Nicotine therapeutic benefits

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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.

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

Acne

2010 Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies

  • Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis.
  • Our meta-analysis underlines that there is no evidence to support an association between smoking habits and acne, although in three of the good quality papers a significant protection in the current smoker was found. It necessary to be cautious in declaring that smoking may provide a protective effect in the pathogenesis of acne because the analysis was based on only a small number of studies.

2006 Severe Acne Vulgaris and Tobacco Smoking in Young Men

  • It is crucial to emphasize that any positive effects found must be traced to specific tobacco components that can be therapeutically used without smoking (e.g., nicotine patches or gums), to avoid any “legitimatizing” of smoking based on its beneficial effects on health.
  • Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P=0.0078).
  • Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

1993 Does smoking influence acne?

  • PDF of full study
  • The findings of this study support the hypothesis that some component of cigarette smoke, possibly nicotine, has an anti‐inflammatory action on acne.


ADD / ADHD / Attention

2018 Cognitive Effects of Nicotine: Recent Progress

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

2017: Causal Factors of Increased Smoking in ADHD: A Systematic Review

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

2014: Adult Attention-Deficit/Hyperactivity Disorder and Nicotine Use: A Qualitative Study of Patient Perceptions

  • Participants had different views about the link between cigarette smoking and ADHD. While the majority thought of nicotine as a sort of therapy, viewing smoking as a way to self-medicate symptoms of ADHD, motivations for nicotine use were also related to self-image, desire to belong to a peer-group, and a drive to undermine perceived social norms. Ultimately, these findings can be used by clinicians to improve treatment alliance and collaboration.
  • Alternative Link
  • Citation: Liebrenz, M., Frei, A., Fisher, C. E., Gamma, A., Buadze, A., & Eich, D. (2014). Adult attention-deficit/hyperactivity disorder and nicotine use: a qualitative study of patient perceptions. BMC Psychiatry, 14(1). doi:10.1186/1471-244x-14-141

2011 Cognitive enhancers for the treatment of ADHD

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

2009 Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder

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

2009 A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder

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

2008 Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder

  • Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD.
  • PDF Version
  • Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.
  • Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.

2007 Smoking to self-medicate attentional and emotional dysfunctions

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

2007: Smoking to self-medicate attentional and emotional dysfunctions

  • (Note: Need to add summary)

2006 The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination

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

2006 Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits

  • The results showed nicotine-induced improvement on some measures of sustained attention in the low attention group and some decrement in working memory in the high attention group, which suggests that nicotine tends to optimize rather than improve performance on cognitive tasks.
  • PDF Version
  • Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.

2003: Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?

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

2002 Nicotinic treatment for cognitive dysfunction

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

2001 Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder.

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

1998 Transdermal nicotine effects on attention

  • This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult non-smokers.
  • PDF Version
  • Citation: Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J, Rose JE. Transdermal nicotine effects on attention. Psychopharmacology (Berl). 1998 Nov;140(2):135-41. doi: 10.1007/s002130050750. PMID: 9860103
  • Acknowledgement: The authors thank R.J. Reynolds for financial support of the project. Work on this article was partially supported by Career Science Award (K05MH0122903) to Dr. Conners and Research Scientist Development Award (K02MH00981–02) to Dr. March

1996 Nicotine effects on adults with attention-deficit/hyperactivity disorder

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

1996: Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD)

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


Addiction / Abuse Liability / Dependence (Nicotine)

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

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

2020 Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers

2020 Dependence and Use Characteristics of Adult JUUL Electronic Cigarette Users

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  • Mint-flavored nicotine gum was rated as more palatable than the original nicotine gum, but the improvement in flavor did not increase abuse liability in adults (22 – 50 years old) or young adults (18 –21 years old).
  • PDF Version
  • Citation: Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacol Biochem Behav. 2002 Jun;72(3):559-68. doi: 10.1016/s0091-3057(02)00723-2. PMID: 12175452.
  • Acknowledgement: This study was supported by SmithKline Beecham Consumer Healthcare.


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

2021 Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats

  • Animal Study
  • The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA. (Note: AKA ecstasy)
  • Citation: Kowsari G, Mehrabi S, Soleimani Asl S, Pourhamzeh M, Mousavizadeh K, Mehdizadeh M. Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats. J Chem Neuroanat. 2021 Jun 10;116:101986. doi: 10.1016/j.jchemneu.2021.101986. Epub ahead of print. PMID: 34119664.


Allergies / Hayfever / Histamines

2017: Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium

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

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

  • Animal Study
  • These results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia, mucous production, and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
  • Citation: Mishra NC, Rir-Sima-Ah J, Langley RJ, et al. Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol. 2008 Jun 1;180(11):7655-63. doi: 10.4049/jimmunol.180.11.7655. PMID: 18490768; PMCID: PMC2614131.

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

2004: The effect of nicotine on basophil histamine release

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


Alzheimer / Dementia / Mild Cognitive Imparement (MCI)

2013 Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation

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

2012 Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial

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

2010 Nicotine's effect on neural and cognitive functioning in an aging population

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

2002 Nicotinic receptors in aging and dementia

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

2002 Nicotinic treatment for cognitive dysfunction

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

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

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

1992 Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease

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

1991 Beneficial effects of nicotine

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

1989 The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type

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


Aphthous ulcers

2015 Use of pure nicotine for the treatment of aphthous ulcers

  • The theory that nicotine is known as the protective factor is also supported by three case reports, in which aphthous ulcers were prevented or healed while the patients used nicotine replacement materials.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387635/?report=printablePrintable Version
  • Citation: Motamedi MR, Golestannejad Z. Use of pure nicotine for the treatment of aphthous ulcers. Dent Res J (Isfahan). 2015 Mar-Apr;12(2):197-8. PMID: 25878688; PMCID: PMC4387635.

2011 Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis

  • In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
  • PDF Version
  • Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

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

  • NOTE: Safer Nicotine Wiki does NOT endorse smoking for any potential therapeutic benefits. Smoking has too many severe consequences. Studies showing that less people who smoke end up with a specific ailment are included to show the potential benefits of the nicotine.
  • This study shows that a group of RAS patients is significantly less likely to contain smokers than a matched control population, and among smokers the level of cigarette use was significantly lower in RAS patients than the control population. The perceived negative association between RAS and smoking was supported by this epidemiological study.
  • PDF Version
  • Citation: Atkin PA, Xu X, Thornhill MH. Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Dis. 2002 May;8(3):173-6. doi: 10.1034/j.1601-0825.2002.01826.x. PMID: 12108762.

2000 Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome

  • We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
  • PDF Version (Note: Need to scroll down to the correct section)
  • Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418

1991 Recurrent aphthous ulcers and nicotine

  • The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers.
  • PDF Version
  • Citation: Bittoun, R. (1991), Recurrent aphthous ulcers and nicotine. Medical Journal of Australia, 154: 471-472. https://doi.org/10.5694/j.1326-5377.1991.tb121180.x


Arthritis/Skeletal

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

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

Auditory

2021 Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers

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

2019 Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers

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

Atopic Dermatitis

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

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

Autism

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

  • Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people.
  • Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism.
  • Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model.
  • LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.
  • Mouse study, may not explain human response
  • Autism Research 2020 Aug;13(8):1311-1334 doi: 10.1002/aur.2342. Epub 2020 Jul 21.

2018 An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder

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


Behcet's disease

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

  • In this report, we describe five ex-smoker BD patients with active mucocutaneous lesions, not responsive to standard pharmacological treatments and treated with transdermal nicotine patches. Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of all mucocutaneous lesions within 6 months of observation.
  • PDF Version
  • Citation: Giovanni Ciancio, Matteo Colina, Renato La Corte, Andrea Lo Monaco, Francesco De Leonardis, Francesco Trotta, Marcello Govoni, Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series, Rheumatology, Volume 49, Issue 3, March 2010, Pages 501–504, doi: 10.1093/rheumatology/kep401
  • Keywords: Behçet’s disease, Cigarette smoking, Nicotine therapy, Mucocutaneous lesions

2000 Nicotine Patches for Aphthous Ulcers Due to Behçet's Syndrome

  • We describe a woman with Behçet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. At the age of 35 several large and extremely painful buccal aphthous ulcers developed. Therapy with a nicotine patch led to a regression of all aphthous ulcers within a few days. A month later, after the patient had stopped using the nicotine patches, four aphthous ulcers developed within a week. These ulcers rapidly regressed once she resumed using the nicotine patches.
  • PDF Version (Note: Need to scroll down to the correct section)
  • Citation: Philippe Scheid, M.D., Abraham Bohadana, M.D., Yves Martinet, M.D., Ph.D., Université Henri Poincaré, 54500 Nancy-Vandoeuvre, France, December 14, 2000, N Engl J Med 2000; 343:1816-1817, DOI: 10.1056/NEJM200012143432418


Brain Injury / Disease

2004 Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease

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


Cancer / Cancer Treatments

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

  • Nicotine inhibits ovarian cancer cell ERK and p38 MAPK signaling.
  • Nicotine inhibits ovarian cancer proliferation and spheroid invasion.
  • PDF Version
  • Citation: Sarah J. Harmych, Jay Kumar, Mesa E. Bouni, Deborah N. Chadee, Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells, Experimental Cell Research, Volume 394, Issue 1, 2020, 112167, ISSN 0014-4827, doi: 10.1016/j.yexcr.2020.112167.
  • Acknowledgements: This work was supported by the National Institutes of Health [R15 CA199164] and [R15 CA241898] to D.N.C.
  • Keywords: Nicotine, Ovarian cancer, Spheroid, MAPK, Invasion

2013 Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models

  • Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
  • Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
  • Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the nAChR modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
  • PDF Version
  • Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
  • Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.
  • Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy


Cannabis / THC

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

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

Cardiovascular

2024: Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects

  • This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers.
  • PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
  • Nicotine patches appear to promote blood vessel formation, without adverse effects.

