Nicotine therapeutic benefits: Difference between revisions

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<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>

<big>'''''Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that fewer people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine. Some of these studies show a potential benefit, not proof of a benefit. Some of the studies are animal studies, not human studies.'''''</big>

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

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

* While smoking has been associated with many negative consequences to human health, one possible benefit is that nicotine could improve cognitive functions. Previous studies have suggested that smoking may influence brain-derived neurotrophic factor (BDNF) levels.

* Our research revealed that tobacco product use led to an increase in working memory and human plasma BDNF levels. Furthermore, nicotine was responsible for the elevation in BDNF levels, which showed dose-dependent increases in both serum and the hippocampus, and improved memory performance.

* Animal study (rat)

* ''Yingyan Li, PhD, Xin Li, Yaning Fu, PhD, Wenjun Mou, Zuxin Chen, PhD, Ping Wu, PhD, Fanglin Liu, PhD, Huan Chen, PhD, Hongwei Hou, PhD, Qingyuan Hu, PhD: Nicotine & Tobacco Research'', ntaf060, <nowiki>https://doi.org/10.1093/ntr/ntaf060</nowiki>

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.845646/full Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms]===

*"Our review of evidence supports the finding that individuals with ADHD are at greater vulnerability for both initiation and continuation of smoking (both cigarettes, e-cigarettes)."

*"Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes."

*Taylor, M. R., Carrasco, K., Carrasco, A., & Basu, A. (2022). Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms. Frontiers in Neuroscience, 16, 845646. https://doi.org/10.3389/fnins.2022.845646

*Funds for open access publication fees are contributed by the Faculty of Health, University of Canterbury and University of Canterbury library.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===

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*Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.

*Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.

===2008 [https://pmc.ncbi.nlm.nih.gov/articles/PMC2446482/ Transdermal Nicotine in Adult ADHD With Depression and Anxiety]===

*"This case report neither rules out the placebo effect, nor does it prove that transdermal nicotine is useful in managing adult ADHD with depression and anxiety. However, it does suggest that the beneficial effect of transdermal nicotine may be attributed to biobehavioral pathways common to chronic nicotine withdrawal and ADHD with depression and anxiety. Nicotine agonists and delivery systems may be new treatments for adult ADHD. Larger well-designed studies are warranted to evaluate the therapeutic potential of nicotine delivery systems in otherwise medically stable adults with ADHD accompanied by depression and anxiety. Further exploration of the nicotinic-cholinergic system may also expand our understanding of the neuropsychiatry underlying ADHD."

*Citation: Cocores JA. Transdermal nicotine in adult ADHD with depression and anxiety. Prim Care Companion J Clin Psychiatry. 2008;10(3):253-4. doi: 10.4088/pcc.v10n0312f. PMID: 18615164; PMCID: PMC2446482.

*Dr. Cocores reports no financial affiliations or other relationships relevant to the subject of this letter.

===2007 [https://www.academia.edu/2412620/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===

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*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~~]===

===2007: [https://pubmed.ncbi.nlm.nih.gov/18022679/ Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder]===

*(~~Note~~: ~~Need~~ to ~~add summary)~~

*Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.

**Citation: Potter AS, Newhouse PA. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav. 2008 Feb;88(4):407-17. doi: 10.1016/j.pbb.2007.09.014. Epub 2007 Sep 26. PMID: 18022679.

***Acknowledgement: Paywalled, unable to access.

===2006 [https://www.academia.edu/17983526/The_reinforcing_effects_of_nicotine_and_stimulant_medication_in_the_everyday_lives_of_adult_smokers_with_ADHD_A_preliminary_examination The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination]===

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*[https://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]

*Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.

*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.

*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.

*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention

**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783

***Acknowledgement: None stated

===2003: [https://www.academia.edu/2412608/Is_There_a_Link_Between_Adolescent_Cigarette_Smoking_and_Pharmacotherapy_for_ADHD Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?]===

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*The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.

*Citation: Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull. 1996;32(1):67-73. PMID: 8927677.

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

*Lists references

='''~~Ageing~~'''=

='''Aging'''=

===2023: [https://www.nature.com/articles/s41467-023-36543-8 Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity]===

*Abstract "Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms."

*Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8

**Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8

***Acknowledgement: This work was supported by grants from Shenzhen Science and Technology Program (KQTD20210811090117032), Shenzhen Key Laboratory of Viral Vectors for Biomedicine (ZDSYS20200811142401005), CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024) and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).

='''Allergies / Hayfever / Histamines'''=

='''Akathisia'''=

===1997: [https://pubmed.ncbi.nlm.nih.gov/9399378/ Treatment of neuroleptic-induced akathisia with nicotine patches]===

*We administered 14 mg nicotine patches to 16 patients, all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia.

*[https://sci-hub.se/10.1007/s002130050436 PDF Version]

**Citation: Anfang MK, Pope HG Jr. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl). 1997 Nov;134(2):153-6. doi: 10.1007/s002130050436. PMID: 9399378.

='''Alcohol Use Disorder'''=

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===

*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.

**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.

***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

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

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203434/ Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation]===

*Animal Study

*In this study, the effect of environmental tobacco smoke (ETS) on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated.

*In summary, ETS suppressed allergen-induced nasal responses including NHR by inhibiting allergen-specific Th2 cell responses. Although our present findings do not deny harmful effects of cigarette smoking, nicotine as a component of ETS may be a target to treat Th2-mediated allergic diseases, including allergic rhinitis (AR).

**Citation: Nishimura T, Kaminuma O, Saeki M, Kitamura N, Mori A, Hiroi T. Suppressive effect of environmental tobacco smoke on murine Th2 cell-mediated nasal eosinophilic inflammation. Asia Pac Allergy. 2020 Apr 27;10(2):e18. doi: 10.5415/apallergy.2020.10.e18. PMID: 32411583; PMCID: PMC7203434.

***Acknowledgement: This work was supported in part by funding from the Smoking Research Foundation provided to Osamu Kaminuma.

===2017: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440386/ Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium]===

*Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

*Citation: Skaaby T, Taylor AE, Jacobsen RK, et al. Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Sci Rep. 2017 May 22;7(1):2224. doi: 10.1038/s41598-017-01977-w. PMID: 28533558; PMCID: PMC5440386.

**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).

***Acknowledgement: This work was supported by the Medical Research Council (grant numbers: MR/J01351X/1, MC_UU_12013/6). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

===2014: [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085888 Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model]===

*Animal study

*In this study, nicotine treatment significantly ameliorated FA [Food Allergy], mainly due to the suppression of upregulated mucosal immune responses via α7 nAChRs on immune cells. Therefore, the therapeutic effects of nicotine and GTS-21 on the FA model raise the possibility that a strategy for drug discovery against FA by targeting α7 nAChRs could potentially have therapeutic benefits.

**Citation: Yamamoto T, Kodama T, Lee J, Utsunomiya N, Hayashi S, Sakamoto H, Kuramoto H, Kadowaki M. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS One. 2014 Jan 16;9(1):e85888. doi: 10.1371/journal.pone.0085888. PMID: 24454942; PMCID: PMC3894205.

