii/S2667321522001597 Understanding experts’ conflicting perspectives on tobacco harm reduction and e-cigarettes: An interpretive policy analysis]===
*Our findings indicated that the majority of meanings attached to tobacco harm reduction were rooted in values, ideology, politics, and opinions, rather than straightforward disagreements about the scientific evidence. Respondents had different ideological positions on the War on Drugs, the role of the private sector and the tobacco industry, social justice principles, the inevitability of nicotine use, and the acceptability of addiction. Throughout, experts struggled and disagreed with precisely where and how to define “harm reduction."

===2022: [https://www.healthaffairs.org/doi/10.1377/hlthaff.2022.00187 A Proposed Policy Agenda For Electronic Cigarettes In The US: Product, Price, Place, And Promotion]===
*All members of the public health community should unite to pursue a shared commitment to the principle that both youth and adults deserve a future free of tobacco-related disease.
*Our fondest hope is that the public health community will unite again and fight for a set of policies that, through measured compromise, will both reduce the use of e-cigarettes by youth and increase adult smoking cessation.

===2022: [https://www.medpagetoday.com/opinion/second-opinions/99553 A Bold U.K. Plan to End the Smoking Epidemic]===
*In stark contrast with the consensus of government and public health organizations in those nations, the U.S. is mired in a polarized debate pitting concern regarding the risks of e-cigarettes for youth against their potential to help addicted adult smokers stop smoking.

===2021, Mar 29 [https://www.philanthropy.com/article/vaping-and-philanthropy-debating-strategies-that-work Letters to the Editor (see letter #2): Vaping and Philanthropy: Debating Strategies That Work]=== 


*Written By: Eric N. Lindblom, Senior Scholar, O’Neill Institute for National & Global Health Law, Georgetown University Law Center
*Lindblom was director of the Office of Policy at FDA’s Center for Tobacco Products from 2011 to 2014.
*Mark Gunther’s article on Bloomberg’s funding of efforts to prevent youth e-cigarette use did a good job presenting the current conflicts in the public-health community about e-cigarettes and how best to regulate them. But it did not suggest any ways those conflicts might be resolved or, perhaps, made less important.
*Given the common, overriding goal of reducing tobacco-nicotine deaths and harms as quickly as possible, there are many new tobacco-control policies that all sides of the e-cigarette conflict should be able to agree on and actively support.
*Even those arguing for stronger restrictions on e-cigarettes could at a minimum agree that government tax and price measures should not make e-cigarettes more expensive than smoked tobacco products.
*Another possible consensus antismoking strategy might not raise any significant conflicts, even if it were extended to e-cigarettes (or to all tobacco products). That is requiring that all tobacco products be sold only in adult-only sales outlets.
*To promote switching from smoking to vaping (without any downside risks), even those opposing an e-cigarette harm-reduction approach should also be able to agree that all sales outlets that sell smoked tobacco products should be required to offer e-cigarettes, as well (but not vice versa).

===2021: [https://safernicotine.wiki/mediawiki/index.php/Cliff_Douglas Cliff Douglas] Manifesto: [https://drive.google.com/file/d/1C1nk1XEZ8WhnOXtCGTqHdeqomc9HOuko/view It is Time to Act with Integrity and End the Internecine Warfare Over E-Cigarettes]=== 


*"I urge all of us in the tobacco control community to climb out of the bunker, come to the table, and try to genuinely work together. Stop skirting the truth when it feels inconvenient and open your minds and ears to all of the science that is before us. But the same goes for my other community, with whom I agree regarding the evidence-based promise of THR, but which also bears some responsibility for the adversarial nature of the relationship and for not consistently acknowledging areas of ambiguity or concern, including significant rates of experimentation with vaping by youth and youth-oriented marketing by some segments of the vaping industry. We won’t come together if we don’t come together."

===2021: [https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2021.306416 Balancing Consideration of the Risks and Benefits of E-Cigarettes]===
*The topic of e-cigarettes is controversial. Opponents focus on e-cigarettes’ risks for young people, while supporters emphasize the potential for e-cigarettes to assist smokers in quitting smoking. Most US health organizations, media coverage, and policymakers have focused primarily on risks to youths. Because of their messaging, much of the public—including most smokers—now consider e-cigarette use as dangerous as or more dangerous than smoking.
*The authors are former presidents of the Society for Research on Nicotine and Tobacco (SRNT), the world’s leading professional organization dedicated to the subject. The opinions expressed in this article are solely those of the authors. They do not represent those of SRNT, which has taken no organizational position on the issues discussed in this article and had no involvement in the preparation of this article.

