Nicotine therapeutic benefits: Difference between revisions

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'''Studies, Surveys, Papers, and Case Studies'''
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*Sometimes it's necessary to view the PDF version to access the full study.
 
*This page is for referencing possible therapeutic (medicinal) '''benefits''' of nicotine.  
<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.'''''</big>
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[[File:Nic Ther Ben.png|alt=Nicotine Therapeutic benefits banner|center]]
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<big>'''Note: Some topics are subgroups under the main topic of "Mental Health." '''</big>
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='''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.
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='''ADD / ADHD / Attention'''=
 
===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.
 
===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://www.academia.edu/18995031/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
*(Note: Need to add summary)
 
===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.
 
===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 (K02MH00981–02) 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.
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='''Addiction / Abuse Liability / Dependence (Nicotine)'''=
 
 
===2021 [https://onlinelibrary.wiley.com/doi/10.1111/add.15403 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use]===
 
*Among US high school students, increases in the prevalence of nicotine product use from 2012 to 2019 do not appear to have been accompanied by a similar increase in the population burden of nicotine dependence. This may be at least partly attributable to a shift in the most common product of choice from cigarettes (on which users are most dependent) to e-cigarettes (on which users are least dependent).
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.15403 PDF Version]
*Citation: Jackson, S. E., Brown, J., and Jarvis, M. J. (2021) Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use. Addiction, 116: 1859– 1870. doi: 10.1111/add.15403
*Acknowledgement: Cancer Research UK (C1417/A22962) supported S.J. andJ.B.’s salaries.
 
===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]===
 
*
 
===2020 [https://www.tandfonline.com/doi/abs/10.1080/10826084.2020.1834582?journalCode=isum20& Dependence and Use Characteristics of Adult JUUL Electronic Cigarette Users]===
 
*
 
===2020 [https://pubmed.ncbi.nlm.nih.gov/33086157/ A comparison of product dependence among cigarette only, ENDS only, and dual users: Findings from Wave 3 (2015-2016) of the PATH study]===
 
*
 
===2020 [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15060 Dependence on e-cigarettes and cigarettes in a cross-sectional study of US adults]===
*
 
===2019 [https://pubmed.ncbi.nlm.nih.gov/31375364/ Changes in E-Cigarette Use Behaviors and Dependence in Long-term E-Cigarette Users]===
*
 
===2018 [https://pubmed.ncbi.nlm.nih.gov/29725702/ Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum]===
 
*These findings are concordant with our previous results and provide evidence that menthol Vuse Solo ECs have abuse liability that is lower than menthol cigarettes and potentially greater than that of nicotine gum.
*[https://sci-hub.se/10.1007/s00213-018-4904-x PDF Version]
*Citation: Stiles MF, Campbell LR, Jin T, Graff DW, Fant RV, Henningfield JE. Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum. Psychopharmacology (Berl). 2018 Jul;235(7):2077-2086. doi: 10.1007/s00213-018-4904-x. Epub 2018 May 3. PMID: 29725702; PMCID: PMC6015619.
*Acknowledgement: ClinicalTrials.gov identifier: NCT02664012. MF Stiles, LR Campbell, and T Jin are full-time employees of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc. DW Graff is a full-time employee of Celerion and provided the original draft of the manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on smoking cessation and tobacco harm minimization (including nicotine replacement therapy and electronic vapor products) to Niconovum, USA, Inc., RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.). JE Henningfield also owns an interest in intellectual property for a novel nicotine medication. Through PinneyAssociates, Fant and Henningfield provide consulting services to pharmaceutical companies on abuse potential assessment, and the regulation of substances with a potential for abuse.
 
===2017 [https://pubmed.ncbi.nlm.nih.gov/28389330/ A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study]===
 
 
*
 
===2015 [https://pubmed.ncbi.nlm.nih.gov/25332459/ Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users]===
 
 
*
 
===2015 [https://pubmed.ncbi.nlm.nih.gov/25561385/ Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes]===
 
 
*
 
===2013 [https://www.federalregister.gov/documents/2013/04/02/2013-07528/modifications-to-labeling-of-nicotine-replacement-therapy-products-for-over-the-counter-human-use Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use]===


==Addiction (Nicotine)==


===2013 [https://www.federalregister.gov/documents/2013/04/02/2013-07528/modifications-to-labeling-of-nicotine-replacement-therapy-products-for-over-the-counter-human-use Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use]===
*We also note that although any nicotine-containing product has the potential to be addicting, based on the available evidence, currently marketed OTC NRT products do not appear to have significant potential for abuse or dependence. A 2010 review of historical reports made to the Agency's Adverse Event Reporting System and to the Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network between 1984 and 2009 suggested that NRT products have a low potential for abuse. Several published studies have also found that the abuse liability and dependence potential of NRT products is low, especially compared to cigarettes.
*We also note that although any nicotine-containing product has the potential to be addicting, based on the available evidence, currently marketed OTC NRT products do not appear to have significant potential for abuse or dependence. A 2010 review of historical reports made to the Agency's Adverse Event Reporting System and to the Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network between 1984 and 2009 suggested that NRT products have a low potential for abuse. Several published studies have also found that the abuse liability and dependence potential of NRT products is low, especially compared to cigarettes.
*[https://www.govinfo.gov/content/pkg/FR-2013-04-02/pdf/2013-07528.pdf PDF Version]
*[https://www.govinfo.gov/content/pkg/FR-2013-04-02/pdf/2013-07528.pdf PDF Version]
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===2012 [https://academic.oup.com/ntr/article-abstract/14/1/75/1047894?redirectedFrom=fulltext Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence]===  
===2012 [https://academic.oup.com/ntr/article-abstract/14/1/75/1047894?redirectedFrom=fulltext Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence]===  
*More recently, it has been found that, although nicotine is the most important addictive component of tobacco smoke, it is probably not the only substance involved in the development of tobacco dependence. In light of what is now known about what determines cigarette smoking, it seems timely to propose a renaming of the [[Abbreviations|'''Fagerstrom Test for Nicotine Dependence (FTND)''']] to the Fagerstrom Test for Cigarette Dependence (FTCD).
 
 
*More recently, it has been found that, although nicotine is the most important addictive component of tobacco smoke, it is probably not the only substance involved in the development of tobacco dependence. In light of what is now known about what determines cigarette smoking, it seems timely to propose a renaming of the [[Special:MyLanguage/Abbreviations|'''Fagerstrom Test for Nicotine Dependence (FTND)''']] to the Fagerstrom Test for Cigarette Dependence (FTCD).
*[https://sci-hub.se/10.1093/ntr/ntr137 PDF Version]
*[https://sci-hub.se/10.1093/ntr/ntr137 PDF Version]
*Citation: Karl Fagerström, Ph.D., Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence, Nicotine & Tobacco Research, Volume 14, Issue 1, January 2012, Pages 75–78, doi: 10.1093/ntr/ntr137
*Citation: Karl Fagerström, Ph.D., Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence, Nicotine & Tobacco Research, Volume 14, Issue 1, January 2012, Pages 75–78, doi: 10.1093/ntr/ntr137
*See Also: 2013: [https://nicotinepolicy.net/blogs/guest-blogs/27-karl-fagerstrom/82-dependence-on-tobacco-and-nicotine Dependence on tobacco and nicotine]
===2003 [https://pubmed.ncbi.nlm.nih.gov/12616334/ Subjective effects of the nicotine lozenge: assessment of abuse liability]===
*Results suggest that the nicotine lozenge has low abuse liability, both in adults and young adults.
*[https://sci-hub.se/10.1007/s00213-002-1361-2 PDF Version]
*Citation: Houtsmuller EJ, Henningfield JE, Stitzer ML. Subjective effects of the nicotine lozenge: assessment of abuse liability. Psychopharmacology (Berl). 2003 Apr;167(1):20-7. doi: 10.1007/s00213-002-1361-2. Epub 2003 Mar 4. PMID: 12616334.
*Acknowledgement: This research was supported by SmithKline Beecham Consumer Healthcare.
===2002 [https://pubmed.ncbi.nlm.nih.gov/12175452/ Flavor improvement does not increase abuse liability of nicotine chewing gum]===
*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).
*[https://sci-hub.se/10.1016/s0091-3057(02)00723-2 PDF Version]
*Citation: Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacol Biochem Behav. 2002 Jun;72(3):559-68. doi: 10.1016/s0091-3057(02)00723-2. PMID: 12175452.
*Acknowledgement: This study was supported by SmithKline Beecham Consumer Healthcare.
<br>


='''Addiction (Nicotine with the use or abuse of recreational substances)'''=


==Addiction (Nicotine with the use or abuse of recreational 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]===  




===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
*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)
*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.
*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.
<br>
='''Allergies / Hayfever / Histamines'''=


==Alzheimer / Dementia / MCI==
===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.
*Acknowledgements: 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).
 
===2009: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614131/?ref=blog.lucy.co Nicotine Primarily Suppresses Lung Th2 but not Goblet Cell and Muscle Cell Responses to Allergens]===
*Animal Study
*These 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: Mishra NC, Rir-Sima-Ah J, Langley RJ, et al. Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol. 2008 Jun 1;180(11):7655-63. doi: 10.4049/jimmunol.180.11.7655. PMID: 18490768; PMCID: PMC2614131.
Acknowledgments: This work was supported in part by grants from the National Institutes of Health (RO1 DA017003, R01 DA04208-15, and RO1DA042087S).
 
===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
<br>


===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]===
='''Alzheimer / Dementia / Mild Cognitive Imparement (MCI)'''=
===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
*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.
*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.
Line 35: Line 233:
*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.
*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]===
===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.  
*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.  
*Safety and tolerability for transdermal nicotine were excellent.  
Line 41: Line 239:
*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.
*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]===
===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.
*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.
*This article examines cognitive decline in the elderly and looks at nicotine's potential role in ameliorating this decline.
Line 49: Line 247:
*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
*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


===2002 [https://pubmed.ncbi.nlm.nih.gov/12436427/ Nicotinic receptors in aging and dementia]===
===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.
*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.
*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.
Line 57: Line 255:
*Keywords: nAChR; neuroprotection; Alzheimer’s disease; Parkinson’s disease; acetylcholine
*Keywords: nAChR; neuroprotection; Alzheimer’s disease; Parkinson’s disease; acetylcholine


===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
*nicotine may have therapeutic uses in the treatment of [[Abbreviations|'''Alzheimer's disease (AD)''']].
*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.
*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]
*[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.
*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]===
===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).  
*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]
*[https://sci-hub.st/10.1007/BF02247426 PDF Version]
Line 69: Line 271:
*Acknowledgements. This research was supported by British-American Tobacco Co. Ltd. BJS thanks the Wellcome Trust and the Eleanor Peel Foundation for support.  
*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]===
===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)
*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]
*[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.
*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.
*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]===
===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.  
*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]
*[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.
*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.
<br>


='''Aphthous ulcers'''=


===2015 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387635/ Use of pure nicotine for the treatment of aphthous ulcers]===


==Aphthous ulcers==
===2015 [https://www.ncbi.nlm.nih.gov/pmc/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.
*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.
*https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387635/?report=printablePrintable Version
*https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387635/?report=printablePrintable Version
*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.
*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.


 
===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]===  
===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.
*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]
*[https://sci-hub.st/10.1016/j.mehy.2011.04.006 PDF Version]
*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  
*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  


 
===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===  
===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===
*NOTE: Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that less people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine.
*NOTE: Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that less people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine.
* 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.
* 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.
Line 103: Line 303:
*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.
*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]===  
===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.
*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)
*[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
*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


 
===1991 [https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1991.tb121180.x?sid=nlm%3Apubmed Recurrent aphthous ulcers and nicotine]===  
===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.
*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]
*[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
*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
<br>


==Arthritis==
='''Arthritis/Skeletal'''=
 
 
==Auditory==


=== 2023: [https://pubmed.ncbi.nlm.nih.gov/36708864/ Tobacco heating system has less impact on bone metabolism than cigarette smoke]===
* We found that, following acute or chronic exposure, particulate matter extract from the aerosol of an HTP, the Tobacco Heating System (THS), was less harmful to the bone coculture system than reference cigarette (1R6F) smoke extract. In the fracture healing model, cultures exposed to the THS extract maintained similar osteoclast activity and calcium deposits as control cultures. Conversely, smoke extract exposure promoted osteoclast activity, resulting in an osteoporotic environment, whose formation could be prevented by bisphosphonate coadministration. Thus, THS is potentially less harmful than cigarette smoke to bone cell differentiation and bone mineralization - both being crucial aspects during the reparative phase of fracture healing.
* Comment From Clive Bates: "A characteristically cautious statement. But still annoying as it gives no sense of the magnitude of "less harmful".  I realise this is not a straightforward idea (see paper), but the harm reduction proposition is necessarily quantitative, even if expressed in pseudo-quantitative terms. If they want the harm reduction proposition to succeed these industries need to develop evidence-based metrics for communicating risk reduction.  Eg. it required xx times the exposure to vape liquids to have the same effect as tobacco smoke."
* Cell/organoid study
* Note: tobacco industry funded (PMI)
* Weng W, Bovard D, Zanetti F, Ehnert S, Braun B, Uynuk-Ool T, Histing T, Hoeng J, Nussler AK, Aspera-Werz RH. Food Chem Toxicol. 2023 Jan 25:113637. doi: 10.1016/j.fct.2023.113637. Online ahead of print. PMID: 36708864


===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]===
= '''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.
*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]
*[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
*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]===  
===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.
*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]
*[https://sci-hub.se/10.1007/s00213-019-05421-x PDF Version]
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*Keywords: Acetylcholinergic systems; Auditory processing; Nicotine; Selective attention; Spectral ripple discrimination; Temporal gap detection; Tone in noise detection.
*Keywords: Acetylcholinergic systems; Auditory processing; Nicotine; Selective attention; Spectral ripple discrimination; Temporal gap detection; Tone in noise detection.


==Autism==
= '''Atopic Dermatitis''' =
 
=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37454697/ Association of Atopic Dermatitis with Substance Use Disorders: A Case-Control Study in the All of Us Research Program.] ===
 
* Joshi TP, Bancroft A, DeLeon D, Garcia D, Kunisetty B, Truong P, Kim SJ. J Am Acad Dermatol. 2023 Jul 14:S0190-9622(23)01361-0. doi: 10.1016/j.jaad.2023.06.051. Online ahead of print. PMID: 37454697 No abstract available.
* Patients with AD, compared to controls, were more likely to use cannabis (4.4% vs 2.7%, 60 P <0.01), hallucinogens (3.2% vs 1.8%, P <0.01), opioids (3.5% vs 1.3%, P <0.01), and 61 stimulants (2.3% vs 1.5%, P <0.01) and less likely to use e-cigarettes (10.8% vs 15.6%, P <0.01) 62 and regular cigarettes (39.0% vs 56.0%, P <0.01).
* In multivariable analysis adjusted for age, 63 income, insurance type, race, sex, depression, and anxiety, only the associations with cannabis 64 (aOR 1.49, 95% CI 1.24-1.80), e-cigarette (aOR 0.71, 95% CI 0.65-0.77), and regular cigarette 65 use (aOR 0.65, 95% CI 0.63-0.68) persisted (Table I)
 
='''Autism'''=
 
=== 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] ===
 
* 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.
* Mouse study, may not explain human response
* Autism Research 2020 Aug;13(8):1311-1334  doi: 10.1002/aur.2342. Epub 2020 Jul 21.


===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]===
===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 [[Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.  
*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.  
*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]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
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*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).
*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).
*Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep
*Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep
<br>


 
='''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]===  
==Behcet's disease==
*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.
 
===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 [[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.
*[https://watermark.silverchair.com/kep401.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAArcwggKzBgkqhkiG9w0BBwagggKkMIICoAIBADCCApkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMAxCHkIQW0BFNu-FbAgEQgIICarldUGOUxaPUQkbU6YWe72wo69i1_IkEjyR5K6ERQb_gEQIwrTl4csqOYUVdLT406p-qMSTS_7zLpVQHWPuJdgRBAfqcybz6DgCy2zqQ5ZosdDgmsw2rhZAzirypCBjNhbMkN7Xkyuzxb5_UBH2oxojOfjOcQnIq2D_0Tvsy5sM69ZomduO1XA9Lc70YNFKCmnXnQNzGDRqHBAGMuu-zgS3TQQOpDGk-5m0zT5i6cuY4jB7MVXhrRYr15XXX5AXbLqbHg9fiHp-qdoZbpD2Xu0Xn5tjlebzDQNOn_kbqPsJLtKXAjLMmtm4zd5VB0nXBqbS-ForIVHIjVDQfOduAnUrfr8mOsLhdwzPl6OV3185qmvVdkZXK_bpp2Xi_xSZrZluc2jZDeITdcrcx7r1pXdtQsxPQvRVP2GaSyFRX1glvIAqfqSnLm6oljfeAR2upPGUoMdDIQimCmjA0nhOdaIyygLJEAFKFpBwZ3jwy0FPtV3rSfjLOhm17_Dx-4BFxNMe1pU9HvnX4_L2EIZND4oAyXZssuI8U8u6DmhIbsj8BeWym5VNIi0yGEVY1I1v48YVnXxLOIMJDpENlFNf0_pNf9BLMuSrk_rPH42Ynok8BJaxD6q0BteLB24hVzQE93HAZzYt6trVdVU2gIRXVTNd47j-w0F8gWnZhOaeAee2uqUjFy5Fb5apSF4LCbxZgc-YX00eats2HuRVBmctlEuoQH28tJIdQ0m_NV7R6l8HqoAOvXvmFUAcEnuKEZ00vm1a6cU6mKwohpZwqt8tBcUCSDTjBM-_4k3b6hCK_kDItfxtcGkG9HkxxzA PDF Version]
*[https://watermark.silverchair.com/kep401.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAArcwggKzBgkqhkiG9w0BBwagggKkMIICoAIBADCCApkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMAxCHkIQW0BFNu-FbAgEQgIICarldUGOUxaPUQkbU6YWe72wo69i1_IkEjyR5K6ERQb_gEQIwrTl4csqOYUVdLT406p-qMSTS_7zLpVQHWPuJdgRBAfqcybz6DgCy2zqQ5ZosdDgmsw2rhZAzirypCBjNhbMkN7Xkyuzxb5_UBH2oxojOfjOcQnIq2D_0Tvsy5sM69ZomduO1XA9Lc70YNFKCmnXnQNzGDRqHBAGMuu-zgS3TQQOpDGk-5m0zT5i6cuY4jB7MVXhrRYr15XXX5AXbLqbHg9fiHp-qdoZbpD2Xu0Xn5tjlebzDQNOn_kbqPsJLtKXAjLMmtm4zd5VB0nXBqbS-ForIVHIjVDQfOduAnUrfr8mOsLhdwzPl6OV3185qmvVdkZXK_bpp2Xi_xSZrZluc2jZDeITdcrcx7r1pXdtQsxPQvRVP2GaSyFRX1glvIAqfqSnLm6oljfeAR2upPGUoMdDIQimCmjA0nhOdaIyygLJEAFKFpBwZ3jwy0FPtV3rSfjLOhm17_Dx-4BFxNMe1pU9HvnX4_L2EIZND4oAyXZssuI8U8u6DmhIbsj8BeWym5VNIi0yGEVY1I1v48YVnXxLOIMJDpENlFNf0_pNf9BLMuSrk_rPH42Ynok8BJaxD6q0BteLB24hVzQE93HAZzYt6trVdVU2gIRXVTNd47j-w0F8gWnZhOaeAee2uqUjFy5Fb5apSF4LCbxZgc-YX00eats2HuRVBmctlEuoQH28tJIdQ0m_NV7R6l8HqoAOvXvmFUAcEnuKEZ00vm1a6cU6mKwohpZwqt8tBcUCSDTjBM-_4k3b6hCK_kDItfxtcGkG9HkxxzA PDF Version]
*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
*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
*Keywords: Behçet’s disease, Cigarette smoking, Nicotine therapy, Mucocutaneous lesions
*Keywords: Behçet’s disease, Cigarette smoking, Nicotine therapy, Mucocutaneous lesions


===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]===
===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.
*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)
*[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
*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
<br>


 
='''Brain Injury / Disease'''=  
 
===2004 [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===  
==Brain Injury / Disease==
 
===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.
*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]
*[https://sci-hub.st/10.1196/annals.1332.019 PDF Version]
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*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.
*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.
*KEYWORDS: nicotine; neurodegeneration; neuroprotection
*KEYWORDS: nicotine; neurodegeneration; neuroprotection
<br>


 
='''Cancer / Cancer Treatments'''=  
 
===2020 [https://www.sciencedirect.com/science/article/abs/pii/S001448272030416X?via%3Dihub Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells]===  
==Cancer / Cancer Treatments==
*Nicotine inhibits ovarian cancer cell ERK and p38 [[Special:MyLanguage/Abbreviations|'''MAPK''']] signaling.
 