===~~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]===

===2008: [https://journals.aai.org/jimmunol/article/180/11/7655/84640/Nicotine-Primarily-Suppresses-Lung-Th2-but-Not Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens]===

*Animal Study

*~~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.

*hese results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia, mucous production, and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.

*Citation: 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.~~

**Citation: Neerad C. Mishra, Jules Rir-sima-ah, Raymond J. Langley, Shashi P. Singh, Juan C. Peña-Philippides, Takeshi Koga, Seddigheh Razani-Boroujerdi, Julie Hutt, Matthew Campen, K. Chul Kim, Yohannes Tesfaigzi, Mohan L. Sopori; Nicotine Primarily Suppresses Lung Th2 but Not Goblet Cell and Muscle Cell Responses to Allergens1. J Immunol 1 June 2008; 180 (11): 7655–7663. https://doi.org/10.4049/jimmunol.180.11.7655

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

***Acknowledgement: This work was supported in part by grants from the National Institutes of Health (R01-DA017003, R01-DA04208-15, and R01-DA042087S).

===2004: [https://link.springer.com/article/10.1007/s00011-004-1249-1 The effect of nicotine on basophil histamine release]===

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

*[https://sci-hub.st/10.1007/s00011-004-1249-1 PDF Full Version]

*Citation: Thompson-Cree, M.E.M., Stevenson, M.R., Shields, M.D. et al. The effect of nicotine on basophil histamine release. Inflamm. res. 53, 211–214 (2004). https://doi.org/10.1007/s00011-004-1249-1

**Citation: Thompson-Cree, M.E.M., Stevenson, M.R., Shields, M.D. et al. The effect of nicotine on basophil histamine release. Inflamm. res. 53, 211–214 (2004). https://doi.org/10.1007/s00011-004-1249-1

='''Alzheimer / Dementia / Mild Cognitive Imparement (MCI)'''=

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===

*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.

**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2

***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

===2013 [https://link.springer.com/article/10.1007/s12017-013-8242-1 Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation]===

*Animal Study

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*[https://sci-hub.st/10.1080/13607860220126808 PDF Version]

*Citation: K. N. Murray & N. Abeles (2002) Nicotine's effect on neural and cognitive functioning in an aging population, Aging & Mental Health, 6:2, 129-138, DOI: 10.1080/13607860220126808

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.

*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.

*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.

*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention

**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783.

***Acknowledgement: None stated

===2002 [https://pubmed.ncbi.nlm.nih.gov/12436427/ Nicotinic receptors in aging and dementia]===

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='''~~Aphthous ulcers~~'''=

='''Antimicrobial Agent'''=

*As a follow-up to these provocative findings, future related studies should examine whether nicotine exerts its anti-microbial effects against a much broader range of indigenous microflora than has been studied so far, along with focusing on the molecular biologic mechanisms and host pathologic changes associated with nicotine-mediated killing of the oral and intestinal microflora.

**Citation: Pavia CS, Plummer MM. Clinical implications of nicotine as an antimicrobial agent and immune modulator. Biomed Pharmacother. 2020 Sep;129:110404. doi: 10.1016/j.biopha.2020.110404. Epub 2020 Jun 27. PMID: 32603888; PMCID: PMC7320263.

***Acknowledgement: This work was partially supported by funds provided by the Department of Biomedical Sciences, NYIT College of Osteopathic Medicine. The authors thank the publisher of the Journal of Medical Microbiology (JMM) for granting us permission to reuse in this paper, without being subject to any copyright infringement, some of the material previously published by one of us (CSP) in the JMM. We also thank Jane Pavia for contributing to the design of the graphical abstract.

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

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

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

*The theory that nicotine is known as the protective factor is also supported by three case reports, in which aphthous ulcers were prevented or healed while the patients used nicotine replacement materials.

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

*To summarize, the use of pure nicotine in therapeutic forms, seems to be a proper alternative to treat aphthous ulcers; however, there has not been any evidence-based case-control study to prove such claim.

*Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

**Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

===2014: [https://pubmed.ncbi.nlm.nih.gov/25584320/ Recurrent aphthous ulcers among tobacco users- hospital based study]===

*The tobacco consumers have less frequency of aphthous ulceration compared non users.

**Citation: Mohamed S, Janakiram C. Recurrent aphthous ulcers among tobacco users- hospital based study. J Clin Diagn Res. 2014 Nov;8(11):ZC64-LC66. doi: 10.7860/JCDR/2014/10368.5145. Epub 2014 Nov 20. PMID: 25584320; PMCID: PMC4290331.

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===

*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.

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

*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

**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2004: [https://pubmed.ncbi.nlm.nih.gov/15370162/ The relationship between smoking cessation and mouth ulcers]===

*Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.

**Citation: McRobbie H, Hajek P, Gillison F. The relationship between smoking cessation and mouth ulcers. Nicotine Tob Res. 2004 Aug;6(4):655-9. doi: 10.1080/14622200410001734012. PMID: 15370162.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12108762/ Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine]===

*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.

*[https://sci-hub.st/10.1034/j.1601-0825.2002.01826.x PDF Version]

*Citation: Atkin PA, Xu X, Thornhill MH. Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Dis. 2002 May;8(3):173-6. doi: 10.1034/j.1601-0825.2002.01826.x. PMID: 12108762.

**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.

*[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

===1992: [https://pubmed.ncbi.nlm.nih.gov/1408021/ Smokeless tobacco use prevents aphthous stomatitis]===

*In (contrast to cigarette smoking, however, few components other than nicotine are systemically absorbed by ST users. Thus if the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.

*[https://sci-hub.se/10.1016/0030-4220(92)90296-3 PDF Version]

**Citation: Grady D, Ernster VL, Stillman L, Greenspan J. Smokeless tobacco use prevents aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):463-5. doi: 10.1016/0030-4220(92)90296-3. PMID: 1408021.

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

*The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers.

*[https://sci-hub.st/10.5694/j.1326-5377.1991.tb121180.x PDF Version]

*Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x

**Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x

='''Arthritis/Skeletal'''=

==Osteoarthritis==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2019 [https://journals.aai.org/jimmunol/article/203/2/485/107400/Nicotine-Attenuates-Osteoarthritis-Pain-and-Matrix Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor]===

*In conclusion, stimulation of α7-nAChRs by nicotine attenuates MIA-induced OA pain and cartilage degradation. This protective effect of nicotine can be associated with the inhibition of MMP-9 overexpression through the PI3K/Akt/NF-κB signaling pathway. Although the use of nicotine is limited by its nonspecific effects, this study provides novel evidence supporting the future development of therapeutic strategies for inflammatory diseases via the cholinergic anti-inflammatory pathway.