Chlamydia Pneumoniae

  • Chlamydia pneumoniae is a type of bacteria that can cause respiratory tract infections, such as pneumonia. C. pneumoniae is one cause of community-acquired pneumonia or lung infections developed outside of a healthcare setting. However, not everyone exposed to C. pneumoniae will develop pneumonia. Source: US CDC

2013 Targeting the “Cytokine Storm” for Therapeutic Benefit

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


Cognitive / IQ / Memory

2024: 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

  • Whilst it is known that smoking is a leading avoidable cause of diseases including cardiovascular disease, lung disease and cancer, smoking prevalence in the majority of countries remains at 10–40% [1]. Despite the aforementioned health consequences being widely documented and smoking cessation medications having been available for several decades [2], smoking cessation rates remain generally low; in the US for example, based on data from 2018, successful rates were around 7.5% per year
  • A significant improvement in sustained attention task performance was observed following use of both the nicotine containing e-cigarettes and combustible cigarette compared to no product use. Additionally, there were no significant differences between the nicotine containing products, indicating that nicotine use enhanced sustained attention regardless of delivery format. Nicotine containing e-cigarette and combustible cigarette use also significantly improved overall mood of participants compared to no product use, with no significant differences observed between the nicotine containing products. Nicotine containing e-cigarette and combustible cigarette use significantly reduced smoking urges compared to no product use, though combustible cigarette use elicited the greatest reduction in smoking urges.
  • Conclusion
    • Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.
  • The study was an exploratory, randomised, partially-blinded, single-centre, five-arm crossover trial. It was registered prospectively on ISRCTN (ISRCTN35376793) and received ethical approval from the Wales Research Ethics Committee 1 (Cardiff, UK; reference 21/WA/0095). The research was performed in accordance with the Declaration of Helsinki (2013), Good Clinical Practice and applicable regulatory requirements.
  • Harry J. Green, Olivia K. O’Shea, Jack Cotter, Helen L. Philpott, and Nik Newland. Harm Reduct J. 2024; 21: 78. Published online 2024 Apr 6. doi: 10.1186/s12954-024-00993-0 PMCID: PMC10998423
  • Supplementary material:

2023: Editorial: Nicotine and its derivatives in disorders of cognition: a challenging new topic of study

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

2023: Nicotine's effect on cognition, a friend or foe?

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

2021: Molecular insights into the benefits of nicotine on memory and cognition

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

2020 Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study

  • Nicotine improves sustained attention and reduces distractor interference, promoting cognitive stability. Nicotine enhances response times without differential impact on task switching or distraction.
  • PDF Version
  • Citation: Stefan Ahrens, Christiane M. Thiel, Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study, Neuroscience, Volume 444, 2020, Pages 43-53, ISSN 0306-4522, doi: 10.1016/j.neuroscience.2020.07.029.
  • Acknowledgements: This work was supported by a grant from the German Research Foundation DFG TH766/8-1.
  • Key words: nicotine, cholinergic, cognitive control, distraction, task switching, neuroimaging

2019: Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

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

2018 Cognitive Effects of Nicotine: Recent Progress

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

2016: Re-thinking nicotine and its effects

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

2013: A fresh look at tobacco harm reduction: the case for the electronic cigarette

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

2012: The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition

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

2003 Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

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

1996 Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers

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

1994 Smoking and raven IQ

  • Nicotine has recently been shown to enhance measures of information processing speed including the decision time (DT) component of simple and choice reaction time and the string length measure of evoked potential waveform complexity. Both (DT and string length) have been previously demonstrated to correlate with performance on standard intelligence tests (IQ).
  • In this experiment we used the Raven Advanced Progressive Matrices (APM) test. APM scores were significantly higher in the smoking session compared to the non-smoking session, suggesting that nicotine acts to enhance physiological processes underlying performance on intellectual tasks.
  • PDF Version
  • Citation: Stough, C., Mangan, G., Bates, T. et al. Smoking and raven IQ. Psychopharmacology 116, 382–384 (1994). doi: 10.1007/BF02245346
  • Key words: Intelligence, APM, Nicotine, Smoking Cholinergic system

1992 Nicotine as a cognitive enhancer

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


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

2023: The controversial effect of smoking and nicotine in SARS-CoV-2 infection.

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

2023: Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?

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

2023: Treatment of 95 post-Covid patients with SSRIs

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

2020 Does Nicotine Prevent Cytokine Storms in COVID-19?

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

2020 Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm

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

2020: Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system

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

2019: Mitochondria as a possible target for nicotine action

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

Digestive Tract / Bowel

2022 Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects

  • Analysis of several studies - some animal.
  • In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
  • Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.
  • Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889

2011 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

  • Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129

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

  • Smoking has a detrimental effect in Crohn's disease (CD), but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits ulcerative colitis (UC), and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis.
  • In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.
  • PDF Version
  • Citation: J. R. Ingram, J. Rhodes, B. K. Evans, and G. A. O. Thomas, Hindawi Publishing Corporation, Gastroenterology Research and Practice, Volume 2008, Article ID 237185, 6 pages, doi:10.1155/2008/237185
  • Acknowledgements: J. R. Ingram was supported by the Gastrointestinal Foundation Trust. SLA Pharma gave financial support to the project. The authors are indebted to Dr. J. T. Green (of Cardiff and Vale Hospitals Trust) who referred patients, and to Professor G. T. Williams (GTW) who performed all histological assessments.

2004 Transdermal nicotine for induction of remission in ulcerative colitis

  • Ulcerative colitis is largely a disease of nonsmokers and patients who have quit smoking. Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis.
  • PDF Version
  • Acknowledgements: Funding for the IBD/FBD Review Group (October 1, 2005 - September 30, 2010) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch; the Canadian Agency for Drugs and Technologies in Health (CADTH); and the CIHR Institutes of Health Services and Policy Research; Musculoskeletal Health and Arthritis; Gender and Health; Human Development, Child and Youth Health; Nutrition, Metabolism and Diabetes; and Infection and Immunity. Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

1999 Nicotine treatment for ulcerative colitis

  • No withdrawal symptoms suggesting nicotine addiction have been reported either after 4–6 weeks of therapy in short-term studies, or after a period of up to 6 months in the only long-term study available
  • It can be concluded from these data that transdermal nicotine alone has limited efficacy in active ulcerative colitis and is ineffective as maintenance treatment. On the other hand, if administered in combination with mesalazine, nicotine is superior to placebo in promoting clinical remission of ulcerative colitis of mild to moderate degree, may represent an efficacious alternative to steroids in selected cases and, when effective, seems to exert a longer-lasting therapeutic effect than prednisone.
  • PDF Version
  • Citation: Guslandi M. Nicotine treatment for ulcerative colitis. Br J Clin Pharmacol. 1999 Oct;48(4):481-4. doi: 10.1046/j.1365-2125.1999.00039.x. PMID: 10583016; PMCID: PMC2014383.
  • Keywords: enemas, nicotine, transdermal patches, ulcerative colitis

1996 The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.

  • Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial deterrent of UC and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.
  • PDF Version
  • Citation: Birtwistle J. The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis. Postgrad Med J. 1996 Dec;72(854):714-8. doi: 10.1136/pgmj.72.854.714. PMID: 9015463; PMCID: PMC2398677.

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

  • Nicotine may have therapeutic uses in the treatment of ulcerative colitis.
  • Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
  • PDF Version
  • Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against ulcerative colitis (other diseases mentioned in study)
  • PDF Version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.