===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 [[Abbreviations|'''MAPK''']] signaling.
*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]
*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]
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*Keywords: Nicotine, Ovarian cancer, Spheroid, MAPK, Invasion
*Keywords: Nicotine, Ovarian cancer, Spheroid, MAPK, Invasion


===2013 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===
===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.  
*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.  
*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 [[Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.  
*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]
*[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.
*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.
*Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.
*Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy
*Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy
<br>


 
='''Cannabis / THC'''=  
 
===2020 [https://pubmed.ncbi.nlm.nih.gov/32034447/ Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial]===  
==Cannabis / THC==
*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.
 
===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 [[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]
*[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.
*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.
*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.
*Keywords: Cannabis; Marijuana; Negative affect; Nicotine; Smoking; THC; Testing effect; Withdrawal symptoms.
<br>
='''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
<br>
='''Cognitive / IQ / Memory'''=
=== 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


==Cognitive / IQ==
=== 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


===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]===
===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.
*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]
*[https://sci-hub.se/10.1016/j.neuroscience.2020.07.029 PDF Version]
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*Key words: nicotine, cholinergic, cognitive control, distraction, task switching, neuroimaging
*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]===
===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.  
*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]
*[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.
*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.


===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


===2012: The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition===
===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 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 nicotine content in this respect may be more important for males.
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*[https://sci-hub.se/10.1016/j.addbeh.2012.03.004 PDF Version]
*[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  
*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.  
*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.
 


===2003 [https://www.nature.com/articles/1300202 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects]===
===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.
*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]
*[https://www.nature.com/articles/1300202.pdf PDF Version]
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*Keywords: cholinergic agents, ethanol, cognition, psychomotor performance, psychopharmacology, aerospace medicine
*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]===
===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 ([[Abbreviations|'''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 [[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.
*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]
*[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
*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
*Key words: Intelligence, APM, Nicotine, Smoking Cholinergic system


 
===1992 [https://pubmed.ncbi.nlm.nih.gov/1579636/ Nicotine as a cognitive enhancer]===  
===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 attention in a wide variety of tasks in healthy volunteers.  
*Nicotine improves immediate and longer term memory in healthy volunteers.  
*Nicotine improves immediate and longer term memory in healthy volunteers.  
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*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.
*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.
*Keywords: acetylcholine, Alzheimer's Disease, attention, cholinergic, memory, nicotine, scopolamine.
<br>
='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
=== 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.


==Digestive Tract / Bowel==
=== 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.


===2008 [https://www.hindawi.com/journals/grp/2008/237185/ Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study]===
===2023: [https://www.nature.com/articles/s41598-023-45072-9 Treatment of 95 post-Covid patients with SSRIs]===
*Smoking has a detrimental effect in [[Abbreviations|'''Crohn's disease (CD)''']], but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits [[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.
*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
 
===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'''=
===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.
*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.
*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
 
===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.
*Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
*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
 
===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.
*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]
*[http://downloads.hindawi.com/journals/grp/2008/237185.pdf PDF Version]
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*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.
*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]===
===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.
*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]
*[https://sci-hub.st/https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004722.pub2/full PDF Version]
*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.
*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.


===1999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014383/ Nicotine treatment for ulcerative colitis]===
===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
*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.
*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.
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*Keywords: enemas, nicotine, transdermal patches, ulcerative colitis
*Keywords: enemas, nicotine, transdermal patches, ulcerative colitis


===1996 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398677/ The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.]===
===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.
*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]
*[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.
*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?]===
===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.
*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.
*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.
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*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.
*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]===
===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)
*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]
*[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.
*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.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
<br>


='''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]===  
==Downs Syndrome==
 
===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.  
*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]
*[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.
*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.
*Acknowledgements: We thank Pharmacia-Upjohn, Uppsala, Sweden, for providing transdermal nicotine patches. This study was supported by the Red Bull Company, Salzburg.
<br>


 
='''Endurance / Exercise / Athletic Performance'''=
 
===2006 [https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2006.033373 Effect of transdermal nicotine administration on exercise endurance in men]===  
==Endurance / Exercise / Athletic Performance==
 
===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.
*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]
*[https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2006.033373 PDF Version]
*Mündel, T. and Jones, D.A. (2006), Effect of transdermal nicotine administration on exercise endurance in men. Experimental Physiology, 91: 705-713. doi: 10.1113/expphysiol.2006.033373
*Mündel, T. and Jones, D.A. (2006), Effect of transdermal nicotine administration on exercise endurance in men. Experimental Physiology, 91: 705-713. doi: 10.1113/expphysiol.2006.033373
<br>


='''HIV/AIDS'''=
===2022: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908735/ Tobacco Harm Reduction with Vaporised Nicotine (THRiVe): A Feasibility Trial of Nicotine Vaping Products for Smoking Cessation Among People Living with HIV]===
*This study found that the provision of NVPs for 12 weeks was associated with 7-day point prevalence tobacco smoking abstinence among 35% of a sample of PLHIV who smoked tobacco daily. These findings suggest that NVPs represent a potentially feasible and effective short-to-medium term tobacco smoking cessation aid and/or tobacco harm reduction strategy among PLHIV.
<br>
='''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.
<br>
='''Inflammation'''=


==HIV/AIDS==
===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.


===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.
*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.
*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


==Mental Health - ADD/ADHD==
===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]===
*[https://www.nami.org/About-Mental-Illness/Mental-Health-Conditions/ADHD Attention Deficit Hyperactivity Disorder (ADHD) - Information from NAMI]
*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.
*[https://www.understood.org/en/learning-thinking-differences/child-learning-disabilities/add-adhd/is-adhd-a-mental-illness Is ADHD a mental illness?]
*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).
**Mental illness is a very broad term. It refers to any type of condition that affects a person’s behavior, mood, or thinking.
*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
**Technically a mental illness, few practitioners use the words “mental illness” to describe kids with ADHD. They tend to refer to it as a “behavior disorder.” Some might even refer to it as a learning difference that can affect all areas of learning.
*[https://www.understood.org/en/learning-thinking-differences/child-learning-disabilities/add-adhd/difference-between-add-adhd The difference between ADD and ADHD]


===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.


===2011 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353150/ Cognitive enhancers for the treatment of ADHD]===
===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]===
*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.
*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."
*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: 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.


===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]


===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]===
===2013 [https://journals.asm.org/doi/10.1128/cvi.00636-12 Targeting the “Cytokine Storm” for Therapeutic Benefit]===
*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.
*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.


===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]===
===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===  
*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to [[Abbreviations|'''ADHD''']].
*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://sci-hub.st/https://doi.org/10.1016/j.pbb.2007.09.014 PDF Version]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf 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.
*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.
*Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.
*Keywords: Nicotine, Cholinergic, ADHD, Cognition, Behavioral inhibition, Delay aversion, Methylphenidate, Stop Signal Task, Impulsivity


===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.
*Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
*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


===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]===
===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]===
*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.
*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://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]
*[https://www.karger.com/Article/Pdf/329982 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.
*Funding: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).
*Keywords: ADHD, Transdermal nicotine, CPT, WCST, Stroop, Attention, Memory
*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


===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]
*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


===1996 [https://pubmed.ncbi.nlm.nih.gov/8741955/ Nicotine effects on adults with attention-deficit/hyperactivity disorder]===
===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]===
*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.
*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.


===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.
<br>
<br>


==Mental Health - Anxiety==
='''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
<br>


='''Mental Health'''=
*See subcategories below
<br>
=='''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
<br>


==Mental Health - Behavior Issues==
=='''Mental Health - Behavior Issues'''==  
*See Also: Mental Health - ADD/ADHD above
*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]===
===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
*Human and Animal Studies
*Clinical trials and case series report anti-aggressive effects of nicotine. Here we argue that the [[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.
*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]
*[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.
*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.
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*Keywords: Nicotine, Nicotinic receptor, Aggression, Aggressive behavior, Impulsivity, Acetylcholine
*Keywords: Nicotine, Nicotinic receptor, Aggression, Aggressive behavior, Impulsivity, Acetylcholine


 
===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]===  
===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.  
*Taken together, our study provides evidence for the feasibility and tolerability of [[Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[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.  
*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]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]
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*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).
*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).
*Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep
*Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep
<br>
=='''Mental Health - Depression'''==
===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


==Mental Health - Depression==
===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]===
===2018 [https://pubmed.ncbi.nlm.nih.gov/29795403/ Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder]===  
*In [[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.
*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]
*[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.
*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.
*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]===  
===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.
*[[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.
*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]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129985/pdf/nihms965043.pdf PDF Version]
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*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.
*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]===
===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.
*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.
*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]===  
===1999 [https://link.springer.com/article/10.1007/s002130050879 Antidepressant effects of nicotine in an animal model of depression]===
*Animal Study
*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.
*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 [[Abbreviations|'''FSL''']] rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
*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]
*[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
*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
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*Keywords: Key words Nicotine · Nicotinic receptor · FSL and FRL rats · Animal model of depression  
*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]===  
===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.
*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]
*[https://sci-hub.st/10.1097/00001756-199801050-00012 PDF Version]
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*ACKNOWLEDGEMENT: This work has been supported by the following grants: DGAPA-UNAM IN -200895 to R.J.S-P.
*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]===  
===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.
*A high frequency of cigarette smoking has been reported among individuals with major depression.
*Results of the visual analog scale and [[Abbreviations|'''HAM-D''']] showed a significant improvement in depression after the second day of nicotine patches.
*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.
*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.]===
*
*[https://sci-hub.st/10.1037/0022-006X.64.4.791 PDF Version]
*Citation:


===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
===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)
* 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]
*[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.
*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.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
<br>


=='''Mental Health - Mental Illness'''==


==Mental Health - PTSD (Post Traumatic Stress Disorder==
===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.
<br>


=='''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.
<br>


===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]===
=='''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.
*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]
*[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  
*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.
*Acknowledgement: Department of Veterans Affairs or the National Institutes of Health.
<br>


=='''Mental Health - Schizophrenia'''==
===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]
*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).
*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


===2021 [https://academic.oup.com/ntr/article/23/7/1113/6168972 A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes]===
*A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking. Further research with a larger sample and a comparator group is needed.
*[https://academic.oup.com/ntr/article-pdf/23/7/1113/38521536/ntab005.pdf PDF Version]
*Citation: Pasquale Caponnetto, PhD, Jennifer DiPiazza, PhD, Jason Kim, MD, Marilena Maglia, Lyc Psych, Riccardo Polosa, MD, PhD, A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes, Nicotine & Tobacco Research, Volume 23, Issue 7, July 2021, Pages 1113–1122, 10.1093/ntr/ntab005
*Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.


==Mental Health - Schizophrenia==
===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]===  
 
 
===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.
*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]
*[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 PDF Version]
Line 454: Line 884:
*Keywords: Schizophrenia, Nicotine, Cognition, Early sensory
*Keywords: Schizophrenia, Nicotine, Cognition, Early sensory


=== 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===


===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===
* Ultimately the authors of the study, published in the journal ''Nature Medicine'', envision their work could lead to new non-addictive, nicotine-based treatments for some of the 51 million people worldwide who suffer from the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.
* “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.
* Note: Mouse study; using a model known to mimic human disease.
* 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.
* 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)
 
===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
 
===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.
*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]
*[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.
*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.


===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.
<br>


 
='''Movement Disorders (not diagnosis specific)'''=  
==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]===  
 
 
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149916/ Role for the nicotinic cholinergic system in movement disorders; therapeutic implications]===
*Animal Study
*Animal Study
*Several [[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.
*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]
*[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.
*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.
*Acknowledgements: This work was supported by grants NS59910 and NS 65851 from the National Institutes of Health.
<br>


='''Multiple Sclerosis - Humans / Experimental Autoimmune Encephalomyelitis (EAE) - Animals'''=


=== 2023: [https://www.medscape.com/viewarticle/995075?form=fpf Oral Tobacco Use Linked to Slower MS Progression] ===


==Multiple Sclerosis - Humans / Experimental Autoimmune Encephalomyelitis (EAE) - Animals==
* Jing Wu, Tomas Olsson, Jan Hillert, Lars Alfredsson, Anna Karin Hedström
* Corresponding author Jing Wu, Karolinska Institute, 171 77 Stockholm, Stockholm, Sweden; Email: jing.wu [at] ki.se [Please demangle the email address; spam prevention ed.]
* [https://jnnp.bmj.com/content/94/8/589 Full Text]
* Oral tobacco use, also known as moist snuff, is associated with slower progression of multiple sclerosis (MS), a new study shows.
* Jing Wu, PhD candidate "Our finding that snuff use is not associated with worse disease progression indicates that nicotine replacement therapy could be an attractive way to increase the chance of quitting smoking post diagnosis,"
* To investigate, the researchers analyzed data from 9089 patients with MS who were participants in two case-control studies from the Swedish MS registry, mean age 37.6 years and 72% female. At baseline, current cigarette smokers had significantly higher Expanded Disability Status Scale (EDSS) scores compared with nonsmokers.
* All analyses controlled for age at diagnosis, sex, disease phenotype, disease duration, baseline EDSS, and use of disease-modifying therapy.
* Compared with never smoking, current smoking was associated with an increased risk of clinical disease worsening (CDW) (adjusted hazard ratio [aHR] 1.13; 95% CI 1.06-1.21), of reaching EDSS 3 (aHR 1.21, 95% CI 1.09-1.34), and EDSS 4 (aHR 1.31, 95% CI 1.14-1.51). In addition, compared with never smokers, current smoking was associated with a higher risk of physical and psychological worsening as determined by the MS Impact Scale-29 (MSIS-29), and worsening cognitive performance measured by the Symbol Digit Modalities Test (SDMT).
* The study revealed a dose-dependent relationship between smoking and negative MS-related outcomes.
* Current snuff use was significantly associated with lower risk of reaching EDSS 4 (aHR 0.73, 95% CI 0.58-0.92), but not CDW or EDSS 3. It was not significantly associated with the risk of worsening health-related quality of life or cognition.
* In a perplexing turn of events study co-author Anna Karin Hedström, MD, PhD said "Physicians should not recommend smoking MS patients switch to snuff, as snuff may have other negative health consequences." [Why not? if the alternative is continued smoking? ed.] Particularly considering she also said this "This indicates that nicotine is not the substance that leads to worse prognosis and that nicotine replacement therapy is probably harmless — at least with respect to disease progression."<!--T:186-->


===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]===
===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
*Animal Study
* This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of [[Abbreviations|'''EAE''']] mice via multiple [[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.
* 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]
*[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.
*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.
Line 484: Line 940:
*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]
*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]


===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]===
===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
*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 [[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.
*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]
*[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.
*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.
*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]===
===2013 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659034/ Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis]===  
*Animal Study
*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 [[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 [[Abbreviations|MS]] therapy.
*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]
*[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.
*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.
<br>


='''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]


==OCD (Obsessive Compulsive Disorder)==
===2012: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3311418/ Narcolepsy with Cataplexy Masked by the Use of Nicotine]===


===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528475/ Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review]===
===2010: [https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2823281/ A Novel Approach to Treating Morning Sleep Inertia in Narcolepsy]===
*Nicotine may ameliorate OC symptoms in severe, treatment-refractory [[Abbreviations|'''OCD''']] patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
<br>
*[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.


='''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]===  
==Oral / Jaw==
 
===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.
*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.
*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.
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*Acknowledgements: Funding - CAPES, Ministry of Education, Brazil
*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.
<br>


='''Pain / Analgesic'''=
===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.


