Nicotine therapeutic benefits

Studies, Surveys, Papers, and Case Studies

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Addiction

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

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

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

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.

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

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.

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.

Downs 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

Mental Health - ADD/ADHD

• 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

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.

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.
• Keywords: Nicotine, Cholinergic, ADHD, Cognition, Behavioral inhibition, Delay aversion, Methylphenidate, Stop Signal Task, Impulsivity

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.
• Keywords: ADHD, Transdermal nicotine, CPT, WCST, Stroop, Attention, Memory

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

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.

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.

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

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.

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

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

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

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.

Smoking Cessation - E-cigarette (ENDS/ANDS) vs. NRT OR E-cigarette with NRT

2021: Electronic cigarettes in standard smoking cessation treatment by tobacco counselors in Flanders: E-cigarette users show similar if not higher quit rates as those using commonly recommended smoking cessation aids

• One third of the total sample was biochemically verified smoking abstinent 7 months after quit date, with e-cigarette users (40%) having significantly higher chances to be smoking abstinent than NRT users (23%).
• PDF Version
• Citation: Adriaens, K., Belmans, E., Van Gucht, D. et al. Electronic cigarettes in standard smoking cessation treatment by tobacco counselors in Flanders: E-cigarette users show similar if not higher quit rates as those using commonly recommended smoking cessation aids. Harm Reduct J 18, 28 (2021). https://doi.org/10.1186/s12954-021-00475-7
• Acknowledgement: This research received no external funding. EB is supported by a PhD-fellowship of the Research Foundation – Flanders (FWO-Vlaanderen; 1177820N).

2020: QuitNic: A pilot randomised controlled trial comparing nicotine vaping products with nicotine replacement therapy for smoking cessation following residential detoxification

• This pilot study showed that smoking cessation support involving options for nicotine replacement and Quitline-delivered cognitive behavioural counselling is attractive to people after they have been discharged from SUD (Substance Use Disorder) treatment.
• Retention was 63% at 6-weeks and 50% at 12-weeks. At 12-weeks, 68% of the NRT group reported using combination NRT while 96% of the NVP group used the device. Acceptability ratings for the products were high in both groups. At 12-weeks, 14% of the NVP group and 18% of the NRT group reported not smoking at all in the last 7 days. Mean CPD (Cigarettes Per Day) among continued smokers decreased significantly between baseline to 12-weeks in both groups; from 19.91 to 4.72 for the NVP group (p<0.001) and from 20.88 to 5.52 in the NRT group (p<0.001). Cravings and withdrawal symptoms significantly decreased for both groups.
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2020: Effectiveness of Electronic Cigarettes in Smoking Cessation: a Systematic Review and Meta-Analysis

• Our results suggest that nicotine-ECs may be more effective in smoking cessation when compared to placebo ECs or NRT.
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2019: E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT

• The primary outcome was CO-validated sustained abstinence rates at 52 weeks. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers.
• The 1-year quit rate was 9.9% in the NRT arm and 18.0% in the e-cigarette arm.
• The e-cigarette arm had significantly higher validated quit rates at all time points. Participants in the e-cigarette arm showed significantly better adherence and experienced fewer urges to smoke throughout the initial 4 weeks of their quit attempt than those in the NRT arm, and gave their allocated product more favourable ratings. They were also more likely to be still using their allocated product at 1 year
• Participants assigned to e-cigarettes reported significantly less coughing and phlegm at 1 year than those assigned to NRT
• A detailed economic analysis confirmed that, because e-cigarettes incur lower NHS costs than NRT and generate a higher quit rate, e-cigarette use is more cost-effective.
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2019: Cost‐effectiveness of e‐cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial

• Using e‐cigarettes as a smoking cessation aid with standard behavioural support in stop‐smoking services in England is likely to be more cost‐effective than using nicotine replacement therapy in the same setting.
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2019: Effect of Electronic Cigarettes on Smoking Reduction and Cessation in Korean Male Smokers: A Randomized Controlled Study

• In our study, the effect of e-cigarettes on smoking cessation was similar compared with that of nicotine gum, a well-documented NRT. In addition, e-cigarettes were well tolerated by the study population. Therefore, the use of e-cigarettes as an NRT may be considered for smoking-cessation purposes.
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2019: A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy

• A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.
• Conclusion: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support.
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2019: Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial

• In summary, when looking at continuous abstinence from smoking, provision of patches plus a nicotine e-cigarette resulted in three to seven more smokers per 100 quitting long-term (depending on the analyses done) than with patches plus a nicotine-free e-cigarette. The smaller than anticipated sample size meant the study was not sensitive enough to pick up a definitive finding for the second comparison, although analyses suggest combination nicotine therapy—ie, use of a slow release nicotine patch, together with a faster-acting oral nicotine product (in this case a nicotine e-cigarette)—could result in five to ten more smokers per 100 quitting long-term than with monotherapy (ie, nicotine patches alone). Our findings are consistent with the current findings of the Cochrane review of e-cigarettes for smoking cessation and contribute to the growing body of evidence from randomised trials on the efficacy, effectiveness and safety of e-cigarettes for smoking cessation.
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2018: American Cancer Society Position Statement on Electronic Cigarettes

• Based on currently available evidence, using current generation e-cigarettes is less harmful than smoking cigarettes, but the health effects of long-term use are not known.
• The ACS has always supported any smoker who is considering quitting, no matter what approach they use; there is nothing more important that they can do for their health. Some smokers, despite firm clinician advice, will not attempt to quit smoking cigarettes and will not use FDA approved cessation medications. These individuals should be encouraged to switch to the least harmful form of tobacco product possible; switching to the exclusive use of e- cigarettes is preferable to continuing to smoke combustible products.

2018: Discussions between health professionals and smokers about nicotine vaping products: results from the 2016 ITC Four Country Smoking and Vaping Survey

• Despite the need for more evidence on their efficacy and long‐term safety, NVPs are now a more popular method for cessation than licensed NRT and prescription stop‐smoking medications in many countries.
• In light of this, HPs should be prepared to provide balanced information about NVPs, particularly to smokers who are unable to stop smoking with approved cessation therapies, and for those who are requesting guidance regarding NVPs as a smoking cessation aid
• Overall, the results from this study have shown that discussions between smokers and HPs about both quitting smoking, and the possible role NVPs could play as a cessation aid, were infrequent in the four countries in 2016. This may represent a lost opportunity for encouraging quitting smoking by providing a potentially attractive option to help smokers to quit.
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2016: E-cigarettes: a developing public health consensus

• From: Public Health England, Action on Smoking and Health, Association of Directors of Public Health, British Lung Foundation, Cancer Research UK, Faculty of Public Health, Fresh North East, Healthier Futures, Public Health Action, Royal College of Physicians, Royal Society for Public Health, UK Centre for Tobacco and Alcohol Studies, UK Health Forum
• We all agree that e-cigarettes are significantly less harmful than smoking. One in two lifelong smokers dies from their addiction. All the evidence suggests that the health risks posed by e-cigarettes are relatively small by comparison but we must continue to study the long-term effects.
• And yet, millions of smokers have the impression that e-cigarettes are at least as harmful as tobacco
• The public health opportunity is in helping smokers to quit, so we may encourage smokers to try vaping but we certainly encourage vapers to stop smoking tobacco completely.
• We know that e-cigarettes are the most popular quitting tool in the country with more than 10 times as many people using them than using local stop smoking services
• The current national evidence is that in the UK regular e-cigarette among youth use is almost exclusively confined to those young people who have already smoked, and youth smoking prevalence is continuing to fall

We should not forget what is important here. We know that smoking is the number one killer in England and we have a public health responsibility to provide smokers with the information and the tools to help them quit smoking completely and forever.

2014: Real-world effectiveness of e-cigarettes when used to aid smoking cessation: a cross-sectional population study

Conclusion: “Among smokers who have attempted to stop without professional support, those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT product bought over-the-counter or no aid to cessation. This difference persists after adjusting for a range of smoker characteristics such as nicotine dependence.”

2014: E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices

Related Article: E-Cigarettes vs. Nicotine Inhalers “In conclusion, during this brief trial, the e-cigarette was found to be more acceptable, provided more satisfaction and rewards, and had higher perceived benefit than the nicotine inhaler. These findings may explain why the e-cigarette has become popular among smokers while the inhaler has not achieved the same favorability. Based on this difference, e-cigarettes could have the potential to become “tobacco cigarette substitutes,” owing to their high acceptance and perceived effectiveness. While toxicants have been identified in e-cigarettes, they are present at orders of magnitude lower than tobacco cigarettes. As such, e-cigarettes may hold value as a harm reduction strategy among those unwilling or unable to quit. However, given the large variation in the market with respect to brands, more data are needed to demonstrate their efficacy and safety, and to allow physicians to more appropriately inform their patients about these products.”