**Citation: Teng P, Liu Y, Dai Y, Zhang H, Liu WT, Hu J. Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor. J Immunol. 2019 Jul 15;203(2):485-492. doi: 10.4049/jimmunol.1801513. Epub 2019 May 31. PMID: 31152077.

***This work was supported by grants from the National Natural Science Foundation of China (81373397, 81672218, and 81603092) and the Department of Science, Education, and Health Program of Jiangsu Province (QNRC 2016606 and QNRC 2016604).

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

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2016 [https://www.spandidos-publications.com/mmr/14/6/5057 Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration]===

*Animal study

*Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.

**Citation: Li S, Zhou B, Liu B, Zhou Y, Zhang H, Li T, Zuo X. Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration. Mol Med Rep. 2016 Dec;14(6):5057-5064. doi: 10.3892/mmr.2016.5904. Epub 2016 Oct 31. PMID: 27840928; PMCID: PMC5355730.

***Acknowledgement: The present study was supported by a grant from the National Natural Science Foundation of China (grant no. 81571602).

===2014 [https://pubmed.ncbi.nlm.nih.gov/24313917/ Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells]===

*Animal Study

Line 231:

Line 368:

*[https://sci-hub.st/10.3109/14397595.2013.862352 PDF Full paper]

**Citation: Yang Y, Yang Y, Yang J, Xie R, Ren Y, Fan H. Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells. Mod Rheumatol. 2014 Sep;24(5):781-7. doi: 10.3109/14397595.2013.862352. Epub 2013 Dec 9. PMID: 24313917.

***Acknowledgement: This work was supported by The Shanghai Committee of Science and Technology Project, China (Grant No. 12GWZX0201,11140902900).

===2014 [https://www.sciencedirect.com/science/article/abs/pii/S0014299914003033 Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine]===

*Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses, may improve the Th1/Th2 imbalance in CIA, and provide a new justification for its application in the clinical treatment of RA.

*[https://sci-hub.st/10.1016/j.ejphar.2014.04.019 PDF Full paper]

**Citation: Wu S, Luo H, Xiao X, Zhang H, Li T, Zuo X. Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol. 2014 Jul 15;735:97-104. doi: 10.1016/j.ejphar.2014.04.019. Epub 2014 Apr 19. PMID: 24755145.

***Acknowledgement: This work was supported by a grant from the National Natural Science Foundation of China, People's Republic of China [81102261] and the Innovative Research Funds for the Central South University, People's Republic of China. [CX2012B088].

===2009 [https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.24177 Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice]===

Line 237:

Line 380:

*Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction.

**Citation: van Maanen MA, Lebre MC, van der Poll T, LaRosa GJ, Elbaum D, Vervoordeldonk MJ, Tak PP. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 2009 Jan;60(1):114-22. doi: 10.1002/art.24177. PMID: 19116908.

='''Ataxia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===

*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.

**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.

***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

= '''Auditory''' =

===2021 [https://www.nature.com/articles/s41598-021-92588-z Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers]===

*The present study evaluated acute effects of oral nicotine treatment on three auditory tasks in young adult and elderly, healthy, non-smoking individuals. All had normal hearing within the frequency range of the stimuli presented for the three tasks. Compared to pre-treatment performance, nicotine improved frequency discrimination. Compared to placebo, nicotine produced no overall effects on the two frequency related tasks, but significantly improved intensity discrimination, with more improvement obtained for those who had lower baseline performance. The present results support the hypothesis that nicotine enhances auditory processing, but this enhancement is task-dependent.

Line 250:

Line 402:

*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: [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~~] ===~~

===2025: [https://link.springer.com/article/10.1007/s12035-025-04894-6 Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism]===

*Animal Study

*Accumulating evidence indicates that nicotinic receptor subtypes are altered in the brains of autistic individuals, and nicotinic acetylcholine receptors (nAChRs) play essential roles in autistic profiles in BTBR T+ Itpr3tf/J mice.

*Biochemical analysis showed that nicotine had significantly decreased the concentration of inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, and GM-CSF in the serum, and reduced the expression levels of intracellular pro-inflammatory cytokines (IL-17 & IFN-γ) on CD4+ and CD8+ T cells in the blood while mecamylamine reversed the effect of IL-17+ CD4+ T cells.

*Nicotine administration up-regulated the expressions of α7, α4, and β2 nAChRs in the prefrontal cortex in BTBR T+ Itpr3tf/J mice.

*The current results indicate that nAChRs play a significant role, at least in part, in ASD and might serve as a crucial target for therapeutic interventions in ASD.

**Citation: AlSharari, S.D., Mahmood, H.M., Alasmari, A.F. et al. Nicotine Attenuates Molecular Signalings in the BTBR T+ Itpr3tf/J Mouse Model of Autism. Mol Neurobiol (2025). https://doi.org/10.1007/s12035-025-04894-6

***Acknowledgement: Researchers Supporting Project number (RSPD2025R829), King Saud University, Riyadh, Saudi Arabia. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

* 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.

===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]===

* 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.

*Animal Study

* 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.

*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.

* 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.

*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.

* ~~Mouse study, may not explain human response~~

*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.

* Autism ~~Research~~ 2020 Aug;13(8):1311-1334 doi: 10.1002/aur.2342. Epub 2020 Jul 21.

*LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.

*[https://sci-hub.st/10.1002/aur.2342 PDF Full paper]

**Citation: Mahmood HM, Aldhalaan HM, Alshammari TK, Alqasem MA, Alshammari MA, Albekairi NA, AlSharari SD. The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model. Autism Res. 2020 Aug;13(8):1311-1334. doi: 10.1002/aur.2342. Epub 2020 Jul 21. PMID: 32691528.

***Acknowledgement: The authors would like to thank the support from the Center for Autism Research (CFAR), King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia.

===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===

===2018: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===

*Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.

*Our results also suggest that TN may have a beneficial effect on aggression, irritability, and sleep in ASD, though the sample size of this study is too small to make definitive conclusions.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/pdf/nihms-950880.pdf PDF Version]

*Citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7. PMID: 29536216; PMCID: PMC6394231.

**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).

***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~~

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

*Animal Study

*

**Citation:

***Acknowledgement:

===2016: [https://pubmed.ncbi.nlm.nih.gov/27638450/ Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system]===

*Animal Study

*

*[https://sci-hub.st/10.1016/j.neuropharm.2016.09.013 PDF Full paper]

**Citation:

***Acknowledgement:

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

*Animal Study

*

**Citation:

***Acknowledgement:

='''Behcet's disease'''=

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

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

===2010 [https://academic.oup.com/rheumatology/article/49/3/501/1786816 Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series]===

*In this report, we describe five ex-smoker [[Special:MyLanguage/Abbreviations|'''BD''']] patients with active mucocutaneous lesions, not responsive to standard pharmacological treatments and treated with transdermal nicotine patches. Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of all mucocutaneous lesions within 6 months of observation.