Down's Syndrome

2001: Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome

  • To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5–31 years) received placebo and a single dose of transdermal nicotine (5mg patch) over 2h in a single-blind, within-subjects repeated measures design.
  • Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.
  • Citation: Bernert G., Sustrova M., Sovcikova E., Seidl R., Lubec G. (2001) Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. In: Lubec G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_19

2000 Effects of transdermal nicotine on cognitive performance in Down's syndrome

  • We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalizable because of small numbers.
  • PDF Version
  • Seidl R, Tiefenthaler M, Hauser E, Lubec G. Effects of transdermal nicotine on cognitive performance in Down's syndrome. Lancet. 2000 Oct 21;356(9239):1409-10. doi: 10.1016/S0140-6736(00)02848-8. PMID: 11052587.
  • Acknowledgements: We thank Pharmacia-Upjohn, Uppsala, Sweden, for providing transdermal nicotine patches. This study was supported by the Red Bull Company, Salzburg.


Endurance / Exercise / Athletic Performance

2006 Effect of transdermal nicotine administration on exercise endurance in men

  • Nicotine improved exercise endurance by 17 ± 7%, and in the absence of any effect on the usual peripheral markers, such as ventilation, heart rate and blood metabolites, we conclude that nicotine prolongs endurance by a central mechanism that may involve nicotinic receptor activation and/or altered activity of dopaminergic pathways.
  • PDF Version
  • Mündel, T. and Jones, D.A. (2006), Effect of transdermal nicotine administration on exercise endurance in men. Experimental Physiology, 91: 705-713. doi: 10.1113/expphysiol.2006.033373


HIV/AIDS

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

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


Huntington’s Disease

2005: Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats

  • These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.
  • In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.
  • PDF Version
  • Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.


Inflammation

2023: Effect of Nicotine on Immune System Function

  • Despite the completely destructive and harmful effects of cigarette smoke, nicotine via stimulation of the α7 receptor can promote the anti-inflammatory benefits on the immune system. However, these effects depend on the concentration, and administration methods are different and sometimes contradictory. It can be used successfully to treat or inhibit autoimmune diseases. Although the exact mechanism of this treatment is unknown, it appears to involve inhibiting downstream intracellular pathways that lead to the secretion of pre-inflammatory cytokines.
  • Citation: Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull. 2023 Jan;13(1):69-78. doi: 10.34172/apb.2023.008. Epub 2022 Jan 4. PMID: 36721811; PMCID: PMC9871277.

2022 Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects

  • Analysis of several studies - some animal.
  • In general, nicotine is beneficial in ulcerative colitis; in particular, nicotine transdermal patches or nicotine enemas have shown significantly improved histological and global clinical scores of colitis, inhibited pro-inflammatory cytokines in macrophages, and induced protective autophagy to maintain intestinal barrier integrity.
  • Acknowledgements: This work was supported by the National Natural Science Foundation of China (grant number 81903319), Natural Science Foundation of Guangdong Province of China (grant number 2021A1515011220), Administration of Traditional Chinese Medicine of Guangdong Province of China (grant number 20211008), Special Fund for Young Core Scientists of Agriculture Science (grant number R2019YJ-QG001), Special Fund for Scientific Innovation Strategy—Construction of High-Level Academy of Agriculture Science (grant number R2018YJ-YB3002), Top Young Talents of Guangdong Hundreds of Millions of Projects of China (grant number 87316004), the foundation of director of Crops Research Institute, Guangdong Academy of Agricultural Sciences (grant number 202205) and Outstanding Young Scholar of Double Hundred Talents of Jinan University of China.
  • Citation: Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X and Zhang W (2022) Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 13:826889. doi: 10.3389/fimmu.2022.826889

2021: Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study

  • HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
  • Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).
  • Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

2020 Does Nicotine Prevent Cytokine Storms in COVID-19?

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

2020 Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm

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

2016 Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis

  • Animal Study
  • This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of EAE mice via multiple nAChRs, including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
  • PDF Version
  • Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
  • Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
  • See Also - Related article: MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease

2013 Targeting the “Cytokine Storm” for Therapeutic Benefit

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

2013 Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis

  • Animal Study
  • Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in EAE as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for MS therapy.
  • PDF Version
  • Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.

2012 Can nicotine use alleviate symptoms of psoriasis?

  • In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
  • PDF Version
  • Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.

2011 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

  • Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129

2011 Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells

  • In summary, we showed that nicotine could suppress TNF-α expression mainly through activation of the α7 nAChR subunit, which inhibited the MyD88/IκBα/NFκB signaling pathway in HBE16 airway epithelial cells. These findings may provide new information on the potential pharmacological effects of nicotine and nAChR in the treatment of respiratory inflammatory diseases. Further research on nicotine and nAChRs may provide more evidence for the treatment of inflammatory diseases and the development of related drugs.
  • PDF Version
  • Funding: This work was supported by the National Natural Science Foundation of China (No.81070031), and China-Russia Cooperation Research Program (81011120108).
  • Li, Q., Zhou, X. D., Kolosov, V. P., & Perelman, J. M. (2011). Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(5), 605–612. https://doi.org/10.1159/000329982

2011 Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis

  • In addition, nicotine or its metabolites can result in decrease of pro-inflammatory cytokines like tumor necrosis factor-α, interleukins 1 and 6, and increase of anti-inflammatory cytokine interleukin-10. Consequently, there is reduced susceptibility to RAS due to immunosuppression and/or reduction in inflammatory response.
  • PDF Version
  • Subramanyam, R. V. (2011). Occurrence of recurrent aphthous stomatitis only on lining mucosa and its relationship to smoking – A possible hypothesis. Medical Hypotheses, 77(2), 185–187. doi:10.1016/j.mehy.2011.04.006

2008 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury

  • Animal Study
  • Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in spinal cord injury (SCI).
  • The results of the present study indicate that iNOS is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
  • PDF Version
  • Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
  • Acknowledgements: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.

2006 Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-κB phosphorylation and nuclear factor-κB transcriptional activity through nicotinic acetylcholine receptor α7

  • Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-α, prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-1α and MIP-1α, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet’s disease and Crohn’s disease. In addition, the nicotinic acetylcholine receptor-α7 (α7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the α7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes.
  • These suppressive effects of nicotine were caused at the transcriptional level and were mediated through α7nAChR. Nicotine suppressed the phosphorylation of I-κB, and then inhibited the transcriptional activity of nuclear factor-κB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.
  • This supports the therapeutic use of nicotine in some inflammatory diseases; the NF-κB activation pathway is one of the most critical molecular targets of nicotine therapy.
  • Citation: Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. 2006 Oct;146(1):116-23. doi: 10.1111/j.1365-2249.2006.03169.x. PMID: 16968406; PMCID: PMC1809735.


Legionella Pneumophila (Legionnaires' disease)

2013 Targeting the “Cytokine Storm” for Therapeutic Benefit

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


Mental Health

  • See subcategories below


Mental Health - Anxiety

2016: Re-thinking nicotine and its effects

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


Mental Health - Behavior Issues

  • See Also: ADD/ADHD above

2020 Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies

  • Human and Animal Studies
  • Clinical trials and case series report anti-aggressive effects of nicotine. Here we argue that the nAChR system, the molecular basis for the global public health problem of tobacco smoking, may also be a key target for modulation of aggressive behaviors. Future research should aim to clarify which forms of aggression are most strongly affected by nAChR modulation, identify the nAChR subtypes, circuits, and neurobiological mechanisms of nicotine action, and determine whether more selective nAChR-active agents can replicate or improve the serenic effects of nicotine, especially with chronic dosing. Given the prevalence of aggressive behaviors across neuropsychiatric disorders affecting the very young to the very old, these studies have the potential to have a significant impact on public health.
  • PDF Version
  • Citation: Alan S. Lewis, Marina R. Picciotto, Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies, Neuropharmacology, Volume 167, 2020, 107929, ISSN 0028-3908, doi: 10.1016/j.neuropharm.2019.107929.
  • Acknowledgements: This work was supported by National Institutes of Health grants MH116339 (A.S.L.), MH077681 and DA14241 (M.R.P.).
  • Keywords: Nicotine, Nicotinic receptor, Aggression, Aggressive behavior, Impulsivity, Acetylcholine

2018 An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder

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


Mental Health - Depression

2022: The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study

  • In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.
  • Citation: Yebo Yu, Fan Yang, Mingqi Fu, Farooq Ahmed, Muhammad Shahid, Jing Guo, Relationship Between Work-Family Conflict and Depressive Symptoms Among Male Firefighters in China, Journal of Occupational & Environmental Medicine, 10.1097/JOM.0000000000002759, 65, 4, (337-343), (2022).