==Pain / Analgesic==
===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


===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]===
===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.
*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.
*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.
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*Acknowledgements: Funding - CAPES, Ministry of Education, Brazil
*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]===
===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.  
*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.  
*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 [[Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.  
*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]
*[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.
*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.
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*Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy
*Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy


===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]===
===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.  
*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]
*[https://sci-hub.st/10.1097/EJA.0b013e328344d998 PDF Version]
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*Acknowledgements: The present work was supported solely by the Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
*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]===
===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 [[Abbreviations|'''RRP''']] in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
*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]
*[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
*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


===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
<br>
='''Parkinson Disease'''=
=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38430248/ Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease] ===
* 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.
* Exp Brain Res. 2024 Mar 2. Inam Ullah, Shahab Uddin, Longhe Zhao, Xin Wang, Hongyu Li. PMID: 38430248 DOI: 10.1007/s00221-023-06765-9
* Animal study (worms with humanised neurons)
=== 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.
* Front. Aging Neurosci., 13 September 2023 Sec. Parkinson’s Disease and Aging-related Movement Disorders Volume 15 - 2023 | <nowiki>https://doi.org/10.3389/fnagi.2023.1223310</nowiki>
=== 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.] ===
* 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.
* Mouse study
* Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. eCollection 2023. PMID: 36817162 Free PMC article.
=== 2023: [https://jamanetwork.com/journals/jamaneurology/article-abstract/2805037 Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune] ===
* You have to dig into text and tables to spot “Parkinson disease risk was substantially lower among Black veterans and EVER-SMOKERS (OR 0.49, 95% CI: 0.40-0.61).
* That is a huge benefit that is seemingly not followed up, but probably should be.
* Samuel M. Goldman, MD, MPH; Frances M. Weaver, PhD; Kevin T. Stroupe, PhD; et al JAMA Neurol. Published online May 15, 2023. doi:10.1001/jamaneurol.2023.1168


=== 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] ===


==Parkinson Disease==
* While many reports suggest causality, and often this is a stretch at best, here the authors discuss what is needed to prove a causal relationship and satisfy those requirements.
* It is a rare example of how you should approach causality, reading the text gives a clear account of the criteria the authors consider to prove causality, and how these are met.
* 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.
* Benjamin Mappin-Kasirer, Hongchao Pan, Sarah Lewington, Jennifer Kizza, Richard Gray, Robert Clarke, Richard Peto First published May 5, 2020, DOI: <nowiki>https://doi.org/10.1212/WNL.0000000000009437</nowiki>


===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]===
===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 [[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.  
*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]
*[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
*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
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*Keywords: dietary nicotine, Parkinson disease, neurodegenerative disease
*Keywords: dietary nicotine, Parkinson disease, neurodegenerative disease


===2007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/ Nicotinic receptors as CNS targets for Parkinson’s disease]===
===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
 
===2007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2046219/ Nicotinic receptors as CNS targets for Parkinson’s disease]===  
*Human and animal references
*Human and animal references
*Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
*Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
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*Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.
*Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.


===1996 [https://pubmed.ncbi.nlm.nih.gov/9006184/ Does nicotine have beneficial effects in the treatment of certain diseases?]===
===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 [[Abbreviations|'''Parkinson's Disease''']].
*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.
*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]
*[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.
*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]===
===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)
*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]
*[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.
*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.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
<br>


 
='''Psoriasis'''=  
 
===2012 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/ Can nicotine use alleviate symptoms of psoriasis?]===  
==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.  
*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]
*[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.
*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.
<br>


 
='''Pyoderma Gangrenosum'''=  
 
===2004 [https://pubmed.ncbi.nlm.nih.gov/15204166/ Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream]===  
==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.
*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]
*[https://scihubtw.tw/10.1080/09546630310019364 PDF Version]
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*Keywords: Pyoderma gangrenosum — Topical nicotine cream — Treatment
*Keywords: Pyoderma gangrenosum — Topical nicotine cream — Treatment


===1998 [https://jamanetwork.com/journals/jamadermatology/fullarticle/189304?fbclid=IwAR33gpEktRMf2Q0v5Btl9C5E8gmXw-ZP8_gDFt6sebxUBpXE_WfVt-o-mSw Nicotine for Pyoderma Gangrenosum]===
===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.
*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]
*[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
*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]===
===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.
*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]
*[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.
*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.
<br>


 
='''Sarcoidosis'''=
 
===2021 [https://journal.chestnet.org/article/S0012-3692(21)01282-4/fulltext Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis]===
==Sarcoidosis==
===2021 [https://journal.chestnet.org/article/S0012-3692(21)00962-4/fulltext A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis]===  
 
===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]===  
===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.
*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]
*[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
*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
*Acknowledgements: This work was supported by the American Thoracic Society and the Foundation for Sarcoidosis Research. © 2013 American College of Chest Physicians
<br>


='''Seizures / Epilepsy'''=


===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.


==Seizures / Epilepsy==
===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.


===2012 [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2012.03715.x Resolution of epileptic encephalopathy following treatment with transdermal nicotine]===
===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.
 
===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.
*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]
*[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
*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
*Acknowledgments: We thank Dr. Marcio Sotero De Menezes for suggesting the nicotine patch treatment in our patient following resolution of epilepsy in his patient with a similar presentation.
*Key Words: Autosomal dominant nocturnal frontal lobe epilepsy, Nicotinic acetylcholine receptors, Refractory epilepsy.


===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]===
===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 [[Abbreviations|'''ADNFLE''']], nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
*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]
*[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
*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
*Acknowledgments: The Pharmacy Department undertook randomization and allocation of the trial phase. Nicotine patches and matching placebo patches were provided through SmithKlineBeecham Consumer Healthcare Australia. The patient was cooperatively conscientious in her documentation of seizures. Dr. Stephen Johnson provided helpful comments on nicotinic receptor pharmacology.
<br>
 
 
 
== Sleep Apnea==


===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
='''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)
*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]
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
Line 645: Line 1,178:
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
*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.
<br>


==Smoking Cessation - Nicotine Replacement Therapy (NRT)==
='''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]===  
 
 
==Smoking Cessation / Preventing Relapse (All non-NRT nicotine products)==
 
 
===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
*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]===  
===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub5/full Electronic cigarettes for smoking cessation]===
*This wiki page shows over 70 studies demonstrating these products help people stop smoking.
*Cochrane review of 56 peer-reviewed studies, 12,804 participants (Cochrane is the global gold standard for evidence reviews).  “There is moderate‐certainty evidence that e-cigarettes increase quit rates compared to [nicotine patches & gum].”
*Citation: Hartmann-Boyce  J, McRobbie  H, Butler  AR, Lindson  N, Bullen  C, Begh  R, Theodoulou  A, Notley  C, Rigotti  NA, Turner  T, Fanshawe  TR, Hajek  P. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD010216. DOI:10.1002/14651858.CD010216.pub5. Accessed 28 July 2021.
 
 
===2021: [https://academic.oup.com/ntr/article/23/7/1113/6168972 A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes]===
*A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking.
*[https://scholar.google.com/scholar_url?url=https://academic.oup.com/ntr/article-pdf/23/7/1113/38521536/ntab005.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=yBQBYYa-NZHsyQTPkaSoDg&scisig=AAGBfm3GpEvV3isL4-eiS-xFao9KegDu2Q PDF Version]
*Citation: Pasquale Caponnetto, PhD, Jennifer DiPiazza, PhD, Jason Kim, MD, Marilena Maglia, Lyc Psych, Riccardo Polosa, MD, PhD, A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes, Nicotine & Tobacco Research, Volume 23, Issue 7, July 2021, Pages 1113–1122, doi:10.1093/ntr/ntab005
*Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.
 
 
===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub5/full Electronic cigarettes for smoking cessation]===
*There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT.
*Citation: Hartmann-Boyce J, McRobbie H, Lindson N, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Butler AR, Fanshawe TR, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2021 Apr 29;4(4):CD010216. doi: 10.1002/14651858.CD010216.pub5. PMID: 33913154; PMCID: PMC8092424.
 
 
===2021: [https://onlinelibrary.wiley.com/doi/10.1111/add.15628?fbclid=IwAR1Dliz9fOj83wYQ3muEXwsV_ZdVvi0d-ggBaJStLJqVl0Va3dpHfwt0Twg E-cigarettes versus nicotine replacement treatment as harm reduction interventions for smokers who find quitting difficult: Randomised controlled trial]===
*Participants previously unable to stop smoking with conventional treatments.
*Validated smoking reduction (including cessation) was achieved by 26.5% vs 6.0% of participants in the EC and NRT study arms, respectively. Sustained validated abstinence rates at 6 months were 19.1% vs 3.0%.
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.15628 PDF Version]
*Citation: Myers Smith, K., Phillips-Waller, A., Pesola, F., McRobbie, H., Przulj, D., Orzol, M., and Hajek, P. (2021) E-cigarettes versus nicotine replacement treatment as harm reduction interventions for smokers who find quitting difficult: Randomised controlled trial. Addiction, doi.org/10.1111/add.15628
*Acknowledgements: The study was funded by a Tobacco Advisory Group project grant, Cancer Research UK (C6815/A20503).
 
 
===2021: [https://pubmed.ncbi.nlm.nih.gov/33798919/ A systematic review of randomized controlled trials and network meta-analysis of e-cigarettes for smoking cessation]===
*Smokers assigned to use nicotine e-cigarettes were more likely to remain abstinent from smoking than those assigned to use licensed NRT, and both were more effective than usual care or placebo conditions.
*Citation: Chan GCK, Stjepanović D, Lim C, Sun T, Shanmuga Anandan A, Connor JP, Gartner C, Hall WD, Leung J. A systematic review of randomized controlled trials and network meta-analysis of e-cigarettes for smoking cessation. Addict Behav. 2021 Aug;119:106912. doi: 10.1016/j.addbeh.2021.106912. Epub 2021 Mar 15. PMID: 33798919.
 
 
===2021: [https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-021-00475-7 Electronic cigarettes in standard smoking cessation treatment by tobacco counselors in Flanders: E-cigarette users show similar if not higher quit rates as those using commonly recommended smoking cessation aids]===
*One third of the total sample was biochemically verified smoking abstinent 7 months after quit date, with e-cigarette users (40%) having significantly higher chances to be smoking abstinent than NRT users (23%).
*[https://harmreductionjournal.biomedcentral.com/track/pdf/10.1186/s12954-021-00475-7.pdf PDF Version]
*Citation: Adriaens, K., Belmans, E., Van Gucht, D. et al. Electronic cigarettes in standard smoking cessation treatment by tobacco counselors in Flanders: E-cigarette users show similar if not higher quit rates as those using commonly recommended smoking cessation aids. Harm Reduct J 18, 28 (2021). https://doi.org/10.1186/s12954-021-00475-7
*Acknowledgement: This research received no external funding. EB is supported by a PhD-fellowship of the Research Foundation – Flanders (FWO-Vlaanderen; 1177820N).
 
 
===2021: [https://ash.org.uk/wp-content/uploads/2021/06/Use-of-e-cigarettes-vapes-among-adults-in-Great-Britain-2021.pdf Use of e-cigarettes (vapes) among adults in  Great Britain]===
*Nearly two thirds of current vapers are ex-smokers (64.6%), and the proportion continues to grow, while the proportion who also smoke (known as dual users) has fallen to 30.5% in 2021.
*Fewer than 1% of never smokers are current vapers (amounting to 4.9% of vapers).
*As in previous years the main reason given by ex-smokers for vaping is to help them quit (36%) then to prevent relapse (20%).
*The main reason given by current smokers for vaping is to cut down (26%) then to help them quit (17%) and to prevent relapse (14%).
*Nearly a third of smokers incorrectly believe vaping is more or equally as harmful as smoking (32% compared to 34% in 2020).
*Citation: Action on Smoking and Health (ASH). Use of e-cigarettes (vapes) among adults in Great Britain. 2021
 
 
===2021: [https://www.sciencedirect.com/science/article/abs/pii/S0306460321002227 Predictors of smoking reduction among african american and latinx smokers in a randomized controlled trial of JUUL e-cigarettes]===
*Minority smokers decreased cigarette consumption in a trial of e-cigarettes.
*Smoking reduction was associated with a higher number of JUUL pods used.
*Lower baseline cigarette dependence predicted greater smoking reduction.
*Lower baseline cotinine predicted greater smoking reduction.
*Citation: Dana Rubenstein, Alexander W. Sokolovsky, Elizabeth R. Aston, Nicole L. Nollen, Christopher H. Schmid, Myra Rice, Kim Pulvers, Jasjit S. Ahluwalia, Predictors of smoking reduction among african american and latinx smokers in a randomized controlled trial of JUUL e-cigarettes, Addictive Behaviors, 2021, 107037, ISSN 0306-4603, doi: 10.1016/j.addbeh.2021.107037
 
 
===2021: [https://pubmed.ncbi.nlm.nih.gov/34215994/ Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center]===
*Among primary care patients at a community health center, e-cigarette use was reported by a sizeable portion of the sample. Overall, odds of use were higher in certain patient populations, and individuals who formally used cigarettes were more likely to report e-cigarette use than individuals who currently smoke, suggesting that e-cigarettes may be functioning as a cessation aid or a strategy to reduce conventional cigarette use.
*Citation: O'Cleirigh C, King D, Stanton AM, Goldin A, Kirakosian N, Crane HM, Grasso C. Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center. J Community Health. 2021 Jul 2. doi: 10.1007/s10900-021-01015-x. Epub ahead of print. PMID: 34215994.
*Acknowledgement: The data is owned by a third-party organization (Fenway Health), and the organization’s IRB restricts access to patient data, due to concerns over a risk of inadvertent disclosure of personal health information. Given that the data are abstracted from patients’ primary care medical visits, the preparation of deidentified data is not permitted. Researchers with a reasonable request for a deidentified data set can contact the Fenway Health IRB
 
 
===2021: [https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(20)30307-8/fulltext Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial]===
*A targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes.
*[https://www.thelancet.com/action/showPdf?pii=S2468-2667%2820%2930307-8 PDF Version]
*Citation: doi: 10.1016/S2468-2667(20)30307-8
*Acknowledgement: This work was supported by the National Institute on Drug Abuse of the NIH (R01DA037961). his work has also been supported in part by the Biostatistics and Bioinformatics Shared Resource and the Participant Research, Interventions, and Measures Resource at the H Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute designated Comprehensive Cancer Center (P30CA76292).
 
 
===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186418/ A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes]===
*An estimated 60%–90% of people with schizophrenia smoke, compared with 15%–24% of the general population, exacerbating the already high morbidity and mortality rates observed in this population.
*Pilot Study - only 40 participants
*Sixteen (40%) participants quit by the end of 12 weeks. For the whole sample, we observed an overall, sustained 50% reduction in smoking or smoking abstinence in 37/40 (92.5%) of participants and an overall 75% reduction in median cigarettes per day from 25 to six was observed by the end of the 12 weeks.
*A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking. Considering that most people with schizophrenia spectrum disorders continue smoking, alternative and efficient interventions to reduce or prevent morbidity and mortality are urgently needed.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186418/pdf/ntab005.pdf PDF Version]
*Citation: Caponnetto P, DiPiazza J, Kim J, Maglia M, Polosa R. A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes. Nicotine Tob Res. 2021;23(7):1113-1122. doi:10.1093/ntr/ntab005
*Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.
 
 
===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981929/ Reducing the smoking-related health burden in the USA through diversion to electronic cigarettes: a system dynamics simulation study]===
*The simulation suggests that the promotion of e-cigarettes as a harm-reduction policy is a viable strategy, given current evidence that e-cigarettes offset or divert from smoking. Given the strong effects of implementation challenges on policy effectiveness in the short term, accurately modeling such obstacles can usefully inform policy design.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981929/pdf/12954_2021_Article_484.pdf PDF Version]
*Citation: Selya AS. Reducing the smoking-related health burden in the USA through diversion to electronic cigarettes: a system dynamics simulation study. Harm Reduct J. 2021;18(1):36. Published 2021 Mar 20. doi:10.1186/s12954-021-00484-6
*Acknowledgement: This work was supported by the National Institute for General Medical Sciences (NIGMS) within the National Institutes of Health (NIH), grant number P20GM121341; by the Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education (DIKU), grant number NNA-2016/10023. After the initial submission of this manuscript, AS became employed by Pinney Associates, Inc. which provides consulting services on tobacco harm minimization to JUUL Labs, Inc. The content presented here precedes this competing interest, and JUUL Labs, Inc. and PinneyAssociates, Inc. had any role in the conceptualization, design, analysis, interpretation, or presentation of data, nor in the decision to publish.
 
 
===2021: [https://onlinelibrary.wiley.com/doi/abs/10.1111/add.15597 Changes in dependence, withdrawal, and craving among adult smokers who switch to nicotine salt pod-based e-cigarettes]===
*Smokers who switch to nicotine salt pod system e-cigarettes maintain their nicotine levels and transfer their dependence, suggesting that nicotine salt pod system e-cigarettes have a similar reinforcement potential to cigarettes and facilitate switching.
*Must pay to view whole study / PDF
*Citation: Leavens, E. L. S., Nollen, N. L., Ahluwalia, J. S., Mayo, M. S., Rice, M., Brett, E. I., and Pulvers, K. (2021) Changes in dependence, withdrawal, and craving among adult smokers who switch to nicotine salt pod-based e-cigarettes. Addiction, doi: 10.1111/add.15597.
 
 
===2021: [https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab148/6322566 Reappraising Choice in Addiction: Novel Conceptualizations and Treatments for Tobacco Use Disorder]===
*Given the advent of novel, alternative tobacco products, Tobacco Use Disorder must be conceptualized within a contemporary framework that includes harm reduction and alternative outcomes.
*[https://academic.oup.com/ntr/advance-article-pdf/doi/10.1093/ntr/ntab148/39068104/ntab148.pdf PDF Version]
*Citation: Amanda M Palmer, PhD, Benjamin A Toll, PhD, Matthew J Carpenter, PhD, Eric C Donny, PhD, Dorothy K Hatsukami, PhD, Alana M Rojewski, PhD, Tracy T Smith, PhD, Mehmet Sofuoglu, MD, PhD, Johannes Thrul, PhD, Neal L Benowitz, MD, On Behalf of the Society for Research on Nicotine & Tobacco Treatment Network, Reappraising Choice in Addiction: Novel Conceptualizations and Treatments for Tobacco Use Disorder, Nicotine & Tobacco Research, 2021;, ntab148, doi: 10.1093/ntr/ntab148
*Acknowledgement: This research was supported by by NIH Institutional Postdoctoral Training Grant NIHT32-HL144470, NIDA grant K01DA047433 (Smith), and NCI grant K07CA214839 (Rojewski), and the Hollings Cancer Center (P30 CA138313).
 