*[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~~

===2007 [https://www.jidonline.org/article/S0022-202X(15)33112-2/fulltext Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease]===

*"In conclusion, we observed substantial inhibitory effects of CSE and nicotine on IL-8 and to a lesser extent on IL-6 release by human keratinocytes and HMEC-1 endothelial cells. These findings may explain the beneficial effect of smoking in BD, also because IL-8, and to some extent IL-6, are likely to induce pivotal proinflammatory signals in this disease (Lee et al., 1993). Nicotine may cause immunoregulation by affecting chemokine/cytokine production. This study also demonstrates the different behavior of cells in terms of cytokine release when stimulated with BD patients' sera compared to those of healthy individuals. The in vitro evidence of beneficial effects of nicotine in BD is fundamental to our ongoing clinical trial with nicotine transdermal patches in BD. In addition, the detected beneficial effect of biochanin A implicates this compound as a candidate for future developments in aphthae treatment. The development of topical nicotinic cholinergic receptor subtype-specific agonists is likely to exhibit beneficial effects on skin and mucosae without inducing systemic adverse effects."

**Citation: Kalayciyan A, Orawa H, Fimmel S, Perschel FH, González JB, Fitzner RG, Orfanos CE, Zouboulis CC. Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease. J Invest Dermatol. 2007 Jan;127(1):81-9. doi: 10.1038/sj.jid.5700492. Epub 2006 Sep 28. PMID: 17008886.

***Acknowledgement: Dr Kalayciyan was supported by a grant of the Berlin Foundation for Dermatology. The research project was supported by the Deutsches Register Morbus Adamantiades–Behçet e.V.

===2000 [https://www.nejm.org/doi/10.1056/NEJM200012143432418?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome]===

*We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.

*[https://sci-hub.st/10.1056/NEJM200012143432418 PDF Version] (Note: Need to scroll down to the correct section)

*Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418

**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~~'''=

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

===2025: [https://pubmed.ncbi.nlm.nih.gov/39921606/ The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]===

*Animal Study

*The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke. This finding suggests that targeting the BBB, especially endothelial cells, with nicotine treatment is a promising therapeutic strategy for brain injury after ischemic stroke.

**Citation: Pang Q, Yan X, Chen Z, Yun L, Qian J, Dong Z, Wang M, Deng W, Fu Y, Hai T, Chen Z, Rong X. The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier. Nicotine Tob Res. 2025 Feb 8:ntaf034. doi: 10.1093/ntr/ntaf034. Epub ahead of print. PMID: 39921606.

***Acknowledgement: Paywalled, unable to access

===2024: [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===

*Animal Study

*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.

**Citation: Abbaspour S, Fahanik-Babaei J, Adeli S, Hermann DM, Sardari M. Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state. Exp Neurol. 2024 Sep 13;382:114946. doi: 10.1016/j.expneurol.2024.114946. Epub ahead of print. PMID: 39278587.

***Funding: None

===2024: [https://pubmed.ncbi.nlm.nih.gov/38698493/ Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury]===

*Animal study

*Conclusioin: "Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions."

**Citation: Wang D, Li X, Li W, Duong T, Wang H, Kleschevnikova N, Patel HH, Breen E, Powell S, Wang S, Head BP. Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury. Br J Pharmacol. 2024 Sep;181(17):3082-3097. doi: 10.1111/bph.16395. Epub 2024 May 2. PMID: 38698493.

***Acknowledgement: H. H. P. and B. P. H. hold equity and are non-paid consultants with Eikonoklastes Therapeutics LLC. Funding information: (TRDRP 2020 T31IR1834 to BPH, VA Merit BX003671 and VA RCS BX006318 to BPH, AL210059 to BPH, Craig H. Neilsen Foundation 886964 to SW and BX005229 to HHP).

===2004 [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===

===2004: [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===

*Several studies have shown that nicotine treatment can attenuate cognitive deficits produced by medial septal lesions, lesions of the nucleus basalis, and traumatic brain injury.

*[https://sci-hub.st/10.1196/annals.1332.019 PDF Version]

*Citation: Pauly JR, Charriez CM, Guseva MV, Scheff SW. Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease. Ann N Y Acad Sci. 2004 Dec;1035:316-34. doi: 10.1196/annals.1332.019. PMID: 15681815.

**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.

***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'''=

===2021 [https://www.mdpi.com/1660-3397/19/2/118 α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells]===

*Animal Study

*We tested the effects of nicotine, which is an agonist for all nAChRs with the exception of α9 subtype for which it is antagonist. At concentrations of 0.001–0.1µL/mL (6.1 µM–0.61 mM), nicotine exerted no effect on the proliferative activity of glioma C6 cells and the loss of viability was 1–4% (Figure S2). Analysis by light microscopy showed that nicotine at concentrations of 1 µL/mL (6.1 mM) and higher induced morphological changes like cell rounding up and loss of processes followed by surface detachment (Figure 3). Despite these changes, we investigated the effect of nicotine at a concentration of 1 μL/mL (6.1 mM) on the proliferation and viability of C6 cells. At this nicotine concentration, inhibition of proliferation was observed, which after 72 h led to a decrease in the number of cells by more than two times; the viability was also reduced (Figure S2). However, it should be taken into account that the reason for such a strong decrease in the concentration of cells may be their detachment from the surface and, as a consequence, the cessation of division. We tested acetylcholine at concentrations ranging from 2 µM to 2 mM with incubation times of 24, 48 and 72 h. No effects of acetylcholine were observed.

**Citation: Terpinskaya, T. I., Osipov, A. V., Kryukova, E. V., Kudryavtsev, D. S., Kopylova, N. V., Yanchanka, T. L., Palukoshka, A. F., Gondarenko, E. A., Zhmak, M. N., Tsetlin, V. I., & Utkin, Y. N. (2021). α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Marine Drugs, 19(2), 118. https://doi.org/10.3390/md19020118

***Acknowledgement: This work was supported by the Belarusian Republican Foundation for Fundamental Research, project number M20R-254, and the Russian Foundation for Basic Research, project number 20-54-00033.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S001448272030416X?via%3Dihub Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells]===

*Nicotine inhibits ovarian cancer cell ERK and p38 [[Special:MyLanguage/Abbreviations|'''MAPK''']] signaling.

*Nicotine inhibits ovarian cancer proliferation and spheroid invasion.

*[https://sci-hub.se/10.1016/j.yexcr.2020.112167 PDF Version]

*Citation: Sarah J. Harmych, Jay Kumar, Mesa E. Bouni, Deborah N. Chadee, Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells, Experimental Cell Research, Volume 394, Issue 1, 2020, 112167, ISSN 0014-4827, doi: 10.1016/j.yexcr.2020.112167.

**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.

***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 [https://www.sciencedirect.com/science/article/abs/pii/S0014299913003270?via%3Dihub Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models]===

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*Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the [[Special:MyLanguage/Abbreviations|'''nAChR''']] modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.

*[https://sci-hub.st/https://doi.org/10.1016/j.ejphar.2013.04.022 PDF Version]

*Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.