2021 Adolescent depression symptoms and e-cigarette progression

  • Depression symptoms predicted more rapid e-cigarette progression in adolescents.
  • E-cigarette use was not associated with an escalation in depression symptoms.
  • E-cigarette use was not related to the development of depression symptoms over time.
  • Must pay to view PDF
  • Citation: Afaf F. Moustafa, Shannon Testa, Daniel Rodriguez, Stephen Pianin, Janet Audrain-McGovern, Adolescent depression symptoms and e-cigarette progression, Drug and Alcohol Dependence, Volume 228, 2021, 109072, ISSN 0376-8716, doi.org/10.1016/j.drugalcdep.2021.109072.

2016: Re-thinking nicotine and its effects

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

2000 The Effects of Nicotine on Neural Pathways Implicated in Depression: A Factor in Nicotine Addiction?

  • It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine.
  • PDF Version
  • Citation: Balfour, D. J. ., & Ridley, D. L. (2000). The Effects of Nicotine on Neural Pathways Implicated in Depression. Pharmacology Biochemistry and Behavior, 66(1), 79–85. doi:10.1016/s0091-3057(00)00205-7

2018 Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression

  • Nicotine improves cognitive performance in clinical and preclinical studies.
  • Nicotine may also benefit depressive symptoms and depressive behavior.
  • Cognitive and mood benefits may be mediated by nicotinic effect on neural networks.
  • Nicotine’s effects on networks may reverse network changes seen in depression.
  • Improvement to mood and cognition may particularly benefit older depressed adults.
  • Both preclinical and clinical studies support that nicotine and other nAChR agonists can improve depressive behavior, mood, and cognitive performance. nAChR agonists also demonstrate neuropharmacologic effects that oppose the intrinsic network alterations reported in MDD. Through modulation of intrinsic functional networks, nAChR agonists may reduce depressive symptoms, enhance emotional regulation ability, and improve cognitive deficits common in LLD. For these reasons, we propose nAChR agonists as a potential novel treatment for the mood and cognitive symptoms of LLD.
  • PDF Version
  • Citation: Gandelman, J. A., Newhouse, P., & Taylor, W. D. (2018). Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression. Neuroscience & Biobehavioral Reviews, 84, 289–298. doi:10.1016/j.neubiorev.2017.08.0
  • Acknowledgement: Supported by NIH grants K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences.

2018 Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder

  • In MDD, acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD.
  • PDF Version
  • Citation: Janes AC, Zegel M, Ohashi K, Betts J, Molokotos E, Olson D, Moran L, Pizzagalli DA. Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. Neuropsychopharmacology. 2018 Nov;43(12):2445-2451. doi: 10.1038/s41386-018-0069-x. Epub 2018 Apr 19. PMID: 29795403; PMCID: PMC6180119.
  • Acknoledgements: This project was supported by the National Institute on Drug Abuse grants K10 DA029645 and K02 DA042987 (ACJ). DAP was partially supported by National Institute of Mental Health grant R37 MH068376. Over the past 3 years, DAP has received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Pfizer and Posit Science, for activities unrelated to the current research.

2018 Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Non-Smokers with Late-Life Depression

  • Late Life Depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. Late life depression has no currently approved treatment that improves both its mood and cognitive symptoms.
  • We observed robust response (86.7%) and remission rates (53.3%). There was a significant decrease in MADRS (Montgomery-Asberg Depression Rating scale) over the study, with improvement seen as early as three weeks. We also observed improvement in apathy and rumination. We did not observe improvement on the CPT (Conners Continuous Performance Test), but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing.
  • PDF Version
  • Citation: Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137. PMID: 30192444; PMCID: PMC6129985.
  • Acknowledgements: This research was supported by NIH grant K24 MH110598 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. The sponsor provided funding for the study but did not influence the design or conduct of the study.

2006 Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial

  • These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
  • PDF Version
  • Citation: McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2006 Nov;189(1):125-33. doi: 10.1007/s00213-006-0516-y. Epub 2006 Sep 15. PMID: 16977477.
  • Acknowledgement: This research was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Dr. Rose is an inventor named on several nicotine patch patents and receives royalties from sales of certain nicotine patches.

2002 Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients

  • Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration.
  • Citation: Salin-Pascual RJ. Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Rev Invest Clin. 2002 Jan-Feb;54(1):36-40. PMID: 11995405.

1999 Antidepressant effects of nicotine in an animal model of depression

  • Animal Study
  • Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals.
  • The data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders
  • PDF Version
  • Citation: Tizabi, Y., Overstreet, D., Rezvani, A. et al. Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142, 193–199 (1999). https://doi.org/10.1007/s002130050879
  • Acknowledgements This work was supported in part by the Department of Pharmacology, Howard University, VAMC and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
  • Keywords: Key words Nicotine · Nicotinic receptor · FSL and FRL rats · Animal model of depression

1998 A novel effect of nicotine on mood and sleep in major depression

  • Transdermal nicotine patches increased REM sleep in normal volunteers and depressed patients during 4 days of continuous administration. In addition, a significant improvement of mood was observed in depressed patients. Nicotinic mechanisms may be involved in depression. These findings suggest that nicotine receptor activation may be important in major depression and shows for the first time that nicotine patches may be useful in the treatment of depression.
  • PDF Version
  • Salín-Pascual RJ, Drucker-Colín R. A novel effect of nicotine on mood and sleep in major depression. Neuroreport. 1998 Jan 5;9(1):57-60. doi: 10.1097/00001756-199801050-00012. PMID: 9592048.
  • ACKNOWLEDGEMENT: This work has been supported by the following grants: DGAPA-UNAM IN -200895 to R.J.S-P.

1996 Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression

  • A high frequency of cigarette smoking has been reported among individuals with major depression.
  • Results of the visual analog scale and HAM-D showed a significant improvement in depression after the second day of nicotine patches.
  • Citation: Salín-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL, Delgado-Parra V. Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry. 1996 Sep;57(9):387-9. PMID: 9746444.

1996 Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.

1995 Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients

  • The main finding of the present study was that nicotine patches induced an increase in REM sleep time in depressed patients without any other changes in sleep variables
  • PDF Version
  • Citation: Salín-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colín R. Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology (Berl). 1995 Oct;121(4):476-9. doi: 10.1007/BF02246496. PMID: 8619011.
  • Acknowledgement: This work has been supported in part by FIIRESIN, Fideicomiso-UNAM (to RD-C) and DGAPA-UNAM1N203393 (to RJS-P).

1993 Nicotine Dependence and Major Depression

  • There is, then, no evidence in these data that the occurrence of MDD in persons with a prior history of nicotine dependence might have been caused directly by recent persistent smoking.
  • PDF Version
  • Citation: Breslau N, Kilbey MM, Andreski P. Nicotine Dependence and Major Depression: New Evidence From a Prospective Investigation. Arch Gen Psychiatry. 1993;50(1):31–35. doi:10.1001/archpsyc.1993.01820130033006

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement (mood normalization) (other issues and diseases mentioned in study)
  • PDF version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.


Mental Health - Mental Illness

2022 E-Cigarette Provision to Promote Switching in Cigarette Smokers With Serious Mental Illness—A Randomized Trial

  • This was the first prospective study to compare e-cigarette provision with assessments only to evaluate the appeal and impact of e-cigarettes on smoking behavior, carbon monoxide exposure, and nicotine dependence among smokers with Severe Mental Illness (SMI) who had tried but were unable to quit and were not currently interested in cessation treatment. The finding that e-cigarette provision led to significant reductions in smoking and carbon monoxide without increasing nicotine dependence has implications for reducing harm not only among the millions of smokers with SMI who struggle to quit, but also for other vulnerable smokers who cannot achieve cessation.


Mental Health - OCD (Obsessive Compulsive Disorder)

2020 Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review

  • Nicotine may ameliorate OC symptoms in severe, treatment-refractory OCD patients. Although encouraging, these initial positive effects should be tested in large controlled studies.
  • PDF Version
  • Citation: Piacentino D, Maraone A, Roselli V, Berardelli I, Biondi M, Kotzalidis GD, Pasquini M. Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review. Ann Gen Psychiatry. 2020 Sep 30;19:57. doi: 10.1186/s12991-020-00309-z. PMID: 33014119; PMCID: PMC7528475.