 
===2020: [https://pubmed.ncbi.nlm.nih.gov/32770246/ QuitNic: A pilot randomised controlled trial comparing nicotine vaping products with nicotine replacement therapy for smoking cessation following residential detoxification]===
*This pilot study showed that smoking cessation support involving options for nicotine replacement and Quitline-delivered cognitive behavioural counselling is attractive to people after they have been discharged from SUD (Substance Use Disorder) treatment.
*Retention was 63% at 6-weeks and 50% at 12-weeks. At 12-weeks, 68% of the NRT group reported using combination NRT while 96% of the NVP group used the device. Acceptability ratings for the products were high in both groups. At 12-weeks, 14% of the NVP group and 18% of the NRT group reported not smoking at all in the last 7 days. Mean CPD (Cigarettes Per Day) among continued smokers decreased significantly between baseline to 12-weeks in both groups; from 19.91 to 4.72 for the NVP group (p<0.001) and from 20.88 to 5.52 in the NRT group (p<0.001). Cravings and withdrawal symptoms significantly decreased for both groups.
*[https://sci-hub.se/10.1093/ntr/ntaa143 PDF Version]
*Citation: Bonevski, B., Manning, V., Wynne, O., Gartner, C., Borland, R., Baker, A. L., … Lubman, D. I. (2020). QuitNic: A pilot randomised controlled trial comparing nicotine vaping products with nicotine replacement therapy for smoking cessation following residential detoxification. Nicotine & Tobacco Research. doi:10.1093/ntr/ntaa143
*Acknowledgement: This study was supported by a VicHealth Innovation Research Grant (2016-0096).
 
 
===2020: [https://academic.oup.com/ntr/article/23/4/625/5906696?login=true Effectiveness of Electronic Cigarettes in Smoking Cessation: a Systematic Review and Meta-Analysis]===
*Our results suggest that nicotine-ECs may be more effective in smoking cessation when compared to placebo ECs or NRT.
*[https://sci-hub.st/10.1093/ntr/ntaa181 PDF Version]
*Citation: Igor Grabovac, MD, DSc, Moritz Oberndorfer, MSc, Jismy Fischer, Winfried Wiesinger, Sandra Haider, PhD, Thomas Ernst Dorner, MD, MPH, Effectiveness of Electronic Cigarettes in Smoking Cessation: A Systematic Review and Meta-analysis, Nicotine & Tobacco Research, Volume 23, Issue 4, April 2021, Pages 625–634, doi: 10.1093/ntr/ntaa181
*Acknowledgement: This study was funded by the Health Insurance Group of Styria (Steiermärkische Gebietskrankenkasse).
 
 
===2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301047/ Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session]===
*In E3, nicotine e-cigarettes plus counseling was superior to counseling alone for smoking cessation. Non-nicotine e-cigarettes plus counseling was also more effective compared with counseling alone though its effects on cessation were modest. This trial demonstrates the efficacy of e-cigarettes as a tool for smoking cessation compared with counseling alone.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301047/pdf/11883_2020_Article_856.pdf PDF Version]
*Citation: Jia X, Al Rifai M, Liu J, Agarwala A, Gulati M, Virani SS. Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session. Curr Atheroscler Rep. 2020;22(8):32. Published 2020 Jun 18. doi:10.1007/s11883-020-00856-6
 
 
===2020: [https://academic.oup.com/ntr/article-abstract/23/4/654/5895499 A magic bullet? The potential impact of e-cigarettes on the toll of cigarette smoking]===
*The combination of assumptions produces 360 possible scenarios. 357 (99%) yield positive estimates of life-years saved (LYS) due to vaping by 2100, from 143,000 to 65 million.
*The impact of vaping is greatest when it most helps smokers who otherwise have the greatest difficulty quitting smoking.
*Vaping is highly likely to reduce smoking-produced mortality. Still, vaping is not “the” answer to the public health crisis created by smoking. Rather, it may well be a tool to add to the armamentarium of effective tobacco control measures.
*Harm reduction can, and many would say should, be a part of the complex formula that will eventually bring about the demise of smoking.
*[https://sci-hub.se/10.1093/ntr/ntaa160 PDF Version]
*Citation: Mendez, D., & Warner, K. E. (2020). A magic bullet? The potential impact of e-cigarettes on the toll of cigarette smoking. Nicotine & Tobacco Research. doi:10.1093/ntr/ntaa160
*Acknowledgement: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (NIH) and FDA Center for Tobacco Products (CTP) (Award Number U54CA229974).
 
 
===2020: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaa182/5906689?redirectedFrom=fulltext Patterns of e-cigarette use and subsequent cigarette smoking cessation over two years (2013/2014 to 2015/2016) in the Population Assessment of Tobacco and Health (PATH) Study]===
*Smoking cessation was more likely among frequent e-cigarette users, users of e-cigarettes in last quit attempt, and users of flavored and rechargeable devices.
*In this study, the proportion of US adults who incorrectly perceived e-cigarettes as equal to, or more, harmful than cigarettes increased steadily regardless of smoking or vaping status. Current adult smokers appear to be poorly informed about the relative risks of e-cigarettes yet have potentially the most to gain from transitioning to these products. The findings of this study emphasise the urgent need to accurately communicate the reduced relative risk of e-cigarettes compared to continued cigarette smoking and clearly differentiate absolute and relative harms.
*The lack of accurate and consistent messaging from both public health agencies and the media may be contributing to public, and more specifically adult smokers’, perceptions about the relative risk of nicotine when decoupled from combustion and tobacco smoke.
*Confusion may potentially be discouraging adult smokers from using alternative, less hazardous products which may ultimately result in a missed opportunity to positively impact health at both an individual and population level.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501702/pdf/12954_2020_Article_410.pdf PDF Version]
*Citation: Allison M Glasser, MPH, Mahathi Vojjala, MPH, Jennifer Cantrell, DrPH, MPA, David T Levy, PhD, Daniel P Giovenco, PhD, MPH, David Abrams, PhD, Raymond Niaura, PhD, Patterns of E-cigarette Use and Subsequent Cigarette Smoking Cessation Over 2 Years (2013/2014–2015/2016) in the Population Assessment of Tobacco and Health Study, Nicotine & Tobacco Research, , ntaa182, doi: 10.1093/ntr/ntaa182
*Acknowledgement: The paper was funded by Imperial Brands Plc.
 
 
===2020: [https://journals.sagepub.com/doi/full/10.1177/1757913920912436 Using e-cigarettes for smoking cessation: evaluation of a pilot project in the North West of England]===
*Of the 1022 participants who engaged with the pilot 614 were still engaged at 4 weeks, of whom 62% had quit smoking. Of those who still smoked tobacco at week 4, smoking had reduced from a baseline of 19.1 cigarettes/day to 8.7. Overall, 37% of those initially enrolled were confirmed to be using an e-cigarette on its own at follow-up. Successful quit was associated with occupation (unemployed, 33% vs intermediate, 47%) and residing in the less deprived quintiles of deprivation (50% vs 34% in the most deprived quintile.
*E-cigarettes appear to be an effective nicotine replacement therapy
*[https://sci-hub.st/10.1093/ntr/ntaa182 PDF Version]
*Citation: OUP accepted manuscript. (2020). Nicotine & Tobacco Research. doi:10.1093/ntr/ntaa182
*Acknowledgement: This work was funded internally by NYU School of Global Public Health. DTL was also funded in part by the National Cancer Institute (P01CA200512).
 
 
===2020: [https://www.emerald.com/insight/content/doi/10.1108/DAT-02-2020-0007/full/html Tobacco harm reduction in the 21st century]===
*Covers Snus and smokeless tobacco, Heat not burn, and  e-cigarettes
*In conclusion, to reduce smoking and to save millions of lives, tobacco harm reduction in the form of cigarette substitution with low-risk products appears to be a promising path. These products, although not completely risk-free, offer an alternative to quit or die. In consideration of the available evidence, advice to tobacco smokers should include trying substitute products. The obvious fact so often overlooked is that smoking is rewarding and people like to do it. Giving smokers an alternative with efficient nicotine delivery means that they might prefer one of these products over cigarettes.
*[https://www.emerald.com/insight/content/doi/10.1108/DAT-02-2020-0007/full/pdf?title=tobacco-harm-reduction-in-the-21st-century PDF Version] and [https://safernicotine.wiki/mediawiki/index.php/File:Ren%C3%A9e_O%E2%80%99Leary_and_Riccardo_Polosa.pdf PDF2]
*Citation: O'Leary, R. and Polosa, R. (2020), "Tobacco harm reduction in the 21st century", Drugs and Alcohol Today, Vol. 20 No. 3, pp. 219-234. doi: 10.1108/DAT-02-2020-0007
 
 
===2019: [https://www.journalslibrary.nihr.ac.uk/hta/hta23430#/abstract E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT]===
*The primary outcome was CO-validated sustained abstinence rates at 52 weeks. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers.
*The 1-year quit rate was 9.9% in the NRT arm and 18.0% in the e-cigarette arm.
*The e-cigarette arm had significantly higher validated quit rates at all time points. Participants in the e-cigarette arm showed significantly better adherence and experienced fewer urges to smoke throughout the initial 4 weeks of their quit attempt than those in the NRT arm, and gave their allocated product more favourable ratings. They were also more likely to be still using their allocated product at 1 year
*Participants assigned to e-cigarettes reported significantly less coughing and phlegm at 1 year than those assigned to NRT
*A detailed economic analysis confirmed that, because e-cigarettes incur lower NHS costs than NRT and generate a higher quit rate, e-cigarette use is more cost-effective.
*[https://njl-admin.nihr.ac.uk/document/download/2030301 PDF Version]
*Citation: Hajek P, Phillips-Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, et al. E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT. Health Technol Assess 2019;23(43)
*Acknowledgement: This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care.
 
 
===2019: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.14829 Cost‐effectiveness of e‐cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial]===
*Using e‐cigarettes as a smoking cessation aid with standard behavioural support in stop‐smoking services in England is likely to be more cost‐effective than using nicotine replacement therapy in the same setting.
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.14829 PDF Version]
*Citation: Li, J., Hajek, P., Pesola, F., Wu, Q., Phillips-Waller, A., Przulj, D., Myers Smith, K., Bisal, N., Sasieni, P., Dawkins, L., Ross, L., Goniewicz, M. L., McRobbie, H., and Parrott, S. (2020) Cost-effectiveness of e-cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial. Addiction, 115: 507– 517. https://doi.org/10.1111/add.14829.
*Acknowledgement: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (12/167/135) and by a grant (A16893) from the Cancer Research UK Prevention Trials Unit.
 
 
===2019: [https://pubmed.ncbi.nlm.nih.gov/31300577/ Effect of Electronic Cigarettes on Smoking Reduction and Cessation in Korean Male Smokers: A Randomized Controlled Study]===
* In our study, the effect of e-cigarettes on smoking cessation was similar compared with that of nicotine gum, a well-documented NRT. In addition, e-cigarettes were well tolerated by the study population. Therefore, the use of e-cigarettes as an NRT may be considered for smoking-cessation purposes.
*[https://sci-hub.se/10.3122/jabfm.2019.04.180384 PDF Version]
*Citation: Effect of Electronic Cigarettes on Smoking Reduction and Cessation in Korean Male Smokers: A Randomized Controlled Study; Seung-Hwa Lee, Sang-Hyun Ahn, Yoo-Seock Cheong; The Journal of the American Board of Family Medicine Jul 2019, 32 (4) 567-574; DOI: 10.3122/jabfm.2019.04.180384
*Acknowledgement: No outside funding
 
 
===2019: [https://www.nejm.org/doi/10.1056/NEJMoa1808779 A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy]===
*A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.
*Conclusion: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support.
*[https://www.nejm.org/doi/pdf/10.1056/NEJMoa1808779 PDF Version]
*Citation: Hajek P, Phillips-Walker A, Przulj D, et al. (2019). A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629–37; doi: 10.1056/NEJMoa1808779.
*Acknowledgement: Supported by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number, 12/167/135) and by a grant (A16893) from the Cancer Research UK Prevention Trials Unit.
 
 
===2019: [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30269-3/fulltext Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial]===
*In summary, when looking at continuous abstinence from smoking, provision of patches plus a nicotine e-cigarette resulted in three to seven more smokers per 100 quitting long-term (depending on the analyses done) than with patches plus a nicotine-free e-cigarette. The smaller than anticipated sample size meant the study was not sensitive enough to pick up a definitive finding for the second comparison, although analyses suggest combination nicotine therapy—ie, use of a slow release nicotine patch, together with a faster-acting oral nicotine product (in this case a nicotine e-cigarette)—could result in five to ten more smokers per 100 quitting long-term than with monotherapy (ie, nicotine patches alone). Our findings are consistent with the current findings of the Cochrane review of e-cigarettes for smoking cessation and contribute to the growing body of evidence from randomised trials on the efficacy, effectiveness and safety of e-cigarettes for smoking cessation.
*[https://www.nejm.org/doi/pdf/10.1056/NEJMoa1808779 PDF Version]
*Citation: Walker, N., Parag, V., Verbiest, M., Laking, G., Laugesen, M., & Bullen, C. (2019). Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. The Lancet Respiratory Medicine. doi:10.1016/s2213-2600(19)30269-3
*Acknowledgement: Funded by Health Research Council of New Zealand.
 
 
===2019: [https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2737916 Association Between Electronic Cigarette Use and Smoking Reduction in France]===
*This cohort study found that, among daily smokers in France, regular (daily) electronic cigarette use is associated with a significantly higher decrease in the number of cigarettes smoked per day as well as an increase in smoking cessation attempts. However, among former smokers, electronic cigarette use is associated with an increase in the rate of smoking relapse.
*[https://sci-hub.se/10.1001/jamainternmed.2019.1483 PDF Version]
*Citation: Gomajee, R., El-Khoury, F., Goldberg, M., Zins, M., Lemogne, C., Wiernik, E., … Melchior, M. (2019). Association Between Electronic Cigarette Use and Smoking Reduction in France. JAMA Internal Medicine. doi:10.1001/jamainternmed.2019.1483
*Acknowledgement: The CONSTANCES (Consultants des Centres d’Examens de Santé) Cohort Study was supported and funded by the Caisse nationale d’assurance maladie des travailleurs salariés. The CONSTANCES Cohort Study is an “Infrastructure nationale en Biologie et Santé” is funded by grant ANR-11-INBS-0002 from Agence Nationale de la Recherche. CONSTANCES is also partly funded by MSD, AstraZeneca, and Lundbeck. The present analyses were supported by grant 2016-082 from Institut National du Cancer.
*'''NOTE''': Article that covers above study - [https://www.cnn.com/2019/07/15/health/e-cigarettes-quit-smoking-study/index.html?no-st=1565360238 Adults who vape are more likely to quit cigarettes, study finds]
**“The study did find that the heightened risk of relapse disappeared in those who quit smoking more recently, which the researchers said may be due to improved e-cigarette technology.”
**“For example, the study as a whole considered anybody who quit smoking from 2010 onward and found that, in that sample, vaping increased the risk of relapse. But when researchers only considered people who quit cigarettes as of 2013, former smokers were not more likely to relapse if they vaped.”
**“The researchers noted in their study that "measures of plasma nicotine levels have shown that, compared with older models of [e-cigarettes], the new generation delivers higher levels of nicotine to the bloodstream," which may make them more satisfying.”
**“Other "technical improvements in [e-cigarettes] over time," they said, may also explain why people who recently quit smoking and switched to e-cigarettes were less likely to relapse than those who quit earlier.”
 
 
===2019: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.14851 Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time–series analysis between 2007 and 2017]===
*The increase in prevalence of e‐cigarette use by smokers in England has been positively associated with an increase in success rates of quit attempts and overall quit rates
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.14851 PDF Version]
*Citation: Beard, E., West, R., Michie, S., and Brown, J. (2020) Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time–series analysis between 2006 and 2017. Addiction, 115: 961– 974. doi: 10.1111/add.14851.
*Acknowledgement: The STS is currently primarily funded by Cancer Research UK (C1417/A14135; C36048/A11654; C44576/A19501), and has previously also been funded by Pfizer, GlaxoSmithKline and the Department of Health.
 
 
===2019: [https://academic.oup.com/ntr/article-abstract/22/5/728/5531618 Electronic Cigarette Use and Cigarette Abstinence Over 2 Years Among U.S. Smokers in the Population Assessment of Tobacco and Health Study]===
*In this nationally representative longitudinal cohort study of US adult cigarette smokers, daily e-cigarette use, compared to no e-cigarette use, was associated with a 77% increased odds of prolonged cigarette smoking abstinence over the subsequent 2 years. Regular use of e-cigarettes may help some smokers to stop smoking combustible cigarettes.
*[https://sci-hub.se/10.1093/ntr/ntz114 PDF Version]
*Citation: Kalkhoran, S., Chang, Y., & Rigotti, N. A. (2019). Electronic Cigarette Use and Cigarette Abstinence Over Two Years among U.S. Smokers in the Population Assessment of Tobacco and Health Study. Nicotine & Tobacco Research. doi:10.1093/ntr/ntz114
*Acknowledgement: This study was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (K23HL136854 to Dr. Kalkhoran).
*Article: [https://medicalxpress.com/news/2019-07-daily-e-cigarette-smokers-regular-cigarettes.amp?__twitter_impression=true&fbclid=IwAR31bxC-WqHdBdIjXClI6fA9qOVsnPAP90sUGDAHHHJuW0xw-VANcuFsT1A Daily e-cigarette use may help smokers quit regular cigarettes]
 
 
===2019: [https://onlinelibrary.wiley.com/doi/10.1111/add.14722 Indicators of cigarette smoking dependence and relapse in former smokers who vape compared with those who do not: findings from the 2016 International Tobacco Control Four Country Smoking and Vaping Survey]===
*Vapers were more likely than non-vapers to report: (1) having smoked within 5 minutes of waking; having smoked > 10 cigarettes/day; (2) perceiving themselves to be still very addicted to smoking and feeling extremely confident about staying quit.
*In totality, therefore, our findings favour the first explanation, that in our sample the daily vapers had been a more highly dependent group than the non-vapers, which would support the suggestion that vaping might be offering a novel route out of smoking for this group of smokers, albeit maintaining their nicotine addiction.
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.14722 PDF Version]
*Citation: McNeill, A., Driezen, P., Hitchman, S. C., Cummings, K. M., Fong, G. T., and Borland, R. (2019) Indicators of cigarette smoking dependence and relapse in former smokers who vape compared with those who do not: findings from the 2016 International Tobacco Control Four Country Smoking and Vaping Survey. Addiction, 114( S1): 49– 60. doi: 10.1111/add.14722.
*This study was supported by grants from the US National Cancer Institute P01CA200512, the Canadian Institutes of Health Research (FDN - 148477), and by the National Health and Medical Research Council of Australia (APP1106451). G.T.F. was supported in part from a Senior Investigator Award from the Ontario Institute for Cancer Research.
 