**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

='''Cannabis / THC'''=

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= '''Cardiovascular''' =

*See also: Brain Injuries and Strokes

~~===2024~~: [https://www.sciencedirect.com/science/article/pii/S0014488624002723 Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state]===

*Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and ~~(2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.~~

=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38529793/ Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects] ===

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* PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.

* Nicotine patches appear to promote blood vessel formation, without adverse effects.

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

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

* The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis.

* The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group.

* The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.

* Animal study (mice)

* Ge Li-Sha, Zhao Jing-Lin, Chen Guang-Yi, Liu Li, Zhou De-Pu & Li Yue-Chun ''Scientific Reports'' volume 5, Article number: 15895 (2015)

='''Chlamydia Pneumoniae'''=

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='''Cognitive / IQ / Memory'''=

*See also: Sleep - REM

=== 2024: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/ An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence] ===

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

* Author: Ahmad Alhowail

===2021: [https://www.sciencedirect.com/science/article/abs/pii/S1001841721007804 Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS]===

*Animal study

*Exposure to nicotine mainly altered the secretion of serotonin, kynurenic acid, choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition, and the change are closely related to the dose and duration of exposure.

**Citation: Chen Z, Fu L, Liu X-A, Yang Z, Li W, Li F, Luo Q. Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS. Chin Chem Lett. 2022;33(6):3101–5.

***Acknowledgement: This work was financially supported by the National Natural Science Foundation of China (No. 22076197), the Scientific Instrument Developing Project of the Chinese Academy of Sciences (No. YJKYYQ20200034), Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development (No. XMHT20190204002), Shenzhen Science and Technology Innovation Commission (No. JCYJ20200109115405930), Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020B1515120080).

*Article: [https://medicalxpress.com/news/2021-10-reveal-nicotine-hippocampal-dependent-cognition.html Researchers reveal how nicotine influences hippocampal-dependent cognition] "These results suggested the acute exposure to nicotine was beneficial to protect the neurons, especially cognitive enhancement, and the elevated picolinic acid continually protected neuronal cognitive function after nicotine withdrawal. Furthermore, the dynamic alterations of neurotransmitter metabolism induced by nicotine might be a possible protective mechanism of nicotine on hippocampal dependent cognition."

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0306452220304723?via%3Dihub Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study]===

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*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/pdf/CN-16-403.pdf PDF Version]

*Citation: Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414. doi: 10.2174/1570159X15666171103152136. PMID: 29110618; PMCID: PMC6018192.

===2017: [https://www.nature.com/articles/npp201715 Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention]===

*Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory–inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.

**Citation: Bueno-Junior, L., Simon, N., Wegener, M. et al. Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Neuropsychopharmacol 42, 1590–1598 (2017). https://doi.org/10.1038/npp.2017.15

***Acknowledgement: This work was supported by São Paulo Research Foundation, Brazil (FAPESP; fellowships 2012/21387-8 and 2012/06123-4) for investigator LSBJ, R01MH084906 (BM), and a pilot fund from the Center for Evaluation of Nicotine in Cigarettes (NWS). The authors declare no conflict of interest.

===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===

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*Citation: Dawkins, L., Turner, J., Hasna, S., & Soar, K. (2012). The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition. Addictive Behaviors, 37(8), 970–973. doi:10.1016/j.addbeh.2012.03.004

*Electronic Cigarette Company (TECC) supplied the e-cigarettes and cartridges for this study. TECC had no involvement in the design or conduct of the study.

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===

*Animal Study

*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).

* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]

**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.

***Acknowledgement: None stated

===2003 [https://www.nature.com/articles/1300202 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects]===

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='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=

*See Also: The Inflamation Section

===2025: [https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00167-8 Long COVID – a critical disruption of cholinergic neurotransmission?]===

*Conclusions: "A review of the literature indicates that a significant disruption of cholinergic neurotransmission might be a central issue for both LC/ME/CFS and PVS. The hypothesis of a viral blockade of nAChRs and the possibility of a competitive reversal of this blockade by LDTN has been corroborated by highly promising results in the broad application of this method to numerous patients. Randomized controlled trials are necessary to determine whether these preliminary results can be substantiated by evidence. However, LDTN application provides many patients with a method that offers a high probability of symptom relief with only minor side effects and represents an affordable therapeutic intervention for the majority of people affected worldwide. Furthermore, dose-finding studies are required to develop individually adapted therapy regimens with regard to dosage and duration of therapy."

*Citation: Leitzke, M., Roach, D.T., Hesse, S. et al. Long COVID – a critical disruption of cholinergic neurotransmission?. Bioelectron Med 11, 5 (2025). https://doi.org/10.1186/s42234-025-00167-8

=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===

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**Citation: Kastratovic N, Markovic V, Arsenijevic A, Volarevic A, Zdravkovic N, Zdravkovic M, Brankovic M, Gmizic T, Harrell CR, Jakovljevic V, Djonov V, Volarevic V. The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis. Nicotine Tob Res. 2024 Aug 5:ntae193. doi: 10.1093/ntr/ntae193. Epub ahead of print. PMID: 39101540.

***Paywalled, unable to view funding/COI

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===

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**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.

*Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.

*[https://sci-hub.st/10.12968/bjon.1996.5.19.1195 PDF Version]

**Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

===1994: [https://pubmed.ncbi.nlm.nih.gov/8114833/ Transdermal nicotine for active ulcerative colitis]===

*The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

**Citation: Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994 Mar 24;330(12):811-5. doi: 10.1056/NEJM199403243301202. PMID: 8114833.

===1991 [https://pubmed.ncbi.nlm.nih.gov/1859921/ Beneficial effects of nicotine]===

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='''Dyskinesia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===

*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.

**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.

***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===

*In summary, our data show that nicotine treatment decreases haloperidol-induced VCMs [vacuous chewing movements] in an established rat model of tardive dyskinesia. The demonstration that nicotine removal leads to a return of VCMs, whereas nicotine re-exposure reduced haloperidol-induced VCMs, suggests a causal relationship. These data have clinical applications for the treatment of tardive dyskinesias associated with long-term antipsychotic treatment using nicotine.

*Bordia T, McIntosh JM, Quik M. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. J Pharmacol Exp Ther. 2012 Mar;340(3):612-9. doi: 10.1124/jpet.111.189100. Epub 2011 Dec 5. PMID: 22144565; PMCID: PMC3286320.

**Citation: Bordia T, McIntosh JM, Quik M. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. J Pharmacol Exp Ther. 2012 Mar;340(3):612-9. doi: 10.1124/jpet.111.189100. Epub 2011 Dec 5. PMID: 22144565; PMCID: PMC3286320.

***Acknowledgement: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS47162, NS59910]; and the National Institutes of Health National Institute of Mental Health [Grant MH53631]

='''Dystonia'''=

===2019: [https://pmc.ncbi.nlm.nih.gov/articles/PMC6379038/ Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders]===

*Accumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.