Mental Health - PTSD (Post Traumatic Stress Disorder)

2012 Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study

  • Smokers with PTSD report greater NA (Negative Affects) immediately prior to smoking and greater decreases in NA following smoking, and these findings are consistent with the observed patterns of brain activation in the current study. Thus, our findings provide a neurobiological basis that helps explain why individuals with PTSD are at greater risk of smoking and also experience greater difficulty quitting. The present study is not without its limitations. Our sample size was small and was predominately represented by female smokers.
  • PDF Version
  • Citation: Froeliger, B., Crowell Beckham, J., Feldman Dennis, M., Victoria Kozink, R., & Joseph McClernon, F. (2012). Effects of Nicotine on Emotional Reactivity in PTSD and Non-PTSD Smokers: Results of a Pilot fMRI Study. Advances in Pharmacological Sciences, 2012, 1–6. doi:10.1155/2012/265724
  • Acknowledgement: Department of Veterans Affairs or the National Institutes of Health.


Mental Health - Schizophrenia

2022 Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence

  • Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
  • Twitter thread about this study
  • Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).
  • Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055

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

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

2020 The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review

  • Cognitive and early sensory alterations are core features of schizophrenia. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.
  • PDF Version
  • Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.
  • Keywords: Schizophrenia, Nicotine, Cognition, Early sensory

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

  • Ultimately the authors of the study, published in the journal Nature Medicine, envision their work could lead to new non-addictive, nicotine-based treatments for some of the 51 million people worldwide who suffer from the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.
  • “Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
  • Note: Mouse study; using a model known to mimic human disease.
  • Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
  • Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)

2016: Re-thinking nicotine and its effects

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

2009 Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications

  • The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.
  • PDF Version
  • Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

2002 Nicotinic treatment for cognitive dysfunction

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


Movement Disorders (not diagnosis specific)

2014 Role for the nicotinic cholinergic system in movement disorders; therapeutic implications

  • Animal Study
  • Several nAChR subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.
  • PDF Version
  • Citation: Quik M, Zhang D, Perez XA, Bordia T. Role for the nicotinic cholinergic system in movement disorders; therapeutic implications. Pharmacol Ther. 2014 Oct;144(1):50-9. doi: 10.1016/j.pharmthera.2014.05.004. Epub 2014 May 14. PMID: 24836728; PMCID: PMC4149916.
  • Acknowledgements: This work was supported by grants NS59910 and NS 65851 from the National Institutes of Health.


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

2023: Oral Tobacco Use Linked to Slower MS Progression

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

2016 Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis

  • Animal Study
  • This study provides evidence that nicotine alters the infiltration of proinflammatory monocytes and neutrophils into the CNS of EAE mice via multiple nAChRs, including the α7 and α9 subtypes. Nicotine appears to achieve these effects by inhibiting the expression of CCL2 and CXCL2, two cytokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively. The use of ligands that are selective for one or both of these nAChR subtypes may offer a beneficial clinical outcome, and thus provide a valuable therapeutic strategy for neuroinflammatory disorders such as MS.
  • PDF Version
  • Citation: Jiang W, St-Pierre S, Roy P, Morley BJ, Hao J, Simard AR. Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. J Immunol. 2016 Mar 1;196(5):2095-108. doi: 10.4049/jimmunol.1501613. Epub 2016 Jan 25. PMID: 26810225; PMCID: PMC4760232.
  • Acknowledgements: This work was supported by grants from the Multiple Sclerosis Society of Canada (to A.R.S.), the New Brunswick Health Research Foundation (to A.R.S.), the New Brunswick Innovation Foundation (to A.R.S.), the Nebraska Tobacco Settlement Biomedical Research Fund (to B.J.M.), and the National Institutes of Health (Grant R01DC006907 to B.J.M.). Salary support was provided by the Centre de Formation Médicale du Nouveau-Brunswick (to W.J.) and the New Brunswick Innovation Foundation (to S.S-P. and P.R.).
  • See Also - Related article: MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease

2014 The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

  • Animal Study
  • Our results show that nicotine reduces the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE.
  • PDF Version
  • Citation: Gao Z, Nissen JC, Ji K, Tsirka SE. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One. 2014 Sep 24;9(9):e107979. doi: 10.1371/journal.pone.0107979. PMID: 25250777; PMCID: PMC4176721.
  • Acknowledgements: This work was supported by National Multiple Sclerosis Society awards CA1044A1 and PP181, National Aeronautics and Space Administration NNA14AB04A and National Institutes of Health R01NS42168 (ST), and National Institutes of Health K12GM102778 to JN.

2013 Novel Therapeutic Approach by Nicotine in Experimental Model of Multiple Sclerosis

  • Animal Study
  • Due to the proven therapeutic effect of nicotine on AD (Alzheimer’s Disease) and PD (Parkinson’s Disease), we decided to study the role of nicotine in EAE as an animal model of MS. Our treatment group showed less inflammation in histopathological evaluation along with myelin sheet protection. Moreover, prevention group showed less inflammation compared with treatment group. Thus, nicotine might be recommended as a promising drug for MS therapy.
  • PDF Version
  • Citation: Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci. 2013 Apr;10(4):20-5. PMID: 23696955; PMCID: PMC3659034.


Narcolepsy

2021: The therapeutic use of medical nicotine in narcolepsy

2012: Narcolepsy with Cataplexy Masked by the Use of Nicotine

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


Oral / Jaw

2021: Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study

  • HSC-2 cell viability was not impaired by nicotine at the concentrations usually observed in smokers; increased expressions of IL-8 and ICAM-1 induced by P. gingivalis LPS or TNF-α were diminished by nicotine treatment. Additionally, an inhibitory effect on β-defensin production was also demonstrated. Apart from being the usually alleged harmful substance, nicotine probably exerted a suppressive effect on inflammatory factors production in HSC-2 cells.
  • Acknowledgement: This research was supported by the grant from Ministry of Science and Technology of China under a contract from the International Science & Technology Cooperation Program Foundation Nr.1019 and the National Natural Science Foundation of China (Grant No. 81500859).
  • Citation: An, N., Holl, J., Wang, X., Rausch, M. A., Andrukhov, O., & Rausch-Fan, X. (2021). Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study. International Journal of Environmental Research and Public Health, 18(2), 483. https://doi.org/10.3390/ijerph18020483

2020 Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial

  • The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
  • This study establishes a new prevention and treatment modality regarding pain, oedema, and trismus in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
  • PDF Version
  • Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
  • Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

2012 Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program

  • The results of this study confirm that chewing the tested nicotine replacement gum as recommended in a ‘real world’ active smoking cessation program produces a statistically significant change in the parameter of whitening as measured by change from baseline versus the negative control (Microtab) following 6 weeks in a smoking cessation programme. The Vita® Shade Guide (the secondary outcome measure) supported the trend of stain improvement. These results support the efficacy of the tested nicotine replacement gum in stain reduction, in arresting the progression of tooth stain and in shade lightening.
  • Acknowledgement: The study was fully funded by McNeil AB who is the manufacturer of the test and control products. It was designed by McNeil AB in consultation with HW and DOM. The study was run, participants recruited, smoking cessation intervention administered and data collected by the team of research staff at the Oral Health Services Research Centre at University College Cork under the leadership of HW with consultant input from DOM. RK carried out the clinical examinations but was blinded to intervention allocation. The data were analysed by McNeil AB with input from HW and DOM. The study was externally monitored by MDS Pharma Services, UK and conducted to ICH GCP standards. The data were interpreted by HW, DOM and RK. The manuscript was drafted by HW with editorial comment from the other authors. HW decided to submit the manuscript for publication.
  • Citation: Whelton H, Kingston R, O'Mullane D, Nilsson F. Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program. BMC Oral Health. 2012 Jun 13;12:13. doi: 10.1186/1472-6831-12-13. PMID: 22695211; PMCID: PMC3444372.


Pain / Analgesic

2023: The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis

  • Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
  • Citation: Luo Y, Yang Y, Schneider C, Balle T. The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis. Pharmaceuticals. 2023; 16(12):1665. https://doi.org/10.3390/ph16121665
  • Acknowledgement: This work was funded by the Australian Research Council LP160100560.