===2021: [https://www.bmj.com/content/361/bmj.k2282.full Polarising the e-cigarette debate confuses people]===
*We read with interest the article on whether the NHS should recommend e-cigarettes. It struck a polarising tone, which we fear will further confuse the public. In an effort to take a sensible position on this divisive issue Sheffield Tobacco Control Board has published an updated [https://smokefreesheffield.org/app/uploads/2021/02/The-Sheffield-TCB-e-cig-policy-statement-Final_2.4-1.pdf consensus statement]. We aim to be a vape-friendly city …

===2021: [https://pubmed.ncbi.nlm.nih.gov/33433588/ Tribes of Trust or Distrust, "Attitude Roots" and Encouraging Scientific Participation in the Tobacco Harm-Reduction Debate]===
*[https://sci-hub.se/10.1093/ntr/ntab006 PDF of full paper]
*Trust reassures, while distrust disqualifies. Battle lines between tobacco harm reduction (THR) supporters and abstinence-only supporters provide an example of more or less trusted or distrusted factions in opposition. Some may think of tobacco control science as an evidence-based, objective, rational scientific citadel. The present account of tribal clashes on THR issues, biased by feelings of trust and mistrust, and arising out of values, moral emotions and attitude roots, seems pertinent to me. That attempts at rational thought are subject to many biasing influences has been recognized for decades...

===2021: [https://tobaccocontrol.bmj.com/content/30/2/119.long Finding ‘common ground’ on shifting sands: observations on the conflicts over product regulation]===
*"The conflicts are real and can be hostile, provoking distress among long-time tobacco control researchers, advocates and observers and exacerbating already-existing philosophical schisms within the tobacco control movement. Hence, there is call for finding common ground, settling on an approach and ceasing the attacks on public health colleagues. Whether this is now (or has ever been) possible is somewhat doubtful, particularly on a global level, and far beyond the scope of an editorial."
 

===2020: [https://drive.google.com/file/d/1CBmxmTeclgKWjA-_7P3GQrddeOkEISIt/view E-Cigarettes, Harm Reduction, and Tobacco Control: A Path Forward?]=== 


*"Consider that in the few minutes it took to review the points in this Commentary, approximately 25 Americans and 300 people worldwide died of complications arising from their use of combusted tobacco. This is a toll that should be unacceptable to all of us, no matter where one stands on the issues presented here. We should not and can not continue to engage in the divisive and shameful conflict that the e-cigarette era has visited upon the tobacco-control community; the lives of too many people are at stake. We can and must do better and move on to the combusted tobacco endgame."

===2019: [https://www.drcherylolson.com/wp-content/uploads/2020/09/Olson_End-the-Tribal-Warfare-12-2019.pdf END THE TRIBAL WARFARE Creating Productive Conversations Between the Vaping Industry and Public Health]===
*The narrative around vaping, initially so full of hope and promise, has taken a wrong turn. Industry and public health people can seem like mistrusting, warring tribes.

===2018: [https://academic.oup.com/ntr/article/21/10/1299/4990310 How to Think—Not Feel—about Tobacco Harm Reduction]=== 


*Taken literally, tobacco harm reduction—reducing the harms created by tobacco—is what everyone in tobacco control wants to accomplish. But, the term “tobacco harm reduction” (THR) has become the source of one of the most divisive, often acrimonious debates in tobacco control history. Intense emotions, on both sides, have obstructed objective consideration of complicated THR issues.
*Participants on both sides of the divisive THR debate need to examine the complicated issues and evidence more objectively. This entails considering both the potential benefits and costs associated with reduced-risk products like e-cigarettes.
*THR can be a complement to, not a substitute for, evidenced-based tobacco control interventions. Tobacco control professionals need to focus on objective assessment of and discussion about the potential costs and benefits of THR.
*Importantly, we need to assess that evidence in a fair and objective manner, and to move forward together toward the elimination of tobacco’s harms. That, after all, is the THR goal shared by every single tobacco control professional.