**Citation: Quik M, Boyd JT, Bordia T, Perez X. Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders. Nicotine Tob Res. 2019 Feb 18;21(3):357-369. doi: 10.1093/ntr/nty063. PMID: 30137517; PMCID: PMC6379038.

***Acknowledgement: This work was supported by grant NS R56NS095965 from the National Institutes of Health.

='''Endurance / Exercise / Athletic Performance'''=

===2024 Article: [https://web.archive.org/web/20241002001111/https://www.golfdigest.com/story/tour-pros-little-helper-does-nicotine-create-a-competitive-advantage Tour Pro’s Little Helper: Does nicotine create a competitive advantage?]===

*"In all, we talked to nearly 100 pro golfers to learn more about the popularity and usage patterns of nicotine on the major professional tours. Some told us they turn to tobacco or nicotine products for an energy boost; others say it helps them concentrate or feel relaxed. But for many, it’s just about keeping on."

===2023 [https://www.mdpi.com/1660-4601/20/2/1009 The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study]===

*The lower perception of pain intensity that we reported after the 8 mg nicotine dose application might be an important factor that affects performance. However, we did not report any improvement in physical performance parameters.

**Citation: Bartík P, Šagát P, Pyšná J, Pyšný L, Suchý J, Trubák Z, Petrů D. The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study. Int J Environ Res Public Health. 2023 Jan 5;20(2):1009. doi: 10.3390/ijerph20021009. PMID: 36673765; PMCID: PMC9859273.

***Acknowledgement: The authors would like to acknowledge the support of Prince Sultan University for paying the article processing charges (APC) of this publication. This study was conducted by the SSDRL research group.

===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745004/ Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players]===

*Our HRV and salivary analysis revealed that nicotine could induce endocrine and sympathetic nerve activity in healthy male baseball players who had never smoked. Compared with the placebo group, the nicotine group exhibited enhanced cognitive function (an average decrease in motor reaction time of 11.14%; an average decrease in motor reaction time of 5.72%) and baseball-hitting performance (an average increase of 34.69%), and small effect sizes were observed for these results. However, muscle strength did not increase after nicotine intake.

**Citation: Fang SH, Lu CC, Lin HW, Kuo KC, Sun CY, Chen YY, Chang WD. Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players. Int J Environ Res Public Health. 2022 Jan 4;19(1):515. doi: 10.3390/ijerph19010515. PMID: 35010774; PMCID: PMC8745004.

***Acknowledgement: Study was supported by the Ministry of Science and Technology in Taiwan (No: MOST 107-2410-H-028-002-MY2 and MOST 109-2410-H-028-009-MY3).

===2022 [https://www.tandfonline.com/doi/full/10.1186/s12970-021-00413-9 Nicotine supplementation enhances simulated game performance of archery athletes]===

*In summary, these results indicated that 2-mg nicotine gum supplementation enhanced cognitive function, decreased saliva α-amylase activity and HRV through stimulating the sympathetic adrenergic system. More importantly, the archery scores were significantly increased after nicotine supplementation.

**Citation: Hung BL, Chen LJ, Chen YY, Ou JB, Fang SH. Nicotine supplementation enhances simulated game performance of archery athletes. J Int Soc Sports Nutr. 2021 Feb 18;18(1):16. doi: 10.1186/s12970-021-00413-9. PMID: 33602279; PMCID: PMC7890628.

***Acknowledgement: Funded by the Taiwan Ministry of Science and Technology (MOST104–2628-H-028-001-MY2).

===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236038/ A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males]===

*The present study has demonstrated that low-dose (2 mg) nicotine gum increases leg extensor torque, but counter-movement jump and anaerobic capacity during WAnT remained unchanged when compared to a placebo, whilst there were minimal effects of the 4-mg nicotine gum on the performance parameters measured. Together with our previous observation [24], these results indicate that nicotine per se can improve exercise endurance and muscular strength, something that WADA should continue to monitor alongside patterns of (mis)use.

**Citation: Mündel T, Machal M, Cochrane DJ, Barnes MJ. A Randomised, Placebo-Controlled, Crossover Study Investigating the Effects of Nicotine Gum on Strength, Power and Anaerobic Performance in Nicotine-Naïve, Active Males. Sports Med Open. 2017 Dec;3(1):5. doi: 10.1186/s40798-016-0074-8. Epub 2017 Jan 13. PMID: 28092056; PMCID: PMC5236038.

***Acknowledgement: This study was funded in part by a grant from the World Anti-Doping Agency.

===2006 [https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2006.033373 Effect of transdermal nicotine administration on exercise endurance in men]===

*Nicotine improved exercise endurance by 17 ± 7%, and in the absence of any effect on the usual peripheral markers, such as ventilation, heart rate and blood metabolites, we conclude that nicotine prolongs endurance by a central mechanism that may involve nicotinic receptor activation and/or altered activity of dopaminergic pathways.

*[https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2006.033373 PDF Version]

*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

**Citation: Mündel T, Jones DA. Effect of transdermal nicotine administration on exercise endurance in men. Exp Physiol. 2006 Jul;91(4):705-13. doi: 10.1113/expphysiol.2006.033373. Epub 2006 Apr 20. PMID: 16627574.

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='''~~HIV/AIDS~~'''=

='''Hashimoto's disease (Hashimoto thyroiditis)'''=

===~~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]===

*[https://www.hopkinsmedicine.org/health/conditions-and-diseases/hashimotos-thyroiditis Hashimoto's Thyroiditis] "is when your thyroid gland becomes irritated or inflamed. Hashimoto thyroiditis is the most common type of this health problem. It may also be called chronic autoimmune thyroiditis. This thyroiditis is an autoimmune disease. It occurs when your body makes antibodies that attack the cells in your thyroid. The thyroid gland becomes overrun with white blood cells and becomes scarred. This makes the gland feel firm and rubbery. The thyroid then can’t make enough of the thyroid hormone."

*~~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~~.

~~ ~~

===2020: [https://www.endocrine-abstracts.org/ea/0070/ea0070oc8.4?_ga=2.114580999.1434360570.1735281186-102848752.1735281184 Cigarette smoking and the risk to develop symptoms of Hashimoto’s thyroiditis]===

*"In patients who had discontinued smoking at the age of 39 years or more, the diagnosis of HT was predominantly made after the discontinuation of smoking."

===2013: [https://onlinelibrary.wiley.com/doi/10.1111/cen.12222 Smoking and thyroid]===

*"Smoking has distinct associations with thyroid function and size in healthy subjects. It has remarkable and contrasting associations with thyroid function in autoimmune thyroid disease (lower risk of Hashimoto's disease and higher risk of Graves’ disease) and with thyroid size in nodular disease (lower risk of thyroid carcinoma and higher risk of nontoxic goitre and multinodularity). The observed associations likely indicate causal relationships in view of consistent associations across studies, the presence of a dose–response relationship and disappearance of the associations after cessation of smoking. Which mechanisms mediate the many effects of smoking remains largely obscure. Probably, they differ between the various effects. The divergent effects of smoking on the expression of autoimmune thyroid disease are intriguing and reminiscent on the contrasting effects of smoking on inflammatory bowel disease: protective against ulcerative colitis (OR 0·41, 0·34–0·48) but risky for Crohn's disease (OR 1·61, 1·27–2·03)."