 
===2019: [https://www.cdc.gov/mmwr/volumes/69/wr/mm6946a4.htm?s_cid=mm6946a4_w Tobacco Product Use Among Adults — United States, 2019]===
*4.3 million US adult nicotine vapers are ex-smokers.
*[https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6946a4-H.pdf PDF Version]
*Citation: Cornelius ME, Wang TW, Jamal A, Loretan CG, Neff LJ. Tobacco Product Use Among Adults — United States, 2019. MMWR Morb Mortal Wkly Rep 2020;69:1736–1742. DOI:10.15585/mmwr.mm6946a4
 
 
===2018: [https://www.casaa.org/wp-content/uploads/American-Cancer-Society-Position-Statement-on-Electronic-Cigarettes.pdf American Cancer Society Position Statement on Electronic Cigarettes]===
*Based on currently available evidence, using current generation e-cigarettes is less harmful than smoking cigarettes, but the health effects of long-term use are not known.
*The ACS has always supported any smoker who is considering quitting, no matter what approach they use; there is nothing more important that they can do for their health. Some smokers, despite firm clinician advice, will not attempt to quit smoking cigarettes and will not use FDA approved cessation medications.  These individuals should be encouraged to switch to the least harmful form of tobacco product possible; switching to the exclusive use of e- cigarettes is preferable to continuing to smoke combustible products.
 
 
===2018: [https://onlinelibrary.wiley.com/doi/10.1111/add.14527 Discussions between health professionals and smokers about nicotine vaping products: results from the 2016 ITC Four Country Smoking and Vaping Survey]===
*Despite the need for more evidence on their efficacy and long‐term safety, NVPs are now a more popular method for cessation than licensed NRT and prescription stop‐smoking medications in many countries.
*In light of this, HPs should be prepared to provide balanced information about NVPs, particularly to smokers who are unable to stop smoking with approved cessation therapies, and for those who are requesting guidance regarding NVPs as a smoking cessation aid
*Overall, the results from this study have shown that discussions between smokers and HPs about both quitting smoking, and the possible role NVPs could play as a cessation aid, were infrequent in the four countries in 2016. This may represent a lost opportunity for encouraging quitting smoking by providing a potentially attractive option to help smokers to quit.
*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.14527 PDF Version]
*Citation: Gravely, S., Thrasher, J. F., Cummings, K. M., Ouimet, J., McNeill, A., Meng, G., Lindblom, E. N., Loewen, R., O’Connor, R. J., Thompson, M. E., Hitchman, S. C., Hammond, D., Heckman, B. W., Borland, R., Yong, H.-H., Elton-Marshall, T., Bansal-Travers, M., Gartner, C., and Fong, G. T. (2019) Discussions between health professionals and smokers about nicotine vaping products: results from the 2016 ITC Four Country Smoking and Vaping Survey. Addiction, 114( S1): 71– 85. https://doi.org/10.1111/add.14527.
*Acknowledgement: This study was supported by grants from the US National Cancer Institute (P01 CA200512), the Canadian Institutes of Health Research (FDN-148477) and by the National Health and Medical Research Council of Australia (APP 1106451). S.G. was funded by a 3-year Canadian Cancer Society (CCS) Career Development Award in Cancer Prevention (703858). G.T.F. was supported by a Senior Investigator Award from the Ontario Institute for Cancer Research. B.W.H. was supported by NIDA (K23 DA041616).
 
 
===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
*Acknowledgement: Funding for this study was provided by Nicoventures.
 
 
===2018: [https://tobaccocontrol.bmj.com/content/28/1/42 E-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013–2015]===
*Daily e-cigarette initiators were more likely to have quit smoking cigarettes or reduced use compared with non-users. However, less frequent e-cigarette use was not associated with cigarette cessation/reduction. These results suggest incorporating frequency of e-cigarette use is important for developing a more thorough understanding of the association between e-cigarette use and cigarette cessation.
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/early/2018/03/24/tobaccocontrol-2017-054108.full.pdf PDF Version]
*Citation: Berry KM, Reynolds LM, Collins JM, et alE-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013–2015Tobacco Control 2019;28:42-49.
*Acknowledgement: Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and the Center for Tobacco Products under Award Number P50HL120163.
 
 
===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751520/ E-cigarette Usage Is Associated With Increased Past-12-Month Quit Attempts and Successful Smoking Cessation in Two US Population–Based Surveys]===
*Compared with 2006, past-12-month quit attempts and smoking cessation increased among adults aged 25–44 in recent years. Current e-cigarette use was associated with increased past-12-month quit attempts and successful smoking cessation among established smokers. These findings are relevant to future tobacco policy decisions.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751520/pdf/nty211.pdf PDF Version]
*Citation: Johnson L, Ma Y, Fisher SL, et al. E-cigarette Usage Is Associated With Increased Past-12-Month Quit Attempts and Successful Smoking Cessation in Two US Population-Based Surveys. Nicotine Tob Res. 2019;21(10):1331-1338. doi:10.1093/ntr/nty211
*Acknowledgement: Research reported in this paper was supported by National Institute on Drug Abuse (NIDA) grants R01DA036583 (LJB), R01DA042195 (RAG), R01DA038076 (LSC), R21DA033827 (RCC), and K12DA041449 (ATR); National Cancer Institute (NCI) grants U19CA203654 (LJB), P30CA091842 (LJB), and P30CA091842-16S2 (LSC); National Heart, Lung, and Blood Institute (NHLBI) grant R01HL109031 (TBB), National Institute on Alcohol Abuse and Alcoholism grant R21AA024888 (SMH), National Center For Advancing Translational Sciences grant TL1TR002344 (LJ), a grant from the Foundation for Barnes-Jewish Hospital (ATR), and by Grant 2015215 from the Doris Duke Charitable Foundation (SMH).
 
 
===2017: [https://www.bmj.com/content/358/bmj.j3262 E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys]===
*This study, based on the largest representative sample of e-cigarette users to date, provides a strong case that e-cigarette use was associated with an increase in smoking cessation at the population level. We found that e-cigarette use was associated with an increased smoking cessation rate at the level of subgroup analysis and at the overall population level. It is remarkable, considering that this is the kind of data pattern that has been predicted but not observed at the population level for cessation medication, such as nicotine replacement therapy and varenicline. This is the first statistically significant increase observed in population smoking cessation among US adults in nearly a quarter of a century. These findings need to be weighed carefully in regulatory policy making and in the planning of tobacco control interventions.
*[https://www.bmj.com/content/bmj/358/bmj.j3262.full.pdf PDF Version]
*Citation: Zhu S, Zhuang Y, Wong S, Cummins S E, Tedeschi G J. E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys BMJ 2017; 358 :j3262 doi:10.1136/bmj.j3262
*Acknowledgement: This study was supported by the National Cancer Institute of the National Institutes of Health under the State and Community Tobacco Control (SCTC) Initiative (award No U01CA154280).
 
 
===2017: [https://academic.oup.com/ntr/article-abstract/doi/10.1093/ntr/ntx166/4096490/The-Relationship-of-E-Cigarette-Use-to-Cigarette?redirectedFrom=fulltext The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation: Insights From a Large, Nationally Representative U.S. Survey]===
*Consistent with randomized trials and those observational studies that measure frequency of e-cigarette use, both quit attempts and quit success were positively associated with increased frequency of e-cigarette use. Frequency of e-cigarette use was important in gauging the nature of these relationships.
*[https://sci-hub.st/10.1093/ntr/ntx166 PDF Version]
*Citation: Levy, D. T., Yuan, Z., Luo, Y., & Abrams, D. B. (2017). The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation: Insights From a Large, Nationally Representative U.S. Survey. Nicotine & Tobacco Research, 20(8), 931–939. doi:10.1093/ntr/ntx166
*Acknowledgement: Funding was received by Drs. Levy and Abrams from the National Institute on Drug Abuse under grant R01DA036497. Dr. Levy also received funding from the National Cancer Institute under grant P01-CA200512.
 
 
===2017: [https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntx269/4768299?redirectedFrom=fulltext Predicting Short-Term Uptake of Electronic Cigarettes: Effects of Nicotine, Subjective Effects, and Simulated Demand]===
*Mean cigarettes per day decreased by 37% when e-cigarettes were available relative to baseline. Nicotine-containing cartridges were associated with greater use and craving reduction than 0 mg. Alleviation of withdrawal symptoms and taste and enjoyment factors predicted e-cigarette use.
*[https://sci-hub.se/10.1093/ntr/ntx269 PDF Versioin]
*Citation: Tucker, M. R., Laugesen, M., Bullen, C., & Grace, R. C. (2017). Predicting Short-Term Uptake of Electronic Cigarettes: Effects of Nicotine, Subjective Effects, and Simulated Demand. Nicotine & Tobacco Research. doi:10.1093/ntr/ntx269
*Acknowledge: This research was funded by the Tobacco Control Research Tūranga: A programme of innovative research to halve the smoking prevalence in Aotearoa/New Zealand within a decade. The Tūranga is supported through funding from the Reducing Tobacco-related Harm Research Partnership, co-funded by the Health Research Council of New Zealand and the Ministry of Health of New Zealand (HRC grant: 11/818).
 
===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520273/ Cohort study of electronic cigarette use: effectiveness and safety at 24 months]===
*Of the e-cigarette users, 61.1% remained abstinent from tobacco (while 23.1% and 26.0% of tobacco-only smokers and dual users achieved tobacco abstinence).
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520273/pdf/tobaccocontrol-2015-052822.pdf PDF Version]
*Citation: Manzoli L, Flacco ME, Ferrante M, et al. Cohort study of electronic cigarette use: effectiveness and safety at 24 months. Tob Control. 2017;26(3):284-292. doi:10.1136/tobaccocontrol-2015-052822
*Acknowledgement: The first 2 years of the study were unfunded. The next 3 years of follow-up are going to be funded through crowdfunding (Kickstarter project titled ‘E-cigarette long-term efficacy & safety: a study to complete’).
 
 
===2017: [https://link.springer.com/article/10.1007%2Fs11606-017-4123-x Patterns of and reasons for electronic cigarette use in primary care patients]===
*In descriptive analyses, compared to never e-cigarette users, ever e-cigarette users were younger, non-Hispanic white, more educated, more likely to be daily smokers, smoked more cigarettes per day, and smoked their first cigarette within 30 min of waking.
*Among current e-cigarette users, 84% reported using e-cigarettes to quit cigarettes, to cut down on cigarettes, or because they believe they are less harmful than cigarettes. The least common reason for use was cost (48%). Among former e-cigarette users, 78% reported using e-cigarettes to quit cigarettes, to cut down on cigarettes, or because they believe they are less harmful than cigarettes, and the least common reason was also cost (30%).
*[https://link.springer.com/content/pdf/10.1007/s11606-017-4123-x.pdf PDF Version]
*Citation: Kalkhoran, S., Alvarado, N., Vijayaraghavan, M. et al. Patterns of and reasons for electronic cigarette use in primary care patients. J GEN INTERN MED 32, 1122–1129 (2017). doi:10.1007/s11606-017-4123-x
*Acknowledgement: This work was supported by NIH National Institute on Drug Abuse R01DA034253.
 
 
===2017: [https://europa.eu/eurobarometer/surveys/detail/2146 Attitudes of Europeans towards tobacco and electronic cigarettes]===
*7.5 million EU citizens have quit smoking with nicotine vapes (“e-cigarettes”)
 
 
===2016: [https://tobaccocontrol.bmj.com/content/25/Suppl_1/i90 Long-term e-cigarette use and smoking cessation: a longitudinal study with US population ]===
*Long-term use of e-cigarettes was associated with a higher rate of quitting smoking
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/25/Suppl_1/i90.full.pdf PDF Version]
*Citation: Zhuang Y, Cummins SE, Y Sun J, et alLong-term e-cigarette use and smoking cessation: a longitudinal study with US populationTobacco Control 2016;25:i90-i95.
*Acknowledgement: This study was supported by the National Cancer Institute of the National Institutes of Health under the State and Community Tobacco Control Initiative, Award Number U01CA154280.
 
 
===2016: [https://www.bmj.com/content/354/bmj.i4645 Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends]===
*Changes in prevalence of e-cigarette use in England have been positively associated with the success rates of quit attempts. No clear association has been found between e-cigarette use and the rate of quit attempts or the use of other quitting aids, except for NRT obtained on prescription, where the association has been negative.
*[https://www.bmj.com/content/bmj/354/bmj.i4645.full.pdf PDF Version]
*Citation: Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends BMJ 2016; 354 :i4645 doi:10.1136/bmj.i4645
*Acknowledgement:  The Smoking Toolkit Study is currently primarily funded by Cancer Research UK (C1417/A14135; C36048/A11654; C44576/A19501), and has previously also been funded by Pfizer, GlaxoSmithKline, and the Department of Health.
 
 
===2016: [https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/534708/E-cigarettes_joint_consensus_statement_2016.pdf E-cigarettes: a developing public health consensus]===
*From: Public Health England, Action on Smoking and Health, Association of Directors of Public Health, British Lung Foundation, Cancer Research UK, Faculty of Public Health, Fresh North East, Healthier Futures, Public Health Action, Royal College of Physicians, Royal Society for Public Health, UK Centre for Tobacco and Alcohol Studies, UK Health Forum
*We all agree that e-cigarettes are significantly less harmful than smoking. One in two lifelong smokers dies from their addiction. All the evidence suggests that the health risks posed by e-cigarettes are relatively small by comparison but we must continue to study the long-term effects.
*And yet, millions of smokers have the impression that e-cigarettes are at least as harmful as tobacco
*The public health opportunity is in helping smokers to quit, so we may encourage smokers to try vaping but we certainly encourage vapers to stop smoking tobacco completely.
*We know that e-cigarettes are the most popular quitting tool in the country with more than 10 times as many people using them than using local stop smoking services.
*The current national evidence is that in the UK regular e-cigarette among youth use is almost exclusively confined to those young people who have already smoked, and youth smoking prevalence is continuing to fall.
*We should not forget what is important here. We know that smoking is the number one killer in England and we have a public health responsibility to provide smokers with the information and the tools to help them quit smoking completely and forever.
 
 
===2016: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896829/ Patterns of Electronic Cigarette Use Among Adults in the United States]===
*Results: Current e-cigarette use is extremely low among never cigarette smokers (0.4%) and former smokers who quit cigarettes 4 or more years ago (0.8%). Although e-cigarette experimentation is most common among current cigarette smokers and young adults, daily use is highest among former smokers who quit in the past year (13.0%) and older adults. Compared to daily cigarette smokers, recently quit smokers were more than four times as likely to be daily users of e-cigarettes.
*Conclusion: Extremely low e-cigarette use among never-smokers and longer term former smokers suggest that e-cigarettes neither promote widespread initiation nor relapse among adults. Recognition of the heterogeneity of smokers, including the time since quitting, is critical to draw accurate conclusions about patterns of e-cigarette use at the population level and its potential for public health benefit or harm.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896829/pdf/ntv237.pdf PDF Version]
*Citation: Delnevo CD, Giovenco DP, Steinberg MB, et al. Patterns of Electronic Cigarette Use Among Adults in the United States. Nicotine Tob Res. 2016;18(5):715-719. doi:10.1093/ntr/ntv237
*Acknowledgement: This research was supported in part by funding from the National Institutes of Health (R01CA19044 [CDD and MBS] and K01DA037950 [JLP])
 
===2016: [https://onlinelibrary.wiley.com/doi/abs/10.1111/add.13506 Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries]===
*E‐cigarette use in the European Union appears to be largely confined to current or former smokers, while current use and nicotine use by people who have never smoked is rare. More than one‐third of current e‐cigarette users polled reported smoking cessation and reduction.
*[https://sci-hub.st/10.1111/add.13506 PDF Version]
*Citation: Farsalinos, K. E., Poulas, K., Voudris, V., & Le Houezec, J. (2016). Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries. Addiction, 111(11), 2032–2040. doi:10.1111/add.13506
*Acknowledgement: No funding was provided for this study
 
 
===2016: [https://www.mdpi.com/1660-4601/13/11/1110 Patterns of Smoking and Snus Use in Sweden: Implications for Public Health]===
*“Snus has both contributed to decreasing initiation of smoking and ...appears to facilitate smoking cessation. ...Snus has been a major factor behind Sweden’s record-low prevalence of smoking and lowest tobacco-related mortality among men in Europe.”
*[https://www.mdpi.com/1660-4601/13/11/1110/pdf PDF Version]
*Citation: Ramström, L.; Borland, R.; Wikmans, T. Patterns of Smoking and Snus Use in Sweden: Implications for Public Health. Int. J. Environ. Res. Public Health 2016, 13, 1110. https://doi.org/10.3390/ijerph13111110
 
 
===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378973/ E-Cigarettes and Smoking Cessation: Evidence from a Systematic Review and Meta-Analysis]===
*“This systematic review and meta-analyses assessed the findings of six studies which reported smoking cessation after using e-cigarettes. We found an association between nicotine-enriched e-cigarette use and smoking cessation, suggesting that the devices may be an effective alternative smoking cessation method. We also found that use of e-cigarettes was also associated with a reduction in the number of cigarettes used, suggesting they may also have a role in tobacco harm reduction programs. To our knowledge, this is the most comprehensive evidence to date on this issue, and while there are a number of important implications for further research, these findings provide timely information to inform regulatory strategies.”
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378973/pdf/pone.0122544.pdf PDF Version]
*Citation: Rahman MA, Hann N, Wilson A, Mnatzaganian G, Worrall-Carter L. E-cigarettes and smoking cessation: evidence from a systematic review and meta-analysis. PLoS One. 2015;10(3):e0122544. Published 2015 Mar 30. doi:10.1371/journal.pone.0122544
*Acknowledgement: The authors have no support or funding to report.
 