===2016: [https://www.cspdailynews.com/tobacco/4-takeaways-zellers-nato-show-session Mitch Zeller (FDA/CTP) - The E-Cig Debate Has Been Detrimental to Harm Reduction]=== 


*Zeller went on to discuss the all-too-familiar argument about the potential pros and cons of e-cigs and vaping, wondering if tobacco-control groups and vaping advocates were “having the wrong debate.”
*“The e-cig debate has been emotional, divisive and is not advancing common ground on harm reduction,” he said. “Where and how can we apply the principle of harm reduction to this debate and find common ground? It’s been horribly ineffective to date.
*“Part of the challenge with tobacco-control groups and public-health advocates is a historic distrust of the tobacco industry,” he continued. “Every sector has a role to play (in finding common ground).”

===2016: [https://csnews.com/fdas-zeller-lets-reframe-debate-focus-nicotine FDA's Zeller: Let's Reframe Debate to Focus on Nicotine]=== 


*Explaining this in more depth, the CTP director said "looking at nicotine differently" starts with addressing a few key points:
**Recognize there is a continuum of nicotine-containing products;
**Understand people smoke for the nicotine but die from the tar; and
**Acknowledge the public health opportunity to move tobacco users down the risk spectrum.
*"Are we having the wrong debate? For me, yes. The debate has been about e-cigarettes. It should be about nicotine," he said, adding that "someone needs to step up to the plate" and reframe the debate. Once that is successfully done, the nicotine debate needs to center on some critical questions, according to Zeller. These include: What is the longer-term use for those who need it? Is there a potential need for a period of dual use and, if so, for how long? What are the unintended consequences? Where does the principle of harm reduction come in?

===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959509/pdf/ntv241.pdf A Proposed Collaboration Against Big Tobacco: Common Ground Between the Vaping and Public Health Community in the United States]=== 


*An unfortunate conflict is underway between the public health community and the vaping community over e-cigarettes' harmfulness or lack thereof. This conflict is made worse by an information vacuum that is being filled by vocal members on both sides of the debate. This conflict is avoidable; common ground exists. If both groups rally around what is in their own and the public's best interest-the end of combustible tobacco--all will benefit significantly. If not, the result may be missed opportunities, misguided alliances, and--ultimately-poorer public health.

===2009: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915216/ The Strategic Dialogue on Tobacco Harm Reduction: a vision and blueprint for action in the US]===
*The issues related to tobacco harm reduction continue to challenge the tobacco control research and policy communities.
*For more than 2 years a group of tobacco control researchers, policy and communications experts participated in a process called the Strategic Dialogue on Tobacco Harm Reduction
*The topic of tobacco harm reduction is complex and, at times, contentious. No unified vision or strategy has guided research and policy. No opportunities have existed for individuals with diverse perspectives, such as researchers, policy experts, communications experts and advocates to come together to produce a strategic vision on issues related to this area. Instead, while there is broad support for the need to regulate tobacco products, there has been a fractured and sometimes divisive debate over issues such as the appropriate role of regulation as it relates to harm reduction and, particularly, the roles of smokeless tobacco and nicotine replacement therapy (NRT) in harm reduction.
 

='''Tobacco Harm Reduction'''= 

===2022: [https://filtermag.org/tobacco-control-common-ground/?utm_source=twitter&utm_medium=social&utm_campaign=filter Can the US Tobacco Control Debate Ever Find Common Ground?]===
*With the occasional exception, dialogues about tobacco are dominated by elites—the leaders of [anti-nicotine] advocacy groups, government regulators and academics. Adults who smoke or vape are not often heard, except on Twitter, where they are very active.
*It’s hard to know why the groups that oppose vaping are reluctant to engage with critics. Perhaps it’s because they are mostly winning the debate. They have support in Congress, at the regulatory agencies and at the state and local level. Most Americans now believe, wrongly, that e-cigarettes are just as dangerous or more dangerous than combustible cigarettes. The relentless anti-vaping messaging from the CDC, FDA and the Bloomberg-funded coalition government has been effective.

===2021: Comment by Alex Wodak to blog by Clive Bates: [https://www.clivebates.com/holding-the-bloomberg-anti-vaping-propaganda-complex-to-account/ Holding the Bloomberg anti-vaping propaganda complex to account]=== 


*"If US Government and Taliban can sit down and try to negotiate an end to military activities in Afghanistan then supporters and opponents of tobacco harm reduction should be capable of a polite and respectful discussion to identify and expand common ground. After all, both want to see a worldwide substantial and rapid reduction in smoking related deaths. Need to be carefully planned and have excellent Chair. How about it?"
*[https://www.harmreductionaustralia.org.au/alex-wodak/ Alex Wodak Bio:] "Dr Alex Wodak is a physician who was Director of the Alcohol and Drug Service, St. Vincent’s Hospital, Sydney (1982-2012) but has now retired. Major interests include prevention of HIV among people who inject drugs, prevention of alcohol problems and drug policy reform. Dr. Wodak is President of the Australian Drug Law Reform Foundation and was President of the International Harm Reduction Association (1996-2004). He helped establish the first needle syringe programme and the first supervised injecting centre in Australia when both were pre-legal and often works in developing countries on HIV control among among people who inject drugs. Dr Wodak helped establish the National Drug and Alcohol Research Centre, the Australian Society of HIV Medicine and the NSW Users AIDS Association."