*[https://sci-hub.st/10.1111/cen.12222 PDF Full paper]

**Citation: Wiersinga, W. M. (2013). Smoking and thyroid. Clinical Endocrinology, 79(2), 145–151. doi:10.1111/cen.12222

***Acknowledgement: None stated

='''HIV (human immunodeficiency virus)'''=

===2025: [https://www.sciencedirect.com/science/article/abs/pii/S0149763425003495 Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential]===

*"Approximately half of people with HIV (PWH) experience neurocognitive impairment (NCI), despite antiretroviral therapies that have turned what was formerly a death sentence to a chronic illness. No targeted treatments exist for HIV-associated NCI, impacting long-term quality of life. Smoking rates in PWH are nearly double those of the general population, and with evidence for pro-cognitive effects of nicotine, this may reflect self-medication. However, clinical studies yield inconsistent findings-some showing benefits, others reporting harm-likely due to variability in nicotine exposure methods, cognitive testing paradigms, withdrawal states, and confounding comorbidities. In contrast, animal studies offer a more controlled framework to isolate the effects of nicotine. Preclinical models suggest that nicotine may mitigate HIV-associated cognitive deficits by acting on α7 nicotinic acetylcholine receptors (nAChRs), leading to reduced neuroinflammation. These findings highlight the therapeutic potential of targeting nAChRs, though mechanisms remain incompletely understood..."

**Citation: Jha NA, Ayoub SM, Brody AL, Young JW. Nicotine and neurocognition in HIV: Translational challenges and therapeutic potential. Neurosci Biobehav Rev. 2025 Aug 23;177:106348. doi: 10.1016/j.neubiorev.2025.106348. Epub ahead of print. PMID: 40854454.

***Acknowledgement: This work was supported by the National Institutes of Health [grant numbers: R01MH134175 (JWY), R01MH128869 (JWY), R01DA051295 (JWY)]...

===2021: [https://pmc.ncbi.nlm.nih.gov/articles/PMC11334575/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===

*However, alternative pathways with more holistic representations of molecular relationships revealed the potential of nicotine as a neuroprotective treatment. It was found that concurrent with nicotine treatment the individual inactivation of several of the intermediary molecules in the holistic pathways caused the downregulation of the HAD pathology molecules. These findings reveal that nicotine may have therapeutic properties for HAD when given alongside specific inhibitory drugs for one or more of the identified intermediary molecules.

**Citation: Krishnan, V., Vigorito, M., Kota, N.K. et al. Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol 17, 487–502 (2022). https://doi.org/10.1007/s11481-021-10027-2

***Acknowledgement: This study was partially supported by National Institute of Health grants DA43448 and DA046258 to SLC.

='''Huntington’s Disease'''=

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*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.

**Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.

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

*[https://www.nhlbi.nih.gov/health/hypersensitivity-pneumonitis Hypersensitivity pneumonitis] is a rare immune system disorder that affects the lungs. This disease is also called bird or pigeon fancier’s lung, farmer’s lung, hot tub lung, cheese worker's lung, Bagassosis, mushroom worker's lung, malt worker's lung, or humidifier lung.

*[https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity pneumonitis] (HP) classified as an interstitial lung disease is characterized by a complex immunological reaction of the lung parenchyma in response to repetitive inhalation of a sensitized allergen.

===2023: [https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity Pneumonitis]===

*Cigarette smoking seems to protect from developing clinically significant HP likely due to nicotine inhibiting macrophage activation and lymphocyte proliferation.

*However, smokers who develop HP have been shown to have a more severe course and higher mortality.

**Citation: Chandra D, Cherian SV. Hypersensitivity Pneumonitis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499918/

===2007: [https://academic.oup.com/qjmed/article-abstract/100/4/233/2258683?redirectedFrom=fulltext Extrinsic allergic alveolitis: incidence and mortality in the general population]===

*We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at ∼0.9 cases per 100 000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39–0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05–4.33).

**Citation: M. Solaymani-Dodaran, J. West, C. Smith, R. Hubbard, Extrinsic allergic alveolitis: incidence and mortality in the general population, QJM: An International Journal of Medicine, Volume 100, Issue 4, April 2007, Pages 233–237, https://doi.org/10.1093/qjmed/hcm008

===2002: [https://www.atsjournals.org/doi/10.1164/rccm.200210-1154OC Inhibitory Effect of Nicotine on Experimental Hypersensitivity Pneumonitis In Vivo and In Vitro]===

*Animal study

*Results of this study show that nicotine reduces the alveolar inflammatory response to S. rectivirgula antigen and affects some AM (stimulated with LPS or S. rectivirgula) functions in vitro. This influence could be, at least in part, responsible for the protection that smokers have against development of HP. Because nicotine is effective in the treatment of ulcerative colitis, it could also be of interest in the treatment of HP and other pulmonary inflammatory diseases.

**Citation: Blanchet MR, Israël-Assayag E, Cormier Y. Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med. 2004 Apr 15;169(8):903-9. doi: 10.1164/rccm.200210-1154OC. Epub 2003 Dec 30. PMID: 14701707.

===1992: [https://pubmed.ncbi.nlm.nih.gov/1344064/ Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum]===

*It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.

**Citation: Arima K, Ando M, Ito K, Sakata T, Yamaguchi T, Araki S, Futatsuka M. Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum. Arch Environ Health. 1992 Jul-Aug;47(4):274-8. doi: 10.1080/00039896.1992.9938361. PMID: 1344064.

===1987: [https://pubmed.ncbi.nlm.nih.gov/3499342/ Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking]===

*Farmer's lung was only slightly more common among atopic than among non-atopic subjects and twice as common among non-smokers as among smokers.

**Citation: Terho EO, Husman K, Vohlonen I. Prevalence and incidence of chronic bronchitis and farmer's lung with respect to age, sex, atopy, and smoking. Eur J Respir Dis Suppl. 1987;152:19-28. PMID: 3499342.

===1977: [https://pmc.ncbi.nlm.nih.gov/articles/PMC470791/ Extrinsic allergic alveolitis: a disease commoner in non-smokers.]===

*In the literature of extrinsic allergic alveolitis non-smokers predominate in those papers in which smoking habits are recorded (Hapke et al., 1968; Schlueter et al., 1969; Schofield et al., 1976). Studies of the prevalence of precipitating antibodies against Micropolyspora faeni in farmers have shown that they are detected significantly more often in non-smokers than in smokers (Morgan et al., 1975).

**Citation: Warren CP. Extrinsic allergic alveolitis: a disease commoner in non-smokers. Thorax. 1977 Oct;32(5):567-9. doi: 10.1136/thx.32.5.567. PMID: 594937; PMCID: PMC470791.