===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375383/ A Longitudinal Study of Electronic Cigarette Use Among a Population-Based Sample of Adult Smokers: Association With Smoking Cessation and Motivation to Quit]===
*Results: At follow-up, 23% were intensive users, 29% intermittent users, 18% had used once or twice, and 30% had not tried e-cigarettes. Logistic regression controlling for demographics and tobacco dependence indicated that intensive users of e-cigarettes were 6 times more likely than non-users/triers to report that they quit smoking. Daily use of electronic cigarettes for at least 1 month is strongly associated with quitting smoking at follow-up. Further investigation of the underlying reasons for intensive versus intermittent use will help shed light on the mechanisms underlying the associations between e-cigarette use, motivation to quit, and smoking cessation.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375383/pdf/ntu200.pdf PDF Version]
*Citation: Biener L, Hargraves JL. A longitudinal study of electronic cigarette use among a population-based sample of adult smokers: association with smoking cessation and motivation to quit. Nicotine Tob Res. 2015;17(2):127-133. doi:10.1093/ntr/ntu200
*Acknowledgement: This work was supported by a grant from the US National Cancer Institute, grant #R01CA151384-03.
 
 
===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580313/ Associations Between E-Cigarette Type, Frequency of Use, and Quitting Smoking: Findings From a Longitudinal Online Panel Survey in Great Britain]===
*Whether e-cigarette use is associated with quitting depends on type and frequency of use. Compared with respondents not using e-cigarettes, daily tank users were more likely, and non-daily cigalike users were less likely, to have quit. Tanks were more likely to be used by older respondents and respondents with lower education.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580313/pdf/ntv078.pdf PDF Version]
*Citation: Hitchman SC, Brose LS, Brown J, Robson D, McNeill A. Associations Between E-Cigarette Type, Frequency of Use, and Quitting Smoking: Findings From a Longitudinal Online Panel Survey in Great Britain. Nicotine Tob Res. 2015;17(10):1187-1194. doi:10.1093/ntr/ntv078
*Acknowledgement: All authors are members of the UK Centre for Tobacco & Alcohol Studies, a UK Clinical Research Collaboration Public Health Research: Centre of Excellence whose work is supported by funding from the Medical Research Council, British Heart Foundation, Cancer Research UK, Economic and Social Research Council, and the National Institute for Health Research under the auspices of the UK Clinical Research Collaboration is gratefully acknowledged (MR/K023195/1). JB’s post is funded by a fellowship from the UK Society for the Study of Addiction.
 
===2015: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464650/ Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study]===
*Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers...
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464650/pdf/pone.0129443.pdf PDF Version]
*Citation: Manzoli L, Flacco ME, Fiore M, et al. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study. PLoS One. 2015;10(6):e0129443. Published 2015 Jun 10. doi:10.1371/journal.pone.0129443
*Acknowledgement: The authors have no support or funding to report.
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171752/ Real-world effectiveness of e-cigarettes when used to aid smoking cessation: a cross-sectional population study]===
*Conclusion: “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 product bought over-the-counter or no aid to cessation. This difference persists after adjusting for a range of smoker characteristics such as nicotine dependence.”
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171752/pdf/add0109-1531.pdf PDF Version]
*Citation: Brown J, Beard E, Kotz D, Michie S, West R. Real-world effectiveness of e-cigarettes when used to aid smoking cessation: a cross-sectional population study. Addiction. 2014;109(9):1531-1540. doi:10.1111/add.12623
*Acknowledgement: The research team is part of the UK Centre for Tobacco and Alcohol Studies. JB's post is funded by a fellowship from the UK Society for the Study of Addiction; R.W. is funded by Cancer Research UK; Cancer Research UK, the Department of Health and Pfizer funded data collection for this study (including a Pfizer investigator initiated award), and that at the outset data collection for the Smoking Toolkit Study was also supported by GlaxoSmithKline and Johnson and Johnson.
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238186/ E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices]=== 
*Related Article: [https://www.cinj.org/patient-care/e-cigarettes-vs-nicotine-inhalers E-Cigarettes vs. Nicotine Inhalers]
*“In conclusion, during this brief trial, the e-cigarette was found to be more acceptable, provided more satisfaction and rewards, and had higher perceived benefit than the nicotine inhaler. These findings may explain why the e-cigarette has become popular among smokers while the inhaler has not achieved the same favorability. Based on this difference, e-cigarettes could have the potential to become “tobacco cigarette substitutes,” owing to their high acceptance and perceived effectiveness. While toxicants have been identified in e-cigarettes, they are present at orders of magnitude lower than tobacco cigarettes. As such, e-cigarettes may hold value as a harm reduction strategy among those unwilling or unable to quit. However, given the large variation in the market with respect to brands, more data are needed to demonstrate their efficacy and safety, and to allow physicians to more appropriately inform their patients about these products.”
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238186/pdf/11606_2014_Article_2889.pdf PDF Version]
*Citation: Steinberg MB, Zimmermann MH, Delnevo CD, et al. E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices. J Gen Intern Med. 2014;29(11):1444-1450. doi:10.1007/s11606-014-2889-7
*Acknowledgement: This study was funded through a pilot grant from the Rutgers–Cancer Institute of New Jersey (P30CA072720).
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245610/ Effectiveness of the Electronic Cigarette: An Eight-Week Flemish Study with Six-Month Follow-up on Smoking Reduction, Craving and Experienced Benefits and Complaints]===
*When people, ready to switch to an e-cig, are severely restricted in terms of accessibility of nicotine-containing e-liquids, the success of e-cigs may be endangered. For the e-cig to be and remain successful, it is important that people have easy access to nicotine containing e-liquids.
*“In a series of controlled lab sessions with e-cig-naïve tobacco smokers, second-generation e-cigs were shown to be immediately and highly effective in reducing abstinence-induced cigarette craving and withdrawal symptoms, while not resulting in increases in eCO. Ad libitum use of e-cigs—in between and until six months after the lab sessions—resulted in remarkable reductions in or (biologically confirmed) complete abstinence from tobacco smoking in almost half of the participants who had no intention to quit smoking. Eight months after the start of the study 21% of all participants were completely abstinent from tobacco cigarettes. Similar reduction/cessation rates were obtained with guided versus non-guided switching to e-cigs. Part of the observed efficacy of e-cigs in this study may be related to the fact that they allowed to maintain relatively high blood nicotine levels and showed an excellent experienced benefits/complaints ratio, especially in comparison with continued tobacco smoking”...
*E-cigarette is an attractive long-term alternative and safer source of nicotine to conventional cigarette. Since their invention in 2003, there has been constant innovation and development of more efficient and appealing products. Here we show for the first time that second generation PVs can substantially decrease cigarette consumption without causing significant side effects in smokers not intending to quit. Moreover, overall participants’ perception and acceptance of these products was very good, in particular for those who quit or reduced smoking. Compared to our earlier work with first generation “cig-alikes”, technical problems and difficulties in use familiarization with second generation PVs were negligible. Improved products reliability and attractiveness might have contributed to the very low number of study failures and lost to follow-up and high success rates thus confirming the notion that these products are attractive substitutes for conventional cigarettes. Although large and carefully conducted RCTs will be required to confirm these preliminary encouraging observations, the notion that second generation PVs can substantially decrease cigarette consumption in smokers not intending to quit should be taken into consideration by regulatory authorities seeking to adopt proportional measures for the vapour category
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245610/pdf/ijerph-11-11220.pdf PDF Version]
*Citation: Adriaens K, Van Gucht D, Declerck P, Baeyens F. Effectiveness of the electronic cigarette: An eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11(11):11220-11248. Published 2014 Oct 29. doi:10.3390/ijerph111111220
*Acknowledgement: No external funding for this study was obtained.
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247211/ Success rates with nicotine personal vaporizers: a prospective 6-month pilot study of smokers not intending to quit]===
*Complete tobacco cessation is the best outcome for smokers, but the powerful addictive qualities of nicotine and of the ritualistic behavior of smoking create a huge hurdle, even for those with a strong desire to quit. Tobacco harm reduction (THR), the substitution of low-risk nicotine products for cigarette smoking, is a realistic strategy for smokers who have difficulty quitting. E-cigarettes are the newest and most promising products for THR. This approach has been recently exploited to reduce or reverse the burden of harm in smokers with mental health disorders and chronic airway disease.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247211/pdf/12889_2014_Article_7263.pdf PDF Version]
*Citation: Polosa R, Caponnetto P, Maglia M, Morjaria JB, Russo C. Success rates with nicotine personal vaporizers: a prospective 6-month pilot study of smokers not intending to quit. BMC Public Health. 2014;14:1159. Published 2014 Nov 8. doi:10.1186/1471-2458-14-1159
*Acknowledgement: The authors wish to thank FlavourArt. Authors wish to thank LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti Smoking League) for supporting this research.
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025024/ Characteristics, Perceived Side Effects and Benefits of Electronic Cigarette Use: A Worldwide Survey of More than 19,000 Consumers]===
*The main results of this survey indicate that ECs may be an effective substitute for smoking even in highly dependent subjects who are heavy smokers. Significant benefits are experienced by these people in physiologic functions and in some disease conditions, with former smokers (those who completely substituted smoking with EC use) being more likely to report such beneficial effects.
*Both former and current smokers initiated EC use with high nicotine-containing liquids. More than one-fifth of the population initiated use with more than 20 mg/mL nicotine concentration, with higher prevalence in former smokers, supporting the hypothesis that nicotine plays an important role in the success of ECs as smoking substitutes. This can be attributed to the lower nicotine absorption from EC use compared to smoking. Such repeated observations should be taken into consideration by the regulatory authorities.
*The most important reasons for participants to initiate ECs were to reduce or completely quit smoking and to reduce exposure of family members to second-hand smoking. It seems that these subjects are well-informed about the adverse health effects of smoking and are willing to try an alternative product which they consider less harmful.
*In conclusion, in this large sample of dedicated EC users, it seems that ECs are used as long-term substitutes to smoking. They can be effective even in subjects who are highly dependent on smoking and are heavy smokers. Mild temporary side-effects and significant benefits are reported by this population. Motivation for using ECs comes from their expected less harmful potential compared to smoking.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025024/pdf/ijerph-11-04356.pdf PDF Version]
*Citation: Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health. 2014;11(4):4356-4373. Published 2014 Apr 22. doi:10.3390/ijerph110404356
*Acknowledgement: The study was funded by a funding campaign of E-Cigarette Research Advocates Group, the owners of the website www.ecigarette-research.com. This is a non-profit group of electronic cigarette users with no relation to the electronic cigarette or other industry.
 
 
===2014: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511704/ Reasons for quitting cigarette smoking and electronic cigarette use for cessation help]===
*Thus, this may be the first study to suggest that smokers who want to quit smoking for immediate, extrinsic rewards may be attracted to use e-cigarettes to stop smoking cigarettes than smokers who want to quit smoking for intrinsic reasons such as health concerns. In conclusion, e-cigarettes appear to provide a “smoking” alternative to a section of cigarette smokers who may not quit smoking for health reasons. Public health efforts may need to consider employing e-cigarettes to promote tobacco-related harm reduction.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511704/pdf/nihms676311.pdf PDF Version]
*Citation: Pokhrel P, Herzog TA. Reasons for quitting cigarette smoking and electronic cigarette use for cessation help. Psychol Addict Behav. 2015;29(1):114-121. doi:10.1037/adb0000025
 
===2014: [https://academic.oup.com/ntr/article-abstract/17/2/245/1258995 Cigarette Users’ Interest in Using or Switching to Electronic Nicotine Delivery Systems (ENDS) for Smokeless Tobacco for Harm Reduction, Cessation, or Novelty: A Cross-Sectional Survey of US Adults]===
*This study highlights higher interest in ENDS versus smokeless tobacco and greater interest in both for harm reduction and cessation than due to novelty or smoking restrictions. Developing educational campaigns and informing practitioners about caveats around ENDS as cessation or harm reduction aids are critical.
*[https://sci-hub.st/10.1093/ntr/ntu103 PDF Version]
*Citation: Berg, C. J., Haardoerfer, R., Escoffery, C., Zheng, P., & Kegler, M. (2014). Cigarette Users’ Interest in Using or Switching to Electronic Nicotine Delivery Systems for Smokeless Tobacco for Harm Reduction, Cessation, or Novelty: A Cross-Sectional Survey of US Adults. Nicotine & Tobacco Research, 17(2), 245–255. doi:10.1093/ntr/ntu103
*Acknowledgement: This work was supported by the Centers for Disease Control and Prevention (3 U48 DP001909-04S1 to Principal Investigator (PI): CJB), the National Cancer Institute (U01CA154282-01 to PI: MK; 1K07CA139114-01A1 to PI: CJB), and the Georgia Cancer Coalition (PI: CJB).
 
 
===2013: [https://pubmed.ncbi.nlm.nih.gov/24029165/ Electronic cigarettes for smoking cessation: a randomised controlled trial]===
*657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis.
*At 6 months, verified abstinence was 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes
*[https://sci-hub.st/10.1016/S0140-6736(13)61842-5 PDF Version]
*Citation: Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, Williman J, Walker N. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013 Nov 16;382(9905):1629-37. doi: 10.1016/S0140-6736(13)61842-5. Epub 2013 Sep 9. PMID: 24029165.
*Acknowledgement: Funding: Health Research Council of New Zealand.
 
 
===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;10:19. Published 2013 Oct 4. doi:10.1186/1477-7517-10-19
 
 
===2013: [https://www.frontiersin.org/articles/10.3389/fpubh.2013.00056/full Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review]===
*When compared to the harmful effects of smoking, these studies suggest that vaping could be used as a possible “harm reduction” tool. There is evidence supporting e-cigarettes as an aide for smoking cessation, at least as successful as currently available FDA-approved NRTs.
*Citation: Palazzolo, D. L. (2013). Electronic Cigarettes and Vaping: A New Challenge in Clinical Medicine and Public Health. A Literature Review. Frontiers in Public Health, 1. doi:10.3389/fpubh.2013.00056
 
 
===2013: [https://academic.oup.com/ntr/article/15/10/1737/1183788 E-Cigarettes: Prevalence and Attitudes in Great Britain]===
*While we found evidence supporting the view that e-cigarette use may be a bridge to quitting, we found very little evidence of e-cigarette use among adults who had never smoked. British smokers would benefit from information about the effective use, risks, and benefits of e-cigarettes, as this might enable the use of e-cigarettes to improve public health.
*[https://scholar.google.com/scholar_url?url=https://academic.oup.com/ntr/article-pdf/15/10/1737/4005852/ntt057.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=5-niYKGiHo6RywT0wZbgCg&scisig=AAGBfm1x30ekBGwfhPgkxdJKFW0eOfPFPw PDF Version]
*Citation: Martin Dockrell, BA, Rory Morrison, BSc, Linda Bauld, PhD, Ann McNeill, PhD, E-Cigarettes: Prevalence and Attitudes in Great Britain, Nicotine & Tobacco Research, Volume 15, Issue 10, October 2013, Pages 1737–1744, doi: 10.1093/ntr/ntt057
*Acknowledgements: Fieldwork was supported by Action on Smoking and Health and members of the Smokefree Action Coalition. Linda Bauld and Ann McNeill are members of the UK Centre for Tobacco Control Studies. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council (ESRC), the Medical Research Council (MRC), and the National Institute for Health Research (NIHR), under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged.
 
 
===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691171/ EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as Tobacco Cigarettes Substitute: A Prospective 12-Month Randomized Control Design Study]===
*In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects. In view of the fact that subjects in this study had no immediate intention of quitting, the reported overall abstinence rate of 8.7% at 52-week was remarkable.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691171/pdf/pone.0066317.pdf PDF Version]
*Citation:Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study [published correction appears in PLoS One. 2014;9(1). doi:10.1371/annotation/e12c22d3-a42b-455d-9100-6c7ee45d58d0]. PLoS One. 2013;8(6):e66317. Published 2013 Jun 24. doi:10.1371/journal.pone.0066317
*Acknowledgement: This research was supported by a grant-in-aid from Lega Italiana AntiFumo.
 
 
===2013: [https://pubmed.ncbi.nlm.nih.gov/23551515/ 'Vaping' profiles and preferences: an online survey of electronic cigarette users]===
*Seventy-four percent of participants reported not smoking for at least a few weeks since using the e-cigarette and 70% reported reduced urge to smoke. *Seventy-two percent of participants used a 'tank' system, most commonly. Mean duration of use was 10 months. Only 1% reported exclusive use of non-nicotine containing liquid. E-cigarettes were generally considered to be satisfying to use; elicit few side effects; be healthier than smoking; improve cough/breathing; and be associated with low levels of craving. Among ex-smokers, 'time to first vape' was significantly longer than 'time to first cigarette' suggesting a lower level of dependence to e-cigarettes. Ex-smokers reported significantly greater reduction in craving than current smokers.
*E-cigarettes are used primarily for smoking cessation, but for a longer duration than nicotine replacement therapy, and users believe them to be safer than smoking
*[https://sci-hub.st/10.1111/add.12150 PDF Version]
*Citation: Dawkins, L., Turner, J., Roberts, A., & Soar, K. (2013). “Vaping” profiles and preferences: an online survey of electronic cigarette users. Addiction, 108(6), 1115–1125. doi:10.1111/add.12150
*No funding was received for this study. The first author has a collaborative relationship with the Electronic Cigarette Company (TECC) and Totally Wicked E-Liquids (TWEL), and has received funds from these companies to attend academic conferences. TECC and TWEL reviewed and approved the content of the questionnaire and set up links from their websites to the host site at UEL.
 
 
===2012: [https://www.sciencedirect.com/science/article/abs/pii/S0306460312000913 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
*Acknowledgement: 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.
 