===2020: [https://www.thecommunityagenda.com/index.php?option=com_k2&view=item&id=230:activists-health-workers-call-for-tobacco-harm-reduction&Itemid=174 ACTIVISTS, HEALTH WORKERS CALL FOR TOBACCO HARM REDUCTION]=== 


*"Human rights activists and health workers in Uganda have embarked on a Tobacco Harm Reduction (THR) campaign aimed at reducing or minimizing harm or risks suffered by people and communities as a result of using tobacco products."
*"He stressed that the THR advocacy is not going to fight or conflict with the on going government programs, but to raise an intellectual conversation seeking a deeper understanding of THR and nicotine."

===2018: Joe Gitchell [https://www.youtube.com/watch?v=n1chwTliAyE How to feel AND think about nicotine and those who use it]=== 
*Presentation at the Global Forum on Nicotine


 
===2001: [https://tobaccocontrol.bmj.com/content/10/2/189 Clearing the smoke: the science base for tobacco harm reduction—executive summary]===
*For the purposes of this report, a product is harm reducing if it lowers total tobacco related mortality and morbidity even though use of that product may involve continued exposure to tobacco related toxicants.

===2001: [https://tobaccocontrol.bmj.com/content/10/3/201 Applying the risk/use equilibrium: use medicinal nicotine now for harm reduction]===
*As has been pointed out by others,the current regulatory system is upside down, with the more dangerous products (that is, tobacco products) receiving the least regulation and the least dangerous products (that is, MN) subject to the most stringent constraints.
 

='''Tobacco Industry'''= 

===2022: [https://tobaccoreporter.com/2022/10/03/transformation-and-its-enemies/ Transformation and Its Enemies]===
*But what if there are policies, practices and messages that are good for the tobacco industry and public health? Or bad for both? One of the accusations frequently thrown at public health advocates who favor tobacco harm reduction is that they are doing the bidding of Big Tobacco. No one likes to be accused of that. But implicit in that accusation is either the assumption that tobacco harm reduction cannot be good for both or worse, that it is more important to hurt the tobacco industry than to serve public health.
*In public health, we need to stop our warrior rhetoric and think harder about the world as it really works and what will change it for the better.

===2021: [https://www.qeios.com/read/I3JHRX Finding ‘common ground’ on shifting sands: observations on the conflicts over product regulation]=== 


*Commentary by: Dr. Moira Gilchrist, Vice President Strategic and Scientific Communications and Mr. Antonio Ramazzotti, Vice President Consumer Insights
*We do not speak for the entire tobacco industry, but we do speak for Philip Morris International.
*Businesses—and what they make—change over time because of scientific and technological advancements. In any other sector, it is unthinkable that companies with valuable expertise would be excluded from discussions on the development, commercialization and regulation of innovative technologies that fulfil consumer demand and improve lives.
* There is an alternative to the author’s suggested common ground: listening to the needs, wants and opinions of people who smoke. They are the ultimate decision-makers. They will decide what course of action they want to take, provided they are empowered to do so by science-based regulation.

===2019: [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32126-9/fulltext Philip Morris International: time for a new conversation]=== 


"By demonising a company that is doing exactly as the Editors demand, we might never know exactly how much of an opportunity a tobacco harm-reduction strategy will bring to public health. The only losers if this happens will be the men and women who continue to smoke."
*Written by: Marian Salzman
*[https://www.thelancet.com/action/showPdf?pii=S0140-6736%2819%2932126-9 PDF Version]

='''The Science of Disputes and Negotiations'''= 

===2019: [https://www.arch.virginia.edu/gallery/doc/IEN-Tobacco-THRD-final-digital-singlepages.pdf Civil Dialogue on Tobacco, Nicotine, and Alternative Products Harm Reduction]=== 


*10. Engagement and Dialogue: Encourage Civil Dialogues with Broad Stakeholder Involvement
**There is a need for greater civil engagement between a growing number of stakeholders and experts that includes governmental agencies, public health organizations, tobacco, nicotine and alternative product manufacturers, researchers, consumers, health care professionals, laboratory testing facilities, retailers and wholesalers, and agricultural interests. Engagement should be encouraged in both public and private sector venues.