='''Hypothyroidism'''=

===2006: [https://pubmed.ncbi.nlm.nih.gov/16902999/ Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies]===

*Animal Study

*The major finding of the present study is that chronic nicotine treatment reverses hypothyroidism-induced learning, short-term memory, and longterm memory impairment. This is indicated by the ability of chronic nicotine treatment to normalize the performance of hypothyroid rats in the RAWM spatial learning and memory tasks. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of E-LTP and L-LTP, the widely accepted electrophysiological correlates of cognitive function (Bliss and Collingridge, 1993).

* [https://sci-hub.st/10.1002/jnr.21014 PDF Full study]

**Citation: Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci Res. 2006 Oct;84(5):944-53. doi: 10.1002/jnr.21014. PMID: 16902999.

***Acknowledgement: None stated

='''Inflammation'''=

===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871277/ Effect of Nicotine on Immune System Function]===

*Despite the completely destructive and harmful effects of cigarette smoke, nicotine via stimulation of the α7 receptor can promote the anti-inflammatory benefits on the immune system. However, these effects depend on the concentration, and administration methods are different and sometimes contradictory. It can be used successfully to treat or inhibit autoimmune diseases. Although the exact mechanism of this treatment is unknown, it appears to involve inhibiting downstream intracellular pathways that lead to the secretion of pre-inflammatory cytokines.

*Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

**Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

===2023: [https://onlinelibrary.wiley.com/doi/10.1111/acer.15103 Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco]===

*Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD.

**Citation: Bolstad I, Lien L, Moe JS, Pandey S, Toft H, Bramness JG. Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco. Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1352-1363. doi: 10.1111/acer.15103. Epub 2023 May 30. PMID: 37208927.

***Acknowledgement: This work was financially supported by The Research Council of Norway, grant FRIPRO 251140.

===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===

*Analysis of several studies - some animal.

*In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.

*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

*Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889

***Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.

===2021: [https://www.mdpi.com/1660-4601/18/2/483/htm Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study]===

*HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.

*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

*Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

***Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===

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*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.

**Citation: Dratcu L, Boland X. Does Nicotine Prevent Cytokine Storms in COVID-19? Cureus. 2020 Oct 28;12(10):e11220. doi: 10.7759/cureus.11220. PMID: 33269148; PMCID: PMC7704168.

***Acknowledgement: All authors have declared that no financial support was received from any organization for the submitted work.

===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300218/ Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm]===

*Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."

*Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.

**Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.

***Acknowledgement: This work was supported by University of Castilla-La Mancha Research Programme 2020-GRIN-28705.

===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760232/ Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis]===

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* 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.

**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.).

***Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).

*See Also - Related article: [https://mssociety.ca/research-news/article/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of-harmful-immune-cells-into-the-brain-in-mice-with-an-ms-like-disease MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease]

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

*Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila and Chlamydia pneumonia infection...

*Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12

**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]===

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*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.

**Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.

***Acknowledgement: No funding was provided for the preparation of this article.

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

*In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.

*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325452/pdf/0580404.pdf PDF Version]

*Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

**Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===

*Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.

*~~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

*Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129

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

===2011 [https://pubmed.ncbi.nlm.nih.gov/21691078/ Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells]===

*In summary, we showed that nicotine could suppress TNF-α expression mainly through activation of the α7 nAChR subunit, which inhibited the MyD88/IκBα/NFκB signaling pathway in HBE16 airway epithelial cells. These findings may provide new information on the potential pharmacological effects of nicotine and nAChR in the treatment of respiratory inflammatory diseases. Further research on nicotine and nAChRs may provide more evidence for the treatment of inflammatory diseases and the development of related drugs.

*[https://www.karger.com/Article/Pdf/329982 PDF Version]

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

**Citation: Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982

*Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982

***Acknowledgement: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).

===2011 [https://www.sciencedirect.com/science/article/abs/pii/S0306987711001691?via%3Dihub Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis]===

*In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.

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

*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

**Citation: Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

===2008 [https://onlinelibrary.wiley.com/doi/10.1002/jnr.21901 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury]===

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*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

**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.

***Acknowledgement: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.

===2008 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693390/ Neuronal Nicotinic Alpha7 Receptors Modulate Inflammatory Cytokine Production in the Skin Following Ultraviolet Radiation]===

*Animal study

*Cytokine responses to UV in mice administered chronic oral nicotine, a nAChR agonist, were reduced... These results demonstrate that nAChRα7 can participate in modulating a local pro-inflammatory response in the absence of parasympathetic innervation.

**Citation: Osborne-Hereford AV, Rogers SW, Gahring LC. Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation. J Neuroimmunol. 2008 Jan;193(1-2):130-9. doi: 10.1016/j.jneuroim.2007.10.029. PMID: 18077004; PMCID: PMC2693390.

***Acknowledgement: These studies were funded by NIH grants DA015148 and DA018930 (LCG), PO1 HL72903 (LCG, SWR) and the Browning Foundation of Utah.

===2006 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809735/ Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7]===

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*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.

**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.

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*Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.

*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner

===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===

*Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.

*There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.

*People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.

*Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention

**Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783

***Acknowledgement: None stated

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*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 [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]===

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=='''Mental Health - Depression'''==

===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===

*Review includes human and animal studies.

*"Nicotine has been associated with positive effects on cognition and inflammation, which may benefit individuals with neurological and immune system disorders. As a stimulant, nicotine can bind to the acetylcholine receptors on neurons to promote the release of dopamine and alleviate various neurological diseases. Anti-inflammatory effects against some diseases are associated with the cholinergic anti-inflammatory pathway. Nicotine reduces the release of various inflammatory cytokines by binding to the macrophage surface receptors."

*"Nicotine can extensively improve cognition, which has long attracted the interest of researchers. This section introduces the therapeutic effects of nicotine on Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and major depressive disorder (MDD)."

*"Inflammation involves multiple genes and signaling pathways. In addition, it promotes the occurrence and development of various diseases to varying degrees. Nicotine plays an active role in various immune disorders because of its broad anti-inflammatory properties. This section describes the therapeutic effects of nicotine in rheumatoid arthritis (RA), OA, sepsis, endotoxemia, ulcerative colitis (UC), and myocarditis."

**Citation: Cao, Y., Sun, J., Wang, X., Zhang, X., Tian, H., Huang, L., Huang, Z., Zhang, Y., Zhang, J., Li, L., & Zhou, S. (2024). The double-edged nature of nicotine: Toxicities and therapeutic potentials. Frontiers in Pharmacology, 15, 1427314. https://doi.org/10.3389/fphar.2024.1427314

***Acknowledgement: This work was financially supported by the Technology Project of Anhui Zhongyan Industry Co., Ltd. (2022156), Science and Technology Projects of State Tobacco Monopoly Administration (110202201046XX-05), Startup Program of XMU and Fundamental Research Funds for the Central Universities. Authors YC, XW, XZ, HT, YZ, JZ, and SZ were employed China Tobacco Anhui Industrial Co., Ltd.

===2022: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15950 The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study]===

*In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.

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