 
===2011: [https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-585 Successful smoking cessation with electronic cigarettes in smokers with a documented history of recurring relapses: a case series]===
*The most important message from this case series is that these smokers, with a documented history of recurring relapses, were able to quit smoking and to remain abstinent for at least six months after taking up an electronic cigarette.
*[https://jmedicalcasereports.biomedcentral.com/track/pdf/10.1186/1752-1947-5-585.pdf PDF Version]
*Citation: Caponnetto, P., Polosa, R., Russo, C. et al. Successful smoking cessation with electronic cigarettes in smokers with a documented history of recurring relapses: a case series. J Med Case Reports 5, 585 (2011). https://doi.org/10.1186/1752-1947-5-585
 
 
===2011: [https://pubmed.ncbi.nlm.nih.gov/21989407/ Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study]===
*Sustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day.
*The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203079/pdf/1471-2458-11-786.pdf PDF Version]
*Citation: Polosa R, Caponnetto P, Morjaria JB, Papale G, Campagna D, Russo C. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011 Oct 11;11:786. doi: 10.1186/1471-2458-11-786. PMID: 21989407; PMCID: PMC3203079.
*Acknowledgement: We wish to thank Arbi Group Srl (Milano, Italy) for the free supplies of ‘Categoria’ e-Cigarette kits and nicotine cartridges. None of the authors have any competing interests to declare, but RP has received lecture fees from Pfizer and, from Feb 2011, he has been serving as a consultant for Arbi Group Srl.Arbi Group Srl (Milano, Italy), the manufacturer of the e-Cigarette supplied the product, and unrestricted technical and customer support. They were not involved in the study design, running of the study or analysis and presentation of the data.
 
 
===2011: [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2011.03505.x Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy]===
*Almost all (97%) used e‐cigarettes containing nicotine.
*Most (96%) said the e‐cigarette helped them to quit smoking or reduce their smoking (92%).
*Reasons for using the e‐cigarette included the perception that it was less toxic than tobacco (84%), to deal with craving for tobacco (79%) and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%).
*Most ex‐smokers (79%) feared they might relapse to smoking if they stopped using the e‐cigarette.
*Users of nicotine‐containing e‐cigarettes reported better relief of withdrawal and a greater effect on smoking cessation than those using non‐nicotine e‐cigarettes.
*[https://sci-hub.se/10.1111/j.1360-0443.2011.03505.x PDF Version]
*Citation: Etter, J.-F., & Bullen, C. (2011). Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy. Addiction, 106(11), 2017–2028. doi:10.1111/j.1360-0443.2011.03505.x
 
 
===2011: [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1742-1241.2011.02751.x Electronic cigarettes (e‐cigs): views of aficionados and clinical/public health Perspectives]===
*The health risks from smoking are large and are known with certainty. Comparatively, the health risks from e‐cig use are likely much smaller (if any) and temporarily switching to e‐cigs will likely yield a large health benefit.
*If the patient perceives that the e‐cig is helping them to stay off cigarettes and is not reporting any health problems likely attributable to the e‐cig, then the focus should be on staying smoke‐free rather than e‐cig free.
*[https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-1241.2011.02751.x PDF Version]
*Citation: Foulds, J., Veldheer, S., & Berg, A. (2011). Electronic cigarettes (e-cigs): views of aficionados and clinical/public health perspectives. International Journal of Clinical Practice, 65(10), 1037–1042. doi:10.1111/j.1742-1241.2011.02751.x 
 
 
===2011: [https://www.sciencedirect.com/science/article/abs/pii/S0749379710007920 Electronic Cigarettes As a Smoking-Cessation Tool: Results from an Online Survey]===
*A large percentage of respondents reported a reduction in the number of cigarettes they smoked (66.8%) and almost half reported abstinence from smoking for a period of time (48.8%). Those respondents using e-cigarettes more than 20 times per day had a quit rate of 70.0%. Of respondents who were not smoking at 6 months, 34.3% were not using e-cigarettes or any nicotine-containing products at the time.
*The distinct and unique advantage of e-cigarettes is that they allow individuals to utilize one device that can simultaneously address nicotine withdrawal, psychological factors, and behavioral cues that serve as barriers to smoking abstinence.
*[https://sci-hub.se/10.1016/j.amepre.2010.12.006 PDF Version]
*Citation: Siegel, M. B., Tanwar, K. L., & Wood, K. S. (2011). Electronic Cigarettes As a Smoking-Cessation Tool. American Journal of Preventive Medicine, 40(4), 472–475. doi:10.1016/j.amepre.2010.12.006
 
 
===2011: [https://academic.oup.com/ntr/article/13/9/860/1134354 Interviews With “Vapers”: Implications for Future Research With Electronic Cigarettes]===
*Experienced users report health gains typical for smoking cessation despite continued vaping.
*There were pervasive themes including the language and culture of vaping; social and informational support among vapers, motives and perceived benefits of using e-cigs versus cigarettes including cigarette-like enjoyment, cost, restored sense of taste and smell, and improved breathing and exercise tolerance; rapidly reduced nicotine tolerance and dependence; and a strong interest in e-cig–related research and policy.
*[https://sci-hub.se/10.1093/ntr/ntr088 PDF Version]
*Citation: McQueen, A., Tower, S., & Sumner, W. (2011). Interviews With “Vapers”: Implications for Future Research With Electronic Cigarettes. Nicotine & Tobacco Research, 13(9), 860–867. doi:10.1093/ntr/ntr088
*Acknowledgement: This research was conducted independent of grant funding. AM is supported by a Mentored Research Scientist Grant from the American Cancer Society (CPPB-113766).
 
 
===2010: [https://tobaccocontrol.bmj.com/content/19/2/98 Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial]===
*Conclusions “The 16 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence, was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette. Evaluation of the ENDD for longer-term safety, potential for long-term use and efficacy as a cessation aid is needed.”
*[https://sci-hub.se/10.1136/tc.2009.031567 PDF Version]
*Citation: Bullen, C., McRobbie, H., Thornley, S., Glover, M., Lin, R., & Laugesen, M. (2010). Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tobacco Control, 19(2), 98–103. doi:10.1136/tc.2009.031567
*Acknowledgement: This project was funded by Ruyan Group (Holdings) Limited, Beijing and Hong Kong, via Health New Zealand Ltd. The study sponsors supplied the ENDDs used in the trial and funded the trial. The Clinical Trials Research Unit contracted with Health New Zealand Ltd to conduct the trial, independently of Ruyan Group (Holdings) Ltd. The trial design conduct, analysis and interpretation of results were conducted independently of the sponsors.
 
 
===2010: [https://link.springer.com/article/10.1186/1471-2458-10-231 Electronic cigarettes: a survey of users]===
*Our results suggest that ecigarettes are used mainly to quit smoking, and may be useful for this purpose.
*[https://link.springer.com/content/pdf/10.1186%2F1471-2458-10-231.pdf PDF Version]
*Citation: Etter, JF. Electronic cigarettes: a survey of users. BMC Public Health 10, 231 (2010). https://doi.org/10.1186/1471-2458-10-231
 
 
===2006: [https://tobaccocontrol.bmj.com/content/15/3/210 Role of snus in initiation and cessation of tobacco smoking in Sweden]===
*Use of snus in Sweden is associated with a reduced risk of becoming a daily smoker, and increased likelihood of stopping smoking
*Citation: Ramström LM, Foulds JRole of snus in initiation and cessation of tobacco smoking in Sweden, Tobacco Control 2006;15:210-214.
*Acknowledgement: LR owns shares in Pfizer Inc, and both he and JF have done paid consultancy work for Pfizer Inc and other agencies involved in public health. LR has periodically been employed as short term consultant with WHO and JF has provided testimony for plaintiffs in law suits against tobacco companies. None of the authors has received any financial support from the tobacco industry.
 
 
===2005: [https://tobaccocontrol.bmj.com/content/14/6/422 Is Swedish snus associated with smoking initiation or smoking cessation?]===
*“Among males participating in a large population based twin study in Sweden, snus use was associated with smoking cessation but not initiation.”
*[https://tobaccocontrol.bmj.com/content/tobaccocontrol/14/6/422.full.pdf PDF Version]
*Citation: Furberg H, Bulik CM, Lerman C, et alIs Swedish snus associated with smoking initiation or smoking cessation?Tobacco Control 2005;14:422-424.
*Acknowledgement: This work was supported by CA-085839 to PFS
<br>
<br>
<br>


==Spinal Cord Injury==
='''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]===  
===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
*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 [[Abbreviations|'''spinal cord injury (SCI)''']].
*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 [[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.
*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]
*[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
*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.
*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
*Key words: spinal cord injury; nicotine; neuronal nicotinic receptors; oxidative stress; inflammatory responses; nitric oxide synthase
<br>


 
='''Tourette's Syndrome'''=  
 
===2012 [https://pubmed.ncbi.nlm.nih.gov/22776623/ Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond]===  
==Tourette Syndrome==
 
 
===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.
* 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 summarizes the studies on the behavioral biology of the basal ganglia and its neurotransmitters.
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*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.  
*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]===  
===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.  
*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.
*Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention.
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*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.  
*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]===  
===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  
*[[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]
*[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.
*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]===  
===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.
*Within 24 hr of the application of a single 7-mg [[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.
*Application of a 7-mg TNP to children and adolescents with [[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]
*[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.
*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.
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*Keywords: Nicotine; Tourette's syndrome; tics; neuropsychiatric disorders
*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?]===  
===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)''']].
*nicotine may have therapeutic uses in the treatment of [[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.
*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]
*[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.
*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]===  
=== 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.
* 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 [[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 [[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
*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]
*[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.
*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]===  
===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.
*In this study, nicotine markedly potentiated haloperidol effects in treating [[Abbreviations|'''TD''']], and showed lesser effects on TD when used alone.
*[https://sci-hub.st/10.1016/0006-3223(92)90315-q PDF Version]
*[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.
* 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.
*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.


 
===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===  
===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
*When chronically taken, nicotine may result in: protection against Tourette's disease (other diseases mentioned in study)
*When chronically taken, nicotine may result in: protection against Tourette's disease (other diseases mentioned in study)
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
*[https://sci-hub.st/10.1111/j.1360-0443.1991.tb01810.x PDF Version]
Line 1,294: Line 1,256:
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
*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://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]===  
===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.
*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]
*[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.
*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.
*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.
<br>


==Weight Loss / Appetite Control / Metabolism / Obesity==
='''Weight Loss / Appetite Control / Metabolism / Obesity'''=
===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.
*Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
*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


===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===
===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===  
* When chronically taken, nicotine may result in reduction of body weight
* 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]
*[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.
*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.
*Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.
<br>
='''Suggested additions to this page'''=
===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: Implications for neurodegenerative diseases]===
===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]===
=== 2023: Twitter thread on nicotine benefits [https://twitter.com/MichaelChampla1/status/1693086186087010351?s=20 here] ===
* thread of studies / benefits
===2023: [https://medium.com/@thechinaacademy/nicotine-reduces-mortality-rate-by-40-8864335940cf Nicotine reduces mortality rate by 40%]===
*Article about a mouse study
=== 2014 [http://journals.cambridge.org/abstract_S1834261214000279 Nicotine: Pharmacology, Toxicity and Therapeutic use] ===
* Karl Fagerström. Journal of Smoking Cessation, 9, pp 53-59 doi:10.1017/jsc.2014.27
* May need a new heading: general therapeutic use
===2023: [https://pubmed.ncbi.nlm.nih.gov/37208927/ Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===
===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]===
===[https://pubmed.ncbi.nlm.nih.gov/?term=Mundel+nicotine Mundel nicotine search - exercise/athletics]===
===[https://pubmed.ncbi.nlm.nih.gov/?term=Zandonai+nicotine Zandonai nicotine search exercise/athletics]===
===2023: [https://drive.google.com/file/d/1ofdbKWq6rIBxI8vQAzjV8z-TYoacrqKB/view Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===
===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]===
=== 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.] ===
* Information on how nicotine is protective, technical.
* 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.
* Carvajal-Oliveros A, Dominguez-Baleón C, Sánchez-Díaz I, Zambrano-Tipan D, Hernández-Vargas R, Campusano JM, Narváez-Padilla V, Reynaud E. PLoS One. 2023 Mar 1;18 PMID: 36857384
===2023 [https://www.sciencedirect.com/science/article/pii/S027869152300039X?via%3Dihub Tobacco heating system has less impact on bone metabolism than cigarette smoke]===
===2023 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9849855/ Effect of nicotine on cholesterol gallstone formation in C57BL/6J mice fed on a lithogenic diet]===
=== 2022: [https://assets.researchsquare.com/files/rs-1062121/v1/fb8f5195-4cce-470f-9e09-e752fae3c931.pdf?c=1642705044 Part One: Abuse Liability of Vuse Solo Relative To Combustible Cigarettes And Nicotine Gum] ===
=== 2014: [https://link.springer.com/chapter/10.1007/978-1-4939-1167-7_20 Nicotinic Receptors and Mental Illness] ===
===2021: [https://pubmed.ncbi.nlm.nih.gov/34757527/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
*Animal
===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]===




*mouse study


==Suggested studies to add to this page==
===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===  


===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===


*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://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]===
===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
 
===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===
 
===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===


===2021: [[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?]===  


===[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]===
===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%.
*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]
*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]


===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]===
===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===
 
===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]===
===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===


===Dr. Newhouse [http://mindstudy.org/news Mind Study]===
=== 2021: [https://www.spektrum.de/news/kognition-nikotin-gegen-neuropsychiatrische-erkrankungen/1924141 Kognition: Nikotin gegen neuropsychiatrische Erkrankungen] (German)  'Cognition: nicotine versus neuropsychiatric disorders' ===


===[https://journals.sagepub.com/doi/abs/10.1177/0883073820974851?journalCode=jcna Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===
===Dr. Newhouse [http://mindstudy.org/news Mind Study]===  


===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
===[https://journals.sagepub.com/doi/abs/10.1177/0883073820974851?journalCode=jcna Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants]===  


===[https://pubmed.ncbi.nlm.nih.gov/32595653/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===
===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.


===[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592351/ Targeting the “Cytokine Storm” for Therapeutic Benefit]===
===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]===  


===Fluharty et al (2016). [https://pubmed.ncbi.nlm.nih.gov/27199385/ The association of cigarette smoking with depression and anxiety: a systematic review.] Nicotine & Tobacco Research===
===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===  
*“The literature on the prospective association between smoking and depression and anxiety is inconsistent in terms of the direction of association most strongly supported. This suggests the need for future studies that employ different methodologies, such as Mendelian randomization. . . . Two studies that have used [Mendelian randomization] have found no evidence to support a causal association between smoking and depression and anxiety, while another found evidence to suggest that smoking was associated with lower odds of depression during pregnancy.”


===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.


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


===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://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===  


2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530045/ Caffeine intake and Cognitive Functions in Children] For comparison effects of caffeinated products


===[https://docs.google.com/document/d/13-D2q1P0KpmZuoFBkKV4l9wUEQ-zcHfp6MAVJGoAaG4/edit?usp=sharing INNCO's List smoking cessation]===
='''More Information'''=  
Started: continue @ “Long-term use of e-cigarettes was associated with a higher rate of quitting smoking.”
https://tobaccocontrol.bmj.com/content/25/Suppl_1/i90.full




*[[Special:MyLanguage/Nicotine Studies|'''List of researchers''']] studying nicotine / tobacco harm reduction


===[https://twitter.com/jkelovuori/status/1413963688709664769 Go through the links in this thread]===


==More Information==
*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.
*[[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.'''
*'''PAGE EDITORS - Please only add Studies, Surveys, Papers in this format to keep page consistent for all viewers.'''

Latest revision as of 18:25, 20 March 2024


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.

Nicotine Therapeutic benefits banner




Note: Some topics are subgroups under the main topic of "Mental Health."

Acne

2010 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 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 Does smoking influence acne?

  • 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

2018 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.
  • 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: 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: 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.
  • 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 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 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 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 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.
  • 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.

2007 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: Smoking to self-medicate attentional and emotional dysfunctions

  • (Note: Need to add summary)

2006 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 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.
  • 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.

2003: 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 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 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 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.
  • 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 (K02MH00981–02) to Dr. March

1996 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.
  • 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: 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.


Addiction / Abuse Liability / Dependence (Nicotine)

2021 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use

  • Among US high school students, increases in the prevalence of nicotine product use from 2012 to 2019 do not appear to have been accompanied by a similar increase in the population burden of nicotine dependence. This may be at least partly attributable to a shift in the most common product of choice from cigarettes (on which users are most dependent) to e-cigarettes (on which users are least dependent).
  • PDF Version
  • Citation: Jackson, S. E., Brown, J., and Jarvis, M. J. (2021) Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use. Addiction, 116: 1859– 1870. doi: 10.1111/add.15403
  • Acknowledgement: Cancer Research UK (C1417/A22962) supported S.J. andJ.B.’s salaries.

2020 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

2020 Dependence and Use Characteristics of Adult JUUL Electronic Cigarette Users

2020 A comparison of product dependence among cigarette only, ENDS only, and dual users: Findings from Wave 3 (2015-2016) of the PATH study

2020 Dependence on e-cigarettes and cigarettes in a cross-sectional study of US adults

2019 Changes in E-Cigarette Use Behaviors and Dependence in Long-term E-Cigarette Users

2018 Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum

  • These findings are concordant with our previous results and provide evidence that menthol Vuse Solo ECs have abuse liability that is lower than menthol cigarettes and potentially greater than that of nicotine gum.
  • PDF Version
  • Citation: Stiles MF, Campbell LR, Jin T, Graff DW, Fant RV, Henningfield JE. Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum. Psychopharmacology (Berl). 2018 Jul;235(7):2077-2086. doi: 10.1007/s00213-018-4904-x. Epub 2018 May 3. PMID: 29725702; PMCID: PMC6015619.
  • Acknowledgement: ClinicalTrials.gov identifier: NCT02664012. MF Stiles, LR Campbell, and T Jin are full-time employees of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc. DW Graff is a full-time employee of Celerion and provided the original draft of the manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on smoking cessation and tobacco harm minimization (including nicotine replacement therapy and electronic vapor products) to Niconovum, USA, Inc., RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.). JE Henningfield also owns an interest in intellectual property for a novel nicotine medication. Through PinneyAssociates, Fant and Henningfield provide consulting services to pharmaceutical companies on abuse potential assessment, and the regulation of substances with a potential for abuse.