===[https://read.dukeupress.edu/jhppl/article/42/6/1099/132093/Minors-Moral-Psychology-and-the-Harm-Reduction Minors, Moral Psychology, and the Harm Reduction Debate: The Case of Tobacco and Nicotine]=== 

===[https://sci-hub.se/10.1057/jphp.2009.52 Understanding the origins of anger, contempt, and disgust in public health policy disputes: Applying moral psychology to harm reduction debates]=== 

='''Goals & Tradeoffs'''=

='''Derogatory, Stigmatizing and Racist Language Adds Fuel to the Fire, Doesn't Encourage Meaningful Conversations'''=
*[https://safernicotine.wiki/mediawiki/index.php?title=Nicotine_-_Stigma See Also: Nicotine - Stigma]

==Black Words - Example: Black Market==

===Studies, Papers, Reports===

====2019: [https://www.canada.ca/en/public-health/services/publications/healthy-living/communicating-about-substance-use-compassionate-safe-non-stigmatizing-ways-2019.html Communicating about Substance Use in Compassionate, Safe and Non-Stigmatizing Ways]====
*Instead of "Black Market," use alternative terms such as "illegal supply," "unregulated market," "illegally obtained," "illegally produced," or "diverted."
*“Black” is often used as an adjective to convey that something is illegal or otherwise “bad” (e.g., black market, blacklist, black sheep, blackmail, etc.), which has clear racist underpinnings.

====2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148600/ “Blacklists” and “whitelists”: a salutary warning concerning the prevalence of racist language in discussions of predatory publishing]====
*This commentary addresses the widespread use of racist language in discussions concerning predatory publishing. Examples include terminology such as blacklists, whitelists, and black sheep. The use of such terms does not merely reflect a racist culture, but also serves to legitimize and perpetuate it.
*The racism in such “black is bad, white is good” metaphors is inappropriate and needs to cease.
*...the word WHITENESS has 134 synonyms; 44 of which are favorable and pleasing to contemplate…Only ten synonyms for WHITENESS appear to me have negative implications—and these only in the mildest sense… The word BLACKNESS has 120 synonyms, 60 of which are distinctly unfavorable, and none of them even mildly positive…

===Articles, Blogs, Websites===

====2023: [https://filtermag.org/black-market-cannabis/ Why We Should Abandon the Term “Black Market”]=====

====2021: [https://practicalesg.com/2021/09/say-this-instead-blacklist-blackball-blackmail-black-market-etc/ Say This Instead: “Blacklist,” “Blackball,” “Blackmail,” “Black market,” etc.]====
*"In a continuation of the “Say This Instead” series, let’s look at the pervasive symbolism of “white” as positive and “black” as negative in the English language. Words like “blackmail” (related to extortion), “blackball” (rejection), “blacklist” (banishment), and “black market” (illicitness) are so woven into the fabric of our language that we often don’t reflect on their racist overtones. The meaning of these phrases is always something undesirable. It perpetuates a systemic stigma caused by using the same terms that describe the color of our skin as a delineation between good and bad. Based on our use of these words, “black” is bad and “white” is good."

====2020: [https://www.jdsupra.com/legalnews/racist-language-and-origins-i-didn-t-35616/ Racist Language and Origins I Didn’t Always Know]====
*The symbolism of white as positive and black as negative is pervasive in our culture. ...color is related to extortion (blackmail), disrepute (black mark), rejection (blackball), banishment (blacklist), and illicitness (black market).
*"To be an antiracist means taking action to change inherit bias, implicit bias, systemic racism, covert bias, and micro-aggressions. While we may say things without malice or racist intent, we can do better by learning how to recognize and stop using language with racist origins, meanings, or connotations."

==Grandfathered==

===Articles, Websites, Blogs===

====2022: [https://www.fda.gov/tobacco-products/ctp-newsroom/ctp-updates-grandfathered-tobacco-product-term-pre-existing-tobacco-product CTP Updates “Grandfathered Tobacco Product” Term to “Pre-Existing Tobacco Product”]====
*On Aug. 19, FDA’s Center for Tobacco Products (CTP) updated the term “grandfathered tobacco product” to “pre-existing tobacco product” on all the Center’s systems.
*Additionally, the term “grandfathered” – when used to describe someone or something exempt from a new law or regulation – has its roots in 19th century racist voting laws. Therefore, this terminology has been updated in accordance with CTP’s commitment to diversity, equity, inclusion, and accessibility.

