Nicotine therapeutic benefits

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Studies, Surveys, Papers, and Case Studies

• Sometimes it's necessary to view the PDF version to access the full study.
• This page is for referencing possible therapeutic (medicinal) benefits of nicotine.

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.

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.

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.

Alzheimer / Dementia / 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

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

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.

Autism

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.

Cognitive / IQ

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

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.

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

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.

Digestive Tract / Bowel

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

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

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.

Mental Health - ADD / ADHD / Attention

• Attention Deficit Hyperactivity Disorder (ADHD) - Information from NAMI
• Is ADHD a mental illness?
  • Mental illness is a very broad term. It refers to any type of condition that affects a person’s behavior, mood, or thinking.
  • Technically a mental illness, few practitioners use the words “mental illness” to describe kids with ADHD. They tend to refer to it as a “behavior disorder.” Some might even refer to it as a learning difference that can affect all areas of learning.
• The difference between ADD and ADHD
• A more accurate definition of ADD/ADHD is that it's a neurodevelopmental disorder. Viewing it as a "behavior disorder" is stigmatizing and misleading. People with ADHD are not making a choice to behave differently than NT people.

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.

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.

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.

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.

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.

Mental Health - Behavior Issues

• See Also: Mental Health - 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

Does nicotine help people with depression? Does nicotine cause depression?

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.

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.

• PDF Version
• Citation:

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 - 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

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

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.

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

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.

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.

Oral / Jaw

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

Pain / Analgesic

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

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

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

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.

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
• Acknowledgments: We thank Dr. Marcio Sotero De Menezes for suggesting the nicotine patch treatment in our patient following resolution of epilepsy in his patient with a similar presentation.
• Key Words: Autosomal dominant nocturnal frontal lobe epilepsy, Nicotinic acetylcholine receptors, Refractory epilepsy.

2003 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
• Acknowledgments: The Pharmacy Department undertook randomization and allocation of the trial phase. Nicotine patches and matching placebo patches were provided through SmithKlineBeecham Consumer Healthcare Australia. The patient was cooperatively conscientious in her documentation of seizures. Dr. Stephen Johnson provided helpful comments on nicotinic receptor pharmacology.

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 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

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.

Suggested studies to add to this page

2012: Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

• Animal

2021: Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS

• mouse study

2021: Interventions for preventing weight gain after smoking cessation

• There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.

2017 Moist smokeless tobacco (Snus) use and risk of Parkinson's disease

• Smoke-free nicotine appears to reduce the risk of Parkinson’s disease by 60%.
• different website same study? [Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease|https://academic.oup.com/ije/article/46/3/872/2656164]

2010 Meta-analysis of the acute effects of nicotine and smoking on human performance and 2012 Nicotine treatment of mild cognitive impairment A 6-month double-blind pilot clinical trial

• Clinical studies suggest some cognitive improvements as a result of nicotine.

INNCO's List smoking cessation

Started: continue @ “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT products [i.e., nicotine patches, gum or lozenges].” https://onlinelibrary.wiley.com/doi/full/10.1111/add.12623

More Information

• List of researchers studying nicotine / tobacco harm reduction

• If you'd prefer someone else to add a study to a topic, there is a "topic" called "Suggested studies to add to this page". You may put the link in that section for one of the regular page editors to address.

• PAGE EDITORS - Please only add Studies, Surveys, Papers in this format to keep page consistent for all viewers.
  • Topic
  • Note here if animal study (leave blank if not)
  • Year (list new to old) Name of Study (In link format to the study)
  • Brief Summary
  • Link to PDF Version
  • Citation
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