2023 Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron

  • Animal Study
  • Nicotine-induced antinociception was inhibited by intrathecal pre-treatment with yohimbine, an α2 adrenergic receptor antagonist. These results indicated that nicotine may suppress BCAO-induced mechanical hypersensitivity through the activation of the descending pain control system via orexin neurons.
  • Citation: Nakamoto, K., Matsuura, W., & Tokuyama, S. (2023). Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron. European journal of pharmacology, 175518. Advance online publication. https://doi.org/10.1016/j.ejphar.2023.175518

2020 Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial

  • The positive findings in the present study in surgeries performed under local anaesthesia are in agreement with data from systematic reviews that have reported the effectiveness of nicotine in the control of postoperative pain following surgery under general anaesthesia.
  • This study establishes a new prevention and treatment modality regarding pain, oedema, and trismus in a versatile, convenient, safe, and effective form, thereby minimizing gastrointestinal and cardiovascular disorders caused by the use of anti-inflammatory drugs in third molar surgeries.
  • PDF Version
  • Citation: Landim FS, Laureano Filho JR, Nascimento J, do Egito Vasconcelos BC. Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int J Oral Maxillofac Surg. 2020 Nov;49(11):1508-1517. doi: 10.1016/j.ijom.2019.08.013. Epub 2020 May 4. PMID: 32381373.
  • Acknowledgements: Funding - CAPES, Ministry of Education, Brazil

2017 Acute Analgesic Effects of Nicotine and Tobacco in Humans: A Meta-Analysis

  • Pain and tobacco smoking are both highly prevalent and comorbid conditions, current smoking has been associated with more severe chronic pain and physical impairment, and acute nicotine-induced analgesia could make smoking more rewarding and harder to give up.
  • Moderation analyses further revealed that acute analgesic effects may be achieved regardless of nicotine delivery method, current smoking status, pain induction modality, study design, or control condition, and that such effects may be more robust among men than women.
  • PDF Version
  • Citation: Ditre JW, Heckman BW, Zale EL, Kosiba JD, Maisto SA. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain. 2016;157(7):1373-1381. doi:10.1097/j.pain.0000000000000572 (viewed Oct 5, 2021)
  • Acknowledgement: This research was supported by NIH Grant Nos. R21DA034285 and R21DA038204 awarded to Joseph W. Ditre, NIH Grant Nos. F31DA033058 and T32DA007288 awarded to Bryan W. Heckman, NIH Grant No. F31DA039628 awarded to Emily L. Zale, and NIH Grant No. 2K05 AA16928 awarded to Stephen A. Maisto.

2013 Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models

  • Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold.
  • Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli.
  • Intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the nAChR modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
  • PDF Version
  • Citation: Lorenzo Di Cesare Mannelli, Matteo Zanardelli, Carla Ghelardini, Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models, European Journal of Pharmacology, Volume 711, Issues 1–3, 2013, Pages 87-94, ISSN 0014-2999, doi: 10.1016/j.ejphar.2013.04.022.
  • Acknowledgements: This work was supported by the Italian Ministry of Instruction, University and Research.
  • Keywords: nAChR; Dideoxycytidine; Oxaliplatin; Antiviral; Anticancer, pain, chemotherapy, nicotine, neuropathy

2011 Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women

  • Intraoperative use of intranasal nicotine has a sustained opioid-sparing effect in non-smoking women undergoing gynaecological procedures and is associated with a higher frequency of nausea.
  • PDF Version
  • Citation: Jankowski, Christopher J.; Weingarten, Toby N.; Martin, David P.; Whalen, Francis X.; Gebhart, John B.; Liedl, Lavonne M.; Danielson, David R.; Nadeau, Ashley M.; Schroeder, Darrell R.; Warner, David O.; Sprung, Juraj Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women, European Journal of Anaesthesiology (EJA): August 2011 - Volume 28 - Issue 8 - p 585-591 doi: 10.1097/EJA.0b013e328344d998
  • Acknowledgements: The present work was supported solely by the Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

2008 Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy

  • The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in postoperative opioid consumption in nonsmoking men undergoing RRP in this study. Its use was generally well tolerated, but the maximum nausea scores were higher in patients who received nicotine.
  • PDF Version
  • Citation: Habib, Ashraf S., MBBCh, MSc, FRCA*; White, William D., MPH*; El Gasim, Magdi A., MD*; Saleh, Gamal, MD*; Polascik, Thomas J., MD†; Moul, Judd W., MD†; Gan, Tong J., MB, FRCA* Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy, Anesthesia & Analgesia: September 2008 - Volume 107 - Issue 3 - p 999-1004 doi: 10.1213/ane.0b013e31816f2616

2002 Isoflurane hyperalgesia is modulated by nicotinic inhibition

  • Animal study
  • Female mice had significant hyperalgesia from isoflurane. Nicotine administration prevented isoflurane-induced hyperalgesia without altering the antinociception produced by higher isoflurane concentrations.
  • Citation: Flood P, Sonner JM, Gong D, Coates KM. Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology. 2002 Jul;97(1):192-8. doi: 10.1097/00000542-200207000-00027. PMID: 12131122.
  • Acknowledgement: 1P01GM47818/GM/NIGMS NIH HHS/United States, K08GM00695/GM/NIGMS NIH HHS/United States


Parkinson Disease

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

  • This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction.
  • At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS.
  • We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.
  • Note: highly technical brain biochemistry, appears to be important however (ed.) Paper on the UPS and it's purpose for info.
  • Exp Brain Res. 2024 Mar 2. Inam Ullah, Shahab Uddin, Longhe Zhao, Xin Wang, Hongyu Li. PMID: 38430248 DOI: 10.1007/s00221-023-06765-9
  • Animal study (worms with humanised neurons)

2023: Changes in smoking, alcohol consumption, and the risk of Parkinson’s disease

  • A total of 3,931,741 patients were included.
  • Compared to the sustained non-smokers, sustained light smokers, sustained moderate smokers, and sustained heavy smokers had a lower risk of PD.
  • Compared to those who sustained non-drinking, sustained light drinkers, sustained moderate drinkers, and sustained heavy drinkers showed decreased risk of PD.
  • Among non-drinkers, those who started drinking to a light level were at decreased risk of PD. Among non-smoking and non-drinking participants, those who initiated smoking only, drinking only, and both smoking and drinking showed decreased risk of PD.
  • Smoking is associated with decreased risk of PD with a dose–response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.
  • Front. Aging Neurosci., 13 September 2023 Sec. Parkinson’s Disease and Aging-related Movement Disorders Volume 15 - 2023 | https://doi.org/10.3389/fnagi.2023.1223310

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

  • Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo.
  • Mouse study
  • Ruan S, Xie J, Wang L, Guo L, Li Y, Fan W, Ji R, Gong Z, Xu Y, Mao J, Xie J. Front Pharmacol. 2023 Feb 2;14:1088957. doi: 10.3389/fphar.2023.1088957. eCollection 2023. PMID: 36817162 Free PMC article.

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

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

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

  • While many reports suggest causality, and often this is a stretch at best, here the authors discuss what is needed to prove a causal relationship and satisfy those requirements.
  • It is a rare example of how you should approach causality, reading the text gives a clear account of the criteria the authors consider to prove causality, and how these are met.
  • In contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.
  • Benjamin Mappin-Kasirer, Hongchao Pan, Sarah Lewington, Jennifer Kizza, Richard Gray, Robert Clarke, Richard Peto First published May 5, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009437

2020 Dietary nicotine intake and risk of Parkinson disease: a prospective study

  • At 26 year follow-up, women with greater dietary nicotine intake had a lower risk of Parkinson Disease (PD) than those with lower intake. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea.
  • PDF Version
  • Citation: Chaoran Ma, Samantha Molsberry, Yanping Li, Michael Schwarzschild, Alberto Ascherio, Xiang Gao, Dietary nicotine intake and risk of Parkinson disease: a prospective study, The American Journal of Clinical Nutrition, Volume 112, Issue 4, October 2020, Pages 1080–1087, doi: 10.1093/ajcn/nqaa186
  • Acknowledgements: Supported by National Institute of Neurological Disorders and Stroke at the NIH grant 1R03NS093245-01A1 (to XG). The Nurses’ Health Study is supported by the NIH through grant UM1 CA186107. The Health Professionals Follow-up Study cohort is supported by the NIH through grant U01 CA167552.
  • Keywords: dietary nicotine, Parkinson disease, neurodegenerative disease

2016: Re-thinking nicotine and its effects

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

2007 Nicotinic receptors as CNS targets for Parkinson’s disease

  • Human and animal references
  • Analyzes results showing that chronic nicotine treatment improved striatal integrity and function.
  • PDF Version
  • Citation: Quik M, Bordia T, O'Leary K. Nicotinic receptors as CNS targets for Parkinson's disease. Biochem Pharmacol. 2007 Oct 15;74(8):1224-34. doi: 10.1016/j.bcp.2007.06.015. Epub 2007 Jun 17. PMID: 17631864; PMCID: PMC2046219.
  • Acknowledgements: This work was supported by NIH grants NS42091 and NS47162.

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

  • Nicotine may have therapeutic uses in the treatment of Parkinson's Disease.
  • Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
  • PDF Version
  • Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against Parkinson's Disease (other diseases mentioned in study)
  • PDF Version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.