====2013: [https://www.npr.org/sections/codeswitch/2013/10/21/239081586/the-racial-history-of-the-grandfather-clause The Racial History Of The 'Grandfather Clause']====
*"Because of the 15th Amendment, you can't pass laws saying blacks can't vote, which is what they wanted to do," says Eric Foner, a Columbia University historian. "But the 15th Amendment allowed restrictions that were nonracial. This was pretty prima facie a way to allow whites to vote, and not blacks."

==Derogatory Terminology==
*Comment from Skip, the creator of this wiki page:
**Those of us who believe there is a place in the world for alternative nicotine products have witnessed years of stigmatization for people's nicotine use. I encourage all of us to think twice about our own use of stigmatizing words, especially when directed at those we don't agree with. We must remember that we sometimes seem like "zealots" to them, too. Name-calling, disrespectful attitudes, and hurtful words will never open the dialogue between opposing viewpoints. Don't be a PANTZ (pro-alternative nicotine and tobacco zealot).
**Be kind - millions of people are dying from smoking. It is one thing to be enthusiastic, it is another thing to be a rude troll. Show your mission's credibility by treating others respectfully, even if they've come across as rude. We should teach by example.
**Stick with issues, not personal attacks. Many of us did things when we were teens that our parents didn't know about. When it comes to the teen vaping issue, why are we attacking parents? How are they supposed to know what their kids are doing 24/7? With all the misinformation out there, why are we angry at their panic over their child's use of vapor products? Many falsely believe that vaping can kill their kids or turn them into "addicts" (with all the stigma attached to that word). We shouldn't stigmatize parents, call them names, crack jokes about them drinking wine, etc. We should show compassion for their fear and keep offering to have a conversation and work towards solutions.

===Labeling Opponents===
*[https://twitter.com/abraverway/status/1724870868386672868 Video on Twitter]

===ANTZ===
*Anti Nicotine and Tobacco Zealots
*A derogatory label applied to individuals and groups focused on eliminating all nicotine and tobacco products without taking the continuum of risk into consideration. Some of those individuals believe that all forms of nicotine are harmful, and society would experience improved public health without the use of nicotine. Some of those individuals are hyper-focused on concerns about youth initiating nicotine use and struggle to include concerns for anyone who smokes. Much of this debate is focused on e-cigarettes. A good discussion on the lack of balance is in this paper: [https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2021.306416 Balancing Consideration of the Risks and Benefits of E-Cigarettes]

===Bloombuck===
*Term used when referencing Michael Bloomberg, his money, the organizations he financially supports, and his followers.

===Karen===
*A pejorative term for a (most often white) woman (or rarely a man) perceived as entitled or [https://en.wikipedia.org/wiki/Karen_(slang) demanding] beyond the scope of what is reasonable.
*Sometimes called "soccer moms."

===Mass Murderers - Nazi - Homicide===
*Terms used by some pro-tobacco harm reduction advocates aimed towards those whom they don't agree with. Claiming that people who don't support tobacco harm reduction are purposely causing the deaths of people who smoke vs the unintended consequences of certain policies.

===Nanny State or Nanny Stater===
*Nanny State is sexist and pejorative--trying to say that the govt thinks we're all babies in need of a "nanny."
*The term is [https://www.thehindu.com/opinion/op-ed/what-is-nanny-state-in-political-science/article19747473.ece attributed] to British Conservative politician, Iain Macleod, who used it in a derogatory sense to criticize government intervention in people’s lives.
*Example of better terminology: "supporter of state intervention to influence behavior"

===Shill===
*A shill is someone who [https://en.wikipedia.org/wiki/Shill publicly helps] or gives credibility to a person, company, industry, or organization without disclosing their close relationship or employment. In online discussion media, shills make posts expressing opinions that further interests of an organization in which they have a vested interest, such as a commercial vendor or special interest group, while posing as unrelated innocent parties.
*Both sides of the debate tend to aim this slur (without proof) at people they disagree with. Often to accuse someone of working in the tobacco industry or accuse someone of having their pockets lined by a wealthy funder who pushes a specific agenda. It is an attempt to discredit another person.