2017 A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study

2015 Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users

2015 Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes

2013 Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

  • We also note that although any nicotine-containing product has the potential to be addicting, based on the available evidence, currently marketed OTC NRT products do not appear to have significant potential for abuse or dependence. A 2010 review of historical reports made to the Agency's Adverse Event Reporting System and to the Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network between 1984 and 2009 suggested that NRT products have a low potential for abuse. Several published studies have also found that the abuse liability and dependence potential of NRT products is low, especially compared to cigarettes.
  • PDF Version
  • Citation: Food and Drug Administration, 78 FR 19718

2012 Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence

  • More recently, it has been found that, although nicotine is the most important addictive component of tobacco smoke, it is probably not the only substance involved in the development of tobacco dependence. In light of what is now known about what determines cigarette smoking, it seems timely to propose a renaming of the Fagerstrom Test for Nicotine Dependence (FTND) to the Fagerstrom Test for Cigarette Dependence (FTCD).
  • PDF Version
  • Citation: Karl Fagerström, Ph.D., Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence, Nicotine & Tobacco Research, Volume 14, Issue 1, January 2012, Pages 75–78, doi: 10.1093/ntr/ntr137
  • See Also: 2013: Dependence on tobacco and nicotine

2003 Subjective effects of the nicotine lozenge: assessment of abuse liability

  • Results suggest that the nicotine lozenge has low abuse liability, both in adults and young adults.
  • PDF Version
  • Citation: Houtsmuller EJ, Henningfield JE, Stitzer ML. Subjective effects of the nicotine lozenge: assessment of abuse liability. Psychopharmacology (Berl). 2003 Apr;167(1):20-7. doi: 10.1007/s00213-002-1361-2. Epub 2003 Mar 4. PMID: 12616334.
  • Acknowledgement: This research was supported by SmithKline Beecham Consumer Healthcare.

2002 Flavor improvement does not increase abuse liability of nicotine chewing gum

  • 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).
  • PDF Version
  • Citation: Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacol Biochem Behav. 2002 Jun;72(3):559-68. doi: 10.1016/s0091-3057(02)00723-2. PMID: 12175452.
  • Acknowledgement: This study was supported by SmithKline Beecham Consumer Healthcare.


Addiction (Nicotine with the use or abuse of recreational substances)

2021 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.


Allergies / Hayfever / Histamines

2017: 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.
  • Acknowledgements: 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).

2009: Nicotine Primarily Suppresses Lung Th2 but not Goblet Cell and Muscle Cell Responses to Allergens

  • Animal Study
  • These 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: Mishra NC, Rir-Sima-Ah J, Langley RJ, et al. Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol. 2008 Jun 1;180(11):7655-63. doi: 10.4049/jimmunol.180.11.7655. PMID: 18490768; PMCID: PMC2614131.

Acknowledgments: This work was supported in part by grants from the National Institutes of Health (RO1 DA017003, R01 DA04208-15, and RO1DA042087S).

2004: The effect of nicotine on basophil histamine release

  • This study has demonstrated that nicotine agonists inhibit histamine release from human basophils.
  • 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)

2013 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.
  • 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 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.
  • 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 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.
  • 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

2002 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.
  • 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 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 Does nicotine have beneficial effects in the treatment of certain diseases?

  • nicotine may have therapeutic uses in the treatment of 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.
  • 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 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).
  • 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 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)
  • 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 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.
  • 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.


Aphthous ulcers

2015 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.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387635/?report=printablePrintable Version
  • 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.

2011 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.
  • PDF Version
  • 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

2002 Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine

  • NOTE: Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that less people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine.
  • 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.
  • 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 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.
  • 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

1991 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.
  • 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

2023: Tobacco heating system has less impact on bone metabolism than cigarette smoke

  • We found that, following acute or chronic exposure, particulate matter extract from the aerosol of an HTP, the Tobacco Heating System (THS), was less harmful to the bone coculture system than reference cigarette (1R6F) smoke extract. In the fracture healing model, cultures exposed to the THS extract maintained similar osteoclast activity and calcium deposits as control cultures. Conversely, smoke extract exposure promoted osteoclast activity, resulting in an osteoporotic environment, whose formation could be prevented by bisphosphonate coadministration. Thus, THS is potentially less harmful than cigarette smoke to bone cell differentiation and bone mineralization - both being crucial aspects during the reparative phase of fracture healing.
  • Comment From Clive Bates: "A characteristically cautious statement. But still annoying as it gives no sense of the magnitude of "less harmful".  I realise this is not a straightforward idea (see paper), but the harm reduction proposition is necessarily quantitative, even if expressed in pseudo-quantitative terms. If they want the harm reduction proposition to succeed these industries need to develop evidence-based metrics for communicating risk reduction.  Eg. it required xx times the exposure to vape liquids to have the same effect as tobacco smoke."
  • Cell/organoid study
  • Note: tobacco industry funded (PMI)
  • Weng W, Bovard D, Zanetti F, Ehnert S, Braun B, Uynuk-Ool T, Histing T, Hoeng J, Nussler AK, Aspera-Werz RH. Food Chem Toxicol. 2023 Jan 25:113637. doi: 10.1016/j.fct.2023.113637. Online ahead of print. PMID: 36708864

Auditory

2021 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.
  • 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 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.
  • 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.

Atopic Dermatitis

2023: Association of Atopic Dermatitis with Substance Use Disorders: A Case-Control Study in the All of Us Research Program.

  • Joshi TP, Bancroft A, DeLeon D, Garcia D, Kunisetty B, Truong P, Kim SJ. J Am Acad Dermatol. 2023 Jul 14:S0190-9622(23)01361-0. doi: 10.1016/j.jaad.2023.06.051. Online ahead of print. PMID: 37454697 No abstract available.
  • Patients with AD, compared to controls, were more likely to use cannabis (4.4% vs 2.7%, 60 P <0.01), hallucinogens (3.2% vs 1.8%, P <0.01), opioids (3.5% vs 1.3%, P <0.01), and 61 stimulants (2.3% vs 1.5%, P <0.01) and less likely to use e-cigarettes (10.8% vs 15.6%, P <0.01) 62 and regular cigarettes (39.0% vs 56.0%, P <0.01).
  • In multivariable analysis adjusted for age, 63 income, insurance type, race, sex, depression, and anxiety, only the associations with cannabis 64 (aOR 1.49, 95% CI 1.24-1.80), e-cigarette (aOR 0.71, 95% CI 0.65-0.77), and regular cigarette 65 use (aOR 0.65, 95% CI 0.63-0.68) persisted (Table I)

Autism

2020: The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model

  • 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.
  • Mouse study, may not explain human response
  • Autism Research 2020 Aug;13(8):1311-1334 doi: 10.1002/aur.2342. Epub 2020 Jul 21.

2018 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 transdermal nicotine (TN/TNP) in a small sample of adults with severe 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.
  • 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).
  • Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep


Behcet's disease

2010 Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series

  • In this report, we describe five ex-smoker 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.
  • PDF Version
  • 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
  • Keywords: Behçet’s disease, Cigarette smoking, Nicotine therapy, Mucocutaneous lesions

2000 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.
  • 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 Injury / Disease

2004 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.
  • 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.
  • KEYWORDS: nicotine; neurodegeneration; neuroprotection


Cancer / Cancer Treatments

2020 Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells

  • Nicotine inhibits ovarian cancer cell ERK and p38 MAPK signaling.
  • Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
  • 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.
  • Keywords: Nicotine, Ovarian cancer, Spheroid, MAPK, Invasion

2013 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 nAChR modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
  • 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.
  • Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy


Cannabis / THC

2020 Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial

  • The findings provide the first evidence that 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.
  • 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.


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. Source: US CDC

2013 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

2023: 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 | https://doi.org/10.3389/fnins.2023.1252705
  • 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: 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: Molecular insights into the benefits of nicotine on memory and cognition

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

2020 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.
  • 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: 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 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.
  • 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.

2016: 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: 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.
  • PDF Version

2012: 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.
  • 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.

2003 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.
  • 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 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 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 (IQ).
  • In this experiment we used the Raven 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.
  • 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 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.
  • 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)

2023: 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: 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: 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

2020 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 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: 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: 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

2022 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.
  • 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.
  • 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

2011 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.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • 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

2008 Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study

  • Smoking has a detrimental effect in Crohn's disease (CD), but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits 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.
  • 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 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.
  • PDF Version
  • 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.

1999 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.
  • 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.
  • Keywords: enemas, nicotine, transdermal patches, ulcerative colitis

1996 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.
  • 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 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.
  • 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 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against ulcerative colitis (other diseases mentioned in study)
  • 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: 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 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.
  • 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.


Endurance / Exercise / Athletic Performance

2006 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.
  • PDF Version
  • Mündel, T. and Jones, D.A. (2006), Effect of transdermal nicotine administration on exercise endurance in men. Experimental Physiology, 91: 705-713. doi: 10.1113/expphysiol.2006.033373


HIV/AIDS

2022: Tobacco Harm Reduction with Vaporised Nicotine (THRiVe): A Feasibility Trial of Nicotine Vaping Products for Smoking Cessation Among People Living with HIV

  • This study found that the provision of NVPs for 12 weeks was associated with 7-day point prevalence tobacco smoking abstinence among 35% of a sample of PLHIV who smoked tobacco daily. These findings suggest that NVPs represent a potentially feasible and effective short-to-medium term tobacco smoking cessation aid and/or tobacco harm reduction strategy among PLHIV.


Huntington’s Disease

2005: 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.
  • 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.


Inflammation

2023: 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.

2022 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.
  • 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.
  • 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

2021: 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 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 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.

2016 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 EAE mice via multiple 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.
  • 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: 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 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 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 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 MS therapy.
  • 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.

2012 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.
  • 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 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.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • 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

2011 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.
  • PDF Version
  • Funding: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).
  • 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

2011 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.
  • PDF Version
  • 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 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 spinal cord injury (SCI).
  • The results of the present study indicate that 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.
  • 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.

2006 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 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


Mental Health

  • See subcategories below


Mental Health - Anxiety

2016: 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


Mental Health - Behavior Issues

  • See Also: ADD/ADHD above

2020 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 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.
  • 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.).
  • Keywords: Nicotine, Nicotinic receptor, Aggression, Aggressive behavior, Impulsivity, Acetylcholine

2018 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 transdermal nicotine (TN/TNP) in a small sample of adults with severe 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.
  • 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).
  • Keywords: Nicotine; nicotinic acetylcholine receptor; autism spectrum disorder; aggression; irritability; adult; sleep


Mental Health - Depression

2022: 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 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: 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

2000 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.
  • 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 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.
  • 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 Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder

  • In 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.
  • 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 Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Non-Smokers with Late-Life Depression

  • 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.
  • 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 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.
  • 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 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 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 FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
  • 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 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.
  • 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 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 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 Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.

1995 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
  • 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 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.
  • 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 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)
  • 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 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 Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review

  • Nicotine may ameliorate OC symptoms in severe, treatment-refractory OCD patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
  • 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 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.
  • 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

2022 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.
  • Twitter thread about this study
  • 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).
  • 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

2021 A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes

  • A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking. Further research with a larger sample and a comparator group is needed.
  • PDF Version
  • Citation: Pasquale Caponnetto, PhD, Jennifer DiPiazza, PhD, Jason Kim, MD, Marilena Maglia, Lyc Psych, Riccardo Polosa, MD, PhD, A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes, Nicotine & Tobacco Research, Volume 23, Issue 7, July 2021, Pages 1113–1122, 10.1093/ntr/ntab005
  • Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.

2020 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 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.
  • 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.
  • Keywords: Schizophrenia, Nicotine, Cognition, Early sensory

2017: Nicotine reverses hypofrontality in animal models of addiction and schizophrenia

  • Ultimately the authors of the study, published in the journal Nature Medicine, envision their work could lead to new non-addictive, nicotine-based treatments for some of the 51 million people worldwide who suffer from the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.
  • “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.
  • Note: Mouse study; using a model known to mimic human disease.
  • 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.
  • 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)

2016: 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

2009 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.
  • 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.

2002 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 Role for the nicotinic cholinergic system in movement disorders; therapeutic implications

  • Animal Study
  • Several 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.
  • 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

2023: Oral Tobacco Use Linked to Slower MS Progression

  • Jing Wu, Tomas Olsson, Jan Hillert, Lars Alfredsson, Anna Karin Hedström
  • Corresponding author Jing Wu, Karolinska Institute, 171 77 Stockholm, Stockholm, Sweden; Email: jing.wu [at] ki.se [Please demangle the email address; spam prevention ed.]
  • Full Text
  • Oral tobacco use, also known as moist snuff, is associated with slower progression of multiple sclerosis (MS), a new study shows.
  • Jing Wu, PhD candidate "Our finding that snuff use is not associated with worse disease progression indicates that nicotine replacement therapy could be an attractive way to increase the chance of quitting smoking post diagnosis,"
  • To investigate, the researchers analyzed data from 9089 patients with MS who were participants in two case-control studies from the Swedish MS registry, mean age 37.6 years and 72% female. At baseline, current cigarette smokers had significantly higher Expanded Disability Status Scale (EDSS) scores compared with nonsmokers.
  • All analyses controlled for age at diagnosis, sex, disease phenotype, disease duration, baseline EDSS, and use of disease-modifying therapy.
  • Compared with never smoking, current smoking was associated with an increased risk of clinical disease worsening (CDW) (adjusted hazard ratio [aHR] 1.13; 95% CI 1.06-1.21), of reaching EDSS 3 (aHR 1.21, 95% CI 1.09-1.34), and EDSS 4 (aHR 1.31, 95% CI 1.14-1.51). In addition, compared with never smokers, current smoking was associated with a higher risk of physical and psychological worsening as determined by the MS Impact Scale-29 (MSIS-29), and worsening cognitive performance measured by the Symbol Digit Modalities Test (SDMT).
  • The study revealed a dose-dependent relationship between smoking and negative MS-related outcomes.
  • Current snuff use was significantly associated with lower risk of reaching EDSS 4 (aHR 0.73, 95% CI 0.58-0.92), but not CDW or EDSS 3. It was not significantly associated with the risk of worsening health-related quality of life or cognition.
  • In a perplexing turn of events study co-author Anna Karin Hedström, MD, PhD said "Physicians should not recommend smoking MS patients switch to snuff, as snuff may have other negative health consequences." [Why not? if the alternative is continued smoking? ed.] Particularly considering she also said this "This indicates that nicotine is not the substance that leads to worse prognosis and that nicotine replacement therapy is probably harmless — at least with respect to disease progression."

2016 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 EAE mice via multiple 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.
  • 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: MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease

2014 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 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.
  • 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 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 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 MS therapy.
  • 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.


Narcolepsy

2021: The therapeutic use of medical nicotine in narcolepsy

2012: Narcolepsy with Cataplexy Masked by the Use of Nicotine

2010: A Novel Approach to Treating Morning Sleep Inertia in Narcolepsy


Oral / Jaw

2021: 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 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.
  • 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 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

2023: 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 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

2020 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.
  • 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 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.
  • 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 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 nAChR modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
  • 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.
  • Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy

2011 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.
  • 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 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 RRP in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
  • 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

2002 Isoflurane hyperalgesia is modulated by nicotinic inhibition

  • Animal study
  • Female mice had significant hyperalgesia from 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

2024: Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease

  • 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.) Paper on the UPS and it's purpose for info.
  • Exp Brain Res. 2024 Mar 2. Inam Ullah, Shahab Uddin, Longhe Zhao, Xin Wang, Hongyu Li. PMID: 38430248 DOI: 10.1007/s00221-023-06765-9
  • Animal study (worms with humanised neurons)

2023: 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.
  • Front. Aging Neurosci., 13 September 2023 Sec. Parkinson’s Disease and Aging-related Movement Disorders Volume 15 - 2023 | https://doi.org/10.3389/fnagi.2023.1223310

2023: Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.

  • 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.
  • Mouse study
  • Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. eCollection 2023. PMID: 36817162 Free PMC article.

2023: Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune

  • You have to dig into text and tables to spot “Parkinson disease risk was substantially lower among Black veterans and EVER-SMOKERS (OR 0.49, 95% CI: 0.40-0.61).
  • That is a huge benefit that is seemingly not followed up, but probably should be.
  • Samuel M. Goldman, MD, MPH; Frances M. Weaver, PhD; Kevin T. Stroupe, PhD; et al JAMA Neurol. Published online May 15, 2023. doi:10.1001/jamaneurol.2023.1168

2020: Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors

  • While many reports suggest causality, and often this is a stretch at best, here the authors discuss what is needed to prove a causal relationship and satisfy those requirements.
  • It is a rare example of how you should approach causality, reading the text gives a clear account of the criteria the authors consider to prove causality, and how these are met.
  • 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.
  • Benjamin Mappin-Kasirer, Hongchao Pan, Sarah Lewington, Jennifer Kizza, Richard Gray, Robert Clarke, Richard Peto First published May 5, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009437

2020 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 Parkinson Disease (PD) than those with lower intake. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea.
  • 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.
  • Keywords: dietary nicotine, Parkinson disease, neurodegenerative disease

2016: 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

2007 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.
  • 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.

1996 Does nicotine have beneficial effects in the treatment of certain diseases?

  • Nicotine may have therapeutic uses in the treatment of 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.
  • 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 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against Parkinson's Disease (other diseases mentioned in study)
  • 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.


Psoriasis

2012 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.
  • 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 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.
  • 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.
  • Keywords: Pyoderma gangrenosum — Topical nicotine cream — Treatment

1998 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.
  • 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 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.
  • 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.


Sarcoidosis

2021 Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis

2021 A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis

2013 Nicotine Treatment Improves Toll-Like Receptor 2 and Toll-Like Receptor 9 Responsiveness in Active Pulmonary Sarcoidosis

  • The immune phenotype of patients with symptomatic sarcoidosis treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
  • 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


Seizures / Epilepsy

2021 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 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 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.

2020 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 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.

2012 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.
  • 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

2003 Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study

  • In this individual with refractory ADNFLE, nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
  • 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


Sleep Apnea

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against sleep apnea (other diseases / issues mentioned in study)
  • 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: 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.
  • 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.


Smoking Cessation / Preventing Relapse

Resource Doc: 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

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 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 spinal cord injury (SCI).
  • The results of the present study indicate that 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.
  • 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


Tourette's Syndrome

2012 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.
  • 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 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 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.
  • 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 Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study

  • 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
  • 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 Nicotine for the treatment of Tourette's syndrome

  • Within 24 hr of the application of a single 7-mg 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 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.
  • 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 Does nicotine have beneficial effects in the treatment of certain diseases?

  • nicotine may have therapeutic uses in the treatment of 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.
  • 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 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 transdermal nicotine patch (TNP) for 24 hours. While there was a broad range in individual response, application of the TNP produced significant reductions in 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
  • 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 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 TD, and showed lesser effects on TD when used alone.
  • 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.

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against Tourette's disease (other diseases mentioned in study)
  • 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 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.
  • 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.


Weight Loss / Appetite Control / Metabolism / Obesity

2011 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.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • 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

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in reduction of body weight
  • 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.


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