Psoriasis

2012 Can nicotine use alleviate symptoms of psoriasis?

  • In light of recent data demonstrating that psoriasis is an immune-mediated disease, the possibility that novel anti-inflammatory treatments such as nicotine replacement therapy or analogues could have a beneficial effect on patients with psoriasis should be considered. This case described one such occasion in which it appeared that nicotine had a therapeutic effect on a patient’s psoriasis.
  • PDF Version
  • Citation: Staples J, Klein D. Can nicotine use alleviate symptoms of psoriasis? Can Fam Physician. 2012 Apr;58(4):404-8. PMID: 22611606; PMCID: PMC3325452.


Pyoderma Gangrenosum

2004 Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream

  • Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.
  • PDF Version
  • Citations:Patel GK, Rhodes JR, Evans B, Holt PJ. Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream. J Dermatolog Treat. 2004 Apr;15(2):122-5. doi: 10.1080/09546630310019364. PMID: 15204166.
  • Keywords: Pyoderma gangrenosum — Topical nicotine cream — Treatment

1998 Nicotine for Pyoderma Gangrenosum

  • Herein we describe a patient with pyoderma gangrenosum who responded twice to topical nicotine within 4 weeks and 3 months, respectively, without any adverse effects.
  • PDF Version
  • Citation: Wolf R, Ruocco V. Nicotine for Pyoderma Gangrenosum. Arch Dermatol. 1998;134(9):1071–1072. doi:10.1001/archderm.134.9.1071

1995 Successful treatment of pyoderma gangrenosum with nicotine chewing gum

  • We used nicotine chewing gum for the treatment of pyoderma gangrenosum with remarkable results. We strongly suggest that nicotine chewing gum may not only be beneficial in treating pyoderma gangrenosum but may also be useful in treating other skin disorders with prominent neutrophilic infiltrations such as Behcet's disease, Sweet disease, allergic vasculitis, and recurrent oral aphthae, the last of which is known to respond to smoking.
  • PDF Version
  • Citation: Kanekura T, Kanzaki T. Successful treatment of pyoderma gangrenosum with nicotine chewing gum. J Dermatol. 1995 Sep;22(9):704-5. doi: 10.1111/j.1346-8138.1995.tb03904.x. PMID: 8537562.


Sarcoidosis

2021 Promise of Nicotine as a Treatment for Pulmonary Sarcoidosis

2021 A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis

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

  • The immune phenotype of patients with symptomatic sarcoidosis treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
  • PDF Version
  • Citation: Mark W. Julian, MS; Guohong Shao, MD; Larry S. Schlesinger, MD; Qin Huang, MD; David G. Cosmar, BA; Nitin Y. Bhatt, MD; Daniel A. Culver, MD, FCCP; Robert P. Baughman, MD, FCCP; Karen L. Wood, MD, FCCP; and Elliott D. Crouser, MD - ORIGINAL RESEARCH DIFFUSE LUNG DISEASE| VOLUME 143, ISSUE 2, P461-470, FEBRUARY 01, 2013, DOI 10.1378/chest.12-0383
  • Acknowledgements: This work was supported by the American Thoracic Society and the Foundation for Sarcoidosis Research. © 2013 American College of Chest Physicians


Seizures / Epilepsy

2021 Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients

  • This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.
  • Citation: Brodtkorb E, Myren-Svelstad S, Knudsen-Baas KM, Nakken KO, Spigset O. Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients. Epilepsy Res. 2021 Oct 25;178:106792. doi: 10.1016/j.eplepsyres.2021.106792. Epub ahead of print. PMID: 34763266.

2021 Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy

  • Nevertheless, the two siblings reported here add to the small number of pediatric case reports regarding the successful use of nicotine patches in ADSHE.
  • Journal Pre-Proof PDF Version
  • Citation: Nguyen SM, Deering L, Nelson GT, McDaniel SS, Nicotine patch improved autosomal dominant sleep-related hypermotor epilepsy, Pediatric Neurology (2021), doi:10.1016/j.pediatrneurol.2021.07.006.

2020 Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants

  • "Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction."
  • "Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants."
  • Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031

2020 Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy

  • "Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions."
  • Citation: Lossius K, de Saint Martin A, Myren-Svelstad S, Bjørnvold M, Minken G, Seegmuller C, Valenti Hirsch MP, Chelly J, Steinlein O, Picard F, Brodtkorb E. Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy Behav. 2020 Apr;105:106944. doi: 10.1016/j.yebeh.2020.106944. Epub 2020 Feb 22. PMID: 32097883.

2012 Resolution of epileptic encephalopathy following treatment with transdermal nicotine

  • We report resolution of an epileptic encephalopathy by administration of transdermal nicotine patches in an adolescent with severe nonlesional refractory frontal lobe epilepsy. The 18.5‐year‐old female patient had refractory epilepsy from the age of 11. Recurrent electroencephalography (EEG) recordings showed mostly generalized activity, albeit with right frontal predominance. Almost all antiepileptic medications failed to provide benefit. She developed an encephalopathic state with cognitive decline. The nonlesional frontal lobe epilepsy and a family history of a cousin with nocturnal epilepsy with frontal origin suggested genetic etiology. Transdermal nicotine patches brought complete resolution of the seizures, normalization of the EEG, and a significant improvement in her thinking process and speech organization. Sequencing of the CHRNB2 and CHRNA4 genes did not detect a mutation. Transdermal nicotine patches should be considered in severe pharmacoresistant frontal lobe epilepsy.
  • PDF Version
  • Citation: Zerem, A., Nishri, D., Yosef, Y., Blumkin, L., Lev, D., Leshinsky‐Silver, E., Kivity, S. and Lerman‐Sagie, T. (2013), Resolution of epileptic encephalopathy following treatment with transdermal nicotine. Epilepsia, 54: e13-e15. doi: 10.1111/j.1528-1167.2012.03715.x

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

  • In this individual with refractory ADNFLE, nicotine had a therapeutic effect on seizures, and it may be useful to others with this disorder.
  • PDF Version
  • Citation: Willoughby, J.O., Pope, K.J. and Eaton, V. (2003), Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study. Epilepsia, 44: 1238-1240. doi: 10.1046/j.1528-1157.2003.58102.x-i1


Sleep Apnea

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against sleep apnea (other diseases / issues mentioned in study)
  • PDF Version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

1985: Nicotine: a different approach to treatment of obstructive sleep apnea

  • Reduced upper airway muscle activity may contribute to the occurrence of obstructive apneas during sleep. There is no uniformly successful treatment of these apneas, and it is possible that agents which increase upper airway muscle activity could reduce the occurrence of obstruction during sleep. Nicotine, a known stimulant of breathing, also increases the activity of muscles which dilate the upper airway proportionally more than it does ventilation. Hence, we evaluated the effect of nicotine on apneas during the first two hours of sleep in eight patients with sleep apnea syndrome. It was concluded that nicotine reduces apneas during the early hours of sleep, and this effect may be caused by its stimulating action on upper airway muscles.
  • PDF Version
  • Citation: Gothe B, Strohl KP, Levin S, Cherniack NS. Nicotine: a different approach to treatment of obstructive sleep apnea. Chest. 1985 Jan;87(1):11-7. doi: 10.1378/chest.87.1.11. PMID: 3965253.


Smoking Cessation / Preventing Relapse

Resource Doc: INNCO - Myth of the month: Ecigs and snus don’t help smokers quit

  • Links and conclusions of studies formatted to fit the character limits on Twitter

Myth: Alternative nicotine products don't help people stop smoking

  • This wiki page shows over 70 studies demonstrating these products help people stop smoking.