===Snowflake===
*The phrase is used in a [https://www.bbc.co.uk/programmes/articles/16fXgQp7ymRHF4x8qcrrSq3/from-patriarchy-to-snowflake-five-keywords-you-need-to-know derogatory] way to deride those particularly on the left of the political spectrum, and those with progressive liberal views. The author Chuck Palahniuk used the term 'snowflake' as an insult in his 1996 novel Fight Club. But way back in early 1860s in Missouri, USA, a 'snowflake' was a person who was opposed to the abolition of slavery.

===Tobacco Control =/= People Control===

===Troll===

===Twitterati===
*Califf (FDA)

===Mom's Basement===
*2024: [https://skipscorner.substack.com/p/dr-kings-and-everyones-words-matter Dr. King's #WordsMatter (Yours, too!)]
*[https://twitter.com/bentollphd/status/1631023717688934406 Tweet by SRNT 2023 Atendee]

='''Suggestions to add to this page'''= 

===[https://link.springer.com/article/10.1186/s12889-025-25402-4 Defining a public health approach to substance use: insights from a systematic scoping review and conceptual framework development approach]===

===Latest version of Morven Dialogue===
*and any positive pieces about reaching a consensus, endgame, policy recommendations that are balanced, finding balance, etc.

===2023: [https://www.youtube.com/watch?v=ryTT1ehHnFM 15 Common Logical Fallacies]===

===2023: [https://bigthink.com/the-learning-curve/rapoports-rules-arguments/ Rapoport’s rules: A 4-step strategy to de-escalate tense arguments]===

===2023: [https://www.pnas.org/doi/10.1073/pnas.2301642120 Prosocial motives underlie scientific censorship by scientists: A perspective and research agenda]===

===2023: [https://link.springer.com/chapter/10.1007/978-3-031-23658-7_4 E-Cigarettes and the Burdens of History: Children, Bystanders and the American War on Nicotine]===

===2023: [https://www.politico.eu/article/aggression-ridicule-bullying-inside-the-world-of-e-cigarette-scientists/ Inside the toxic world of vaping scientists ]===

===2023: [https://aimnet.org/elevate-your-leadership-game-a-quick-guide-on-interpersonal-bias/ Elevate Your Leadership Game: A Quick Guide on Interpersonal Bias]===

===2022: [https://www.sciencedirect.com/science/article/pii/S2667321522001597?via%3Dihub Understanding experts’ conflicting perspectives on tobacco harm reduction and e-cigarettes: An interpretive policy analysis]===

===2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680276/ The Past Is Not the Future in Tobacco Control]===
*"We should encourage product innovation and support civil dialogue on issues related to smoking harm reduction."

===2020: [https://ajph.aphapublications.org/doi/10.2105/AJPH.2020.305688 The Harm-Reduction Quandary of Reducing Adult Smoking While Dissuading Youth Initiation]===

===2020: [https://www.emerald.com/insight/content/doi/10.1108/DAT-02-2020-0012/full/html Accelerating an end to smoking: a call to action on the eve of the FCTC’s COP9]===
*Respectful dialogue. The Morven Dialogue has tested the value of multi-player engagement on the many complex issues facing the future of tobacco control. This approach encourages debate and discussion on the issues and minimizes ad hominem attacks or direct harassment of people with different views. Across the sciences, such antagonism is, sadly, far too common and can undermine valuable research. COP participants should condemn this type of behavior and embrace the view of the Wellcome Trust, which deems “bullying and harassment of any kind, in any context, to be unacceptable.”
* [https://www.emerald.com/insight/content/doi/10.1108/DAT-02-2020-0012/full/pdf?title=accelerating-an-end-to-smoking-a-call-to-action-on-the-eve-of-the-fctcs-cop9 PDF of whole paper]

===2020: [https://www.emerald.com/insight/content/doi/10.1108/DAT-04-2020-0022/full/html Perceptions of nicotine in current and former users of tobacco and tobacco harm reduction products from seven countries]===
*An ongoing emotional debate surrounding THR products has so far kept many governments from promoting THR products to lessen the burden of disease caused by tobacco.
*A reason why users of tobacco and THR products around the world find it hard to distinguish between the health risks of smoking and nicotine use may be due to conflicting messages from the media that deviate from the most recent scientific evidence base, overemphasize certain opinions or omit findings that do not align with their readers’ beliefs.
*When examining the media dialogue leading up to the poll, we found that selective coverage was used, sometimes in addition to spreading misleading stories and omitting stories that potentially contradicted a desired message. The conveyed messages seemed to both confirm and strengthen widespread negative beliefs about nicotine. Therapeutic effects and potential beneficial applications of nicotine were completely ignored by the media leading up to the poll despite ongoing research in this field.
*The media could play a decisive role in raising awareness that nicotine is delivered through various products that represent a continuum of risk. Tobacco cessation through THR product use requires a more pragmatic and balanced approach in communications. It remains uncertain how much of the confusion surrounding nicotine can be blamed on inaccurate media messages but this phenomenon has been observed with other topics as well.