Spinal Cord Injury

2008 Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury

  • Animal Study
  • Primary impact to the spinal cord results in stimulation of secondary processes that potentiate the initial trauma. Recent evidence indicates that nicotine can exert potent antioxidant and neuroprotective effects in spinal cord injury (SCI).
  • The results of the present study indicate that iNOS is induced in the early stages of SCI, leading to increased nitration of protein tyrosine residues and potentiation of inflammatory responses. Microglial cells appear to be the main cellular source of iNOS in SCI. In addition, nicotine-induced anti-inflammatory effects in SCI are mediated, at least in part, by the attenuation of iNOS overexpression through the receptor-mediated mechanism. This data may have significant therapeutic implications for the targeting of nicotine receptors in the treatment of compressive spinal cord trauma.
  • PDF Version
  • Citation: Lee, M.‐Y., Chen, L. and Toborek, M. (2009), Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J. Neurosci. Res., 87: 937-947.doi.org/10.1002/jnr.21901
  • Acknowledgements: This work was supported in part by the Philip Morris External Research Program and the Kentucky Science and Engineering Foundation.
  • Key words: spinal cord injury; nicotine; neuronal nicotinic receptors; oxidative stress; inflammatory responses; nitric oxide synthase


Tourette's Syndrome

2012 Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond

  • The article presents a mini-review of studies on TS and depression over the past 25 years.
  • It summarizes the studies on the behavioral biology of the basal ganglia and its neurotransmitters.
  • It describes research with TS patients to evaluate the therapeutics of nicotine and mecamylamine.
  • PDF Version
  • Citation: Sanberg, P. R., Vindrola-Padros, C., & Shytle, R. D. (2012). Translating laboratory discovery to the clinic: From nicotine and mecamylamine to Tourette’s, depression, and beyond. Physiology & Behavior, 107(5), 801–808. doi:10.1016/j.physbeh.2012.06.023
  • Acknowledgement: Paul R. Sanberg and R. Douglas Shytle are inventors on patents related to technology described herein and licensed from the University of South Florida to Targacept, Inc. Because of the historical nature of this article, the authors included a number of self-citations required for a chronological discussion.

2004 Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome

  • In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 hours, but counteracted ERP-P300 signs of diminished attention seen 2 weeks following placebo treatment.
  • Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention.
  • PDF Version
  • Citation: Howson, A. L., Batth, S., Ilivitsky, V., Boisjoli, A., Jaworski, M., Mahoney, C., & Knott, V. J. (2004). Clinical and attentional effects of acute nicotine treatment in Tourette’s syndrome. European Psychiatry, 19(2), 102–112. doi:10.1016/j.eurpsy.2003.11.002
  • Acknowledgement: This study was supported with a grant from the Tourette Syndrome Association (USA), and patient recruitment was aided by the Ottawa chapter of the Tourette Syndrome Foundation of Canada.

2001 Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study

  • Transdermal nicotine (TNP) was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder
  • PDF Version
  • Citation: Silver AA, Shytle RD, Philipp MK, Wilkinson BJ, McConville B, Sanberg PR. Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study. J Clin Psychiatry. 2001 Sep;62(9):707-14. doi: 10.4088/jcp.v62n0908. PMID: 11681767.

1997 Nicotine for the treatment of Tourette's syndrome

  • Within 24 hr of the application of a single 7-mg TNP (nicotine patch), the severity and frequency of tic symptoms is significantly decreased over baseline. This response is rapid, often reaching its maximum in the first 3 hr after application of a single patch. The duration of therapeutic effect of a single 7-mg TNP is variable and may last for about l-2 weeks.
  • Application of a 7-mg TNP to children and adolescents with TS appears to be clinically safe, with transient side effects. However, no child under 8 years of age and weighing less than 25 kg was considered for TNP treatment.
  • PDF Version
  • Citation: Paul R. Sanberg, Archie A. Silver, R.Doug Shytle, Mary Katherine Philipp, David W. Cahill, Harold M. Fogelson, Brian J. McConville, Nicotine for the treatment of Tourette's syndrome, Pharmacology & Therapeutics, Volume 74, Issue 1, 1997, Pages 21-25, ISSN 0163-7258, doi.org/10.1016/S0163-7258(96)00199-4.
  • Acknowledgements-This review was supported, in part, by grants from the Tourette Syndrome Association, The National Institute of Neurological Disease and Stroke (ROl NS 32067sOlAl) and the Smokeless Tobacco Research Council.
  • Keywords: Nicotine; Tourette's syndrome; tics; neuropsychiatric disorders

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

  • nicotine may have therapeutic uses in the treatment of Gilles de la Tourette’s syndrome (TS).
  • Drug companies have often refused to fund legitimate and valid research into the potential therapeutic use of nicotine owing to its association with smoking and its image of an abusable drug. Many in the health profession fail to acknowledge the evidence which suggests that nicotine may have potential therapeutic value.
  • PDF Version
  • Citation: Birtwistle J, Hall K. Does nicotine have beneficial effects in the treatment of certain diseases? Br J Nurs. 1996 Oct 24-Nov 13;5(19):1195-202. doi: 10.12968/bjon.1996.5.19.1195. PMID: 9006184.

1996 Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome

  • Sixteen Tourette's syndrome patients, aged 9 to 15 years, whose symptoms were not controlled with neuroleptics, were followed for various lengths of time after the application of one 7 mg transdermal nicotine patch (TNP) for 24 hours. While there was a broad range in individual response, application of the TNP produced significant reductions in Yale Global Tic Severity Scale (YGTSS) scores relative to baseline, with an average duration of effect lasting between 1 and 2 weeks. Side effects, for the most part, were transient.
  • Eleven patients had greater percentage changes after the second TNP than after the first TNP
  • PDF Version
  • Citation: Silver AA, Shytle RD, Philipp MK, Sanberg PR. Case study: long-term potentiation of neuroleptics with transdermal nicotine in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1996 Dec;35(12):1631-6. doi: 10.1097/00004583-199612000-00015. PMID: 8973070.

1992 The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder

  • In this study, nicotine markedly potentiated haloperidol effects in treating TD, and showed lesser effects on TD when used alone.
  • PDF Version
  • Citation: McConville BJ, Sanberg PR, Fogelson MH, King J, Cirino P, Parker KW, Norman AB. The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder. Biol Psychiatry. 1992 Apr 15;31(8):832-40. doi: 10.1016/0006-3223(92)90315-q. PMID: 1643197.
  • Acknowledgements: Supported in part by grants from the Smokeless Tobacco Research Council, Inc., the Tourette Syndrome Association, and Merrell Dow Pharmaceuticals. The authors thank Roger Stuebing, B.S.M.E., M.S.I.E., and Sunny Y. Lu, M.D., Ph.D. for statistical advice and Merrell Dow Pharmaceuticals for supplying both Nicoreue® gum and placebo nicotine gum.

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in: protection against Tourette's disease (other diseases mentioned in study)
  • PDF Version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.

1989 Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders

  • Chewing nicotine gum produced striking relief from tics and other symptoms of Tourette syndrome not controlled by neuroleptic treatment alone. It appears that the use of nicotine or cannabinoids may greatly improve the clinical response to neuroleptics in motor disorders.
  • PDF Version
  • Citation: D.E. Moss, Patricia Z. Manderscheid, S.P. Montgomery, Andrew B. Norman, Paul R. Sanberg, Nicotine and cannabinoids as adjuncts to neuroleptics in the treatment of tourette syndrome and other motor disorders, Life Sciences, Volume 44, Issue 21, 1989, Pages 1521-1525, ISSN 0024-3205, doi.org/10.1016/0024-3205(89)90444-X.
  • Acknowledgements: Supported in part by NIMH (RR 08012) and NIDA. Levonantradol and fluphenazine HCL were generous gifts from Pfizer Pharmaceuticals (Groton, Conn.) and E.R. Squibb and Sons (Princeton, N.J.), respectively.


Weight Loss / Appetite Control / Metabolism / Obesity

2011 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

  • Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.
  • Low-grade inflammation is a key feature of obesity and links obesity to insulin resistance, impaired glucose tolerance and even diabetes.
  • Overall, these findings suggest that nicotine and specific α7nAChR agonists may be beneficial in the prevention and treatment of obesity-induced inflammation and insulin resistance. However, there is also evidence that heavy smoking affects body fat distribution that is associated with central obesity and insulin resistance. Moreover, smoking appears to aggravate insulin resistance in persons with type 2 diabetes and to impair glycemic control.
  • Much work remains in terms of understanding the anti-inflammatory effects of nicotine in obesity-related inflammation and ulcerative colitis. However, it is now known that the α7nAChR plays a major role in the anti-inflammatory effects of nicotine and nicotine attenuates inflammation in both obesity and ulcerative colitis. Since the inflammatory response is an integral process in both obesity and ulcerative colitis, controlling the inflammatory response could ameliorate tissue damage.
  • Acknowledgement: This development of this work was supported by the Global Neuroscience Initiative Foundation (GNIF).
  • Citation: Lakhan, S.E., Kirchgessner, A. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9, 129 (2011). https://doi.org/10.1186/1479-5876-9-129

1991 Beneficial effects of nicotine

  • When chronically taken, nicotine may result in reduction of body weight
  • PDF version
  • Citation: Jarvik ME. Beneficial effects of nicotine. Br J Addict. 1991 May;86(5):571-5. doi: 10.1111/j.1360-0443.1991.tb01810.x. PMID: 1859921.
  • Acknowledgement: Supported by U. C. Tobacco-related Disease program, grant # RT87 and a grant from the John D. and Catherine T. MacArthur Foundation.


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