===2019: [https://www.coresta.org/abstracts/civil-dialogue-and-engagement-between-diverse-stakeholders-respect-tobacco-harm-reduction Is civil dialogue and engagement between diverse stakeholders with respect to tobacco harm reduction feasible? A review of the past, present and future]===
*The third area will be on whether it is possible in a regulated environment for diverse stakeholders to engage in a civil dialogue that focuses on making harm reduction a legitimate way of significantly reducing disease and death from cigarettes.
[https://safernicotine.wiki/mediawiki/images/c/cc/TSRCArticleSubmission.docx Written Version of presentation]

===2019: [https://ajph.aphapublications.org/doi/10.2105/AJPH.2019.305107 The E-Cigarette Debate: What Counts as Evidence?]===

===2016: [https://www.epicpeople.org/e-cigarette-research/ Taking Sides in E-cigarette Research]===

===2015: [https://nicotinepolicy.net/blogs/guest-blogs/31-scott-balin/123-reliving-history-how-the-tobacco-wars-became-the-vapor-wars Reliving History: How the Tobacco Wars Became the Vapor Wars]===

===2013: [https://journals.sagepub.com/doi/abs/10.1177/009145091304000107 After the Smoke Has Cleared: Reflections from a Former Smoker and Tobacco Researcher]===
*[https://sci-hub.se/10.1177/009145091304000107 Sci-Hub (full paper)]

===2010: [https://sci-hub.st/10.1057/jphp.2009.52 Understanding the origins of anger, contempt, and disgust in public health policy disputes: Applying moral psychology to harm reduction debates]===

===[https://www.scientificamerican.com/article/is-nicotine-all-bad/ Is Nicotine All Bad?]=== 

===[https://sci-hub.se/10.1126/science.aba0032 Evidence, alarm, and the debate over e-cigarettes]=== 

===[https://sloanreview.mit.edu/article/the-problem-with-certainty/ The Problem With Certainty]=== 

===[https://rodutobaccotruth.blogspot.com/2021/07/tobacco-harm-reduction-polar-opposition.html Tobacco Harm Reduction: Polar Opposition Must be Resolved]=== 

===[https://www.mdpi.com/1660-4601/18/11/5560 Tobacco Harm Reduction as a Path to Restore Trust in Tobacco Control]=== 

===[https://twitter.com/INNCOorg/status/1396333154013700097 INNCO tweet about above link]=== 

===[https://pubmed.ncbi.nlm.nih.gov/32086156/ Framing and scientific uncertainty in nicotine vaping product regulation: An examination of competing narratives among health and medical organisations in the UK, Australia and New Zealand]=== 

===[https://drive.google.com/file/d/1tG1X2DDwY7zu4HZYl59ot9qBlJRBfKMy/view Re-thinking nicotine and its effects]=== 


The challenge for policy makers and regulators is to imagine how policy levers, regulations, and other tobacco control
activities can be used in tandem to optimize population health: Preventing youth initiation and escalation, while helping 40
million smokers move to less harmful products and making it easier for them to quit and stay quit.

===2014 [https://www.clivebates.com/memo-to-public-health-grandees-vaping-vapers-and-you/ Memo to public health grandees: vaping, vapers and you]=== 

===2017 [https://fivethirtyeight.com/features/the-easiest-way-to-dismiss-good-science-demand-sound-science/ There’s No Such Thing As ‘Sound Science’]=== 

===2021 [https://www.nature.com/articles/d41586-021-02993-7 Scientists: don’t feed the doubt machine]=== 


[[Category: Associated with TC/PH and THR]]
[[Category:Consumer Advocacy Organization]]
[[Category:Media - Movies, Videos, Vlogs, Blogs, OpEds, News, etc.]]
[[Category: People of note]]
[[Category: Regulations]]
[[Category: THR Advocacy Group]]
[[Category: Tobacco control groups]]
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