2013: Electronic cigarettes for smoking cessation: a randomised controlled trial

657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes

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

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

2013: Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review

When compared to the harmful effects of smoking, these studies suggest that vaping could be used as a possible “harm reduction” tool. There is evidence supporting e-cigarettes as an aide for smoking cessation, at least as successful as currently available FDA-approved NRTs.

2011: Successful smoking cessation with electronic cigarettes in smokers with a documented history of recurring relapses: a case series

The most important message from this case series is that these smokers, with a documented history of recurring relapses, were able to quit smoking and to remain abstinent for at least six months after taking up an electronic cigarette.

Smoking Cessation / Preventing Relapse - E-cigarette (ENDS/ANDS) - Stand Alone

2020: Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session

In E3, nicotine e-cigarettes plus counseling was superior to counseling alone for smoking cessation. Non-nicotine e-cigarettes plus counseling was also more effective compared with counseling alone though its effects on cessation were modest. This trial demonstrates the efficacy of e-cigarettes as a tool for smoking cessation compared with counseling alone.

2020: A magic bullet? The potential impact of e-cigarettes on the toll of cigarette smoking

The combination of assumptions produces 360 possible scenarios. 357 (99%) yield positive estimates of life-years saved (LYS) due to vaping by 2100, from 143,000 to 65 million. The impact of vaping is greatest when it most helps smokers who otherwise have the greatest difficulty quitting smoking. Vaping is highly likely to reduce smoking-produced mortality. Still, vaping is not “the” answer to the public health crisis created by smoking. Rather, it may well be a tool to add to the armamentarium of effective tobacco control measures. Harm reduction can, and many would say should, be a part of the complex formula that will eventually bring about the demise of smoking.

2020: Patterns of e-cigarette use and subsequent cigarette smoking cessation over two years (2013/2014 to 2015/2016) in the Population Assessment of Tobacco and Health (PATH) Study

• Smoking cessation was more likely among frequent e-cigarette users, users of e-cigarettes in last quit attempt, and users of flavored and rechargeable devices.
• In this study, the proportion of US adults who incorrectly perceived e-cigarettes as equal to, or more, harmful than cigarettes increased steadily regardless of smoking or vaping status. Current adult smokers appear to be poorly informed about the relative risks of e-cigarettes yet have potentially the most to gain from transitioning to these products. The findings of this study emphasise the urgent need to accurately communicate the reduced relative risk of e-cigarettes compared to continued cigarette smoking and clearly differentiate absolute and relative harms.
• The lack of accurate and consistent messaging from both public health agencies and the media may be contributing to public, and more specifically adult smokers’, perceptions about the relative risk of nicotine when decoupled from combustion and tobacco smoke.
• Confusion may potentially be discouraging adult smokers from using alternative, less hazardous products which may ultimately result in a missed opportunity to positively impact health at both an individual and population level.
• PDF Version
• Citation: Allison M Glasser, MPH, Mahathi Vojjala, MPH, Jennifer Cantrell, DrPH, MPA, David T Levy, PhD, Daniel P Giovenco, PhD, MPH, David Abrams, PhD, Raymond Niaura, PhD, Patterns of E-cigarette Use and Subsequent Cigarette Smoking Cessation Over 2 Years (2013/2014–2015/2016) in the Population Assessment of Tobacco and Health Study, Nicotine & Tobacco Research, , ntaa182, doi: 10.1093/ntr/ntaa182
• Acknowledgement: The paper was funded by Imperial Brands Plc.

2020: Using e-cigarettes for smoking cessation: evaluation of a pilot project in the North West of England

Of the 1022 participants who engaged with the pilot 614 were still engaged at 4 weeks, of whom 62% had quit smoking. Of those who still smoked tobacco at week 4, smoking had reduced from a baseline of 19.1 cigarettes/day to 8.7. Overall, 37% of those initially enrolled were confirmed to be using an e-cigarette on its own at follow-up. Successful quit was associated with occupation (unemployed, 33% vs intermediate, 47%) and residing in the less deprived quintiles of deprivation (50% vs 34% in the most deprived quintile. E-cigarettes appear to be an effective nicotine replacement therapy

2020: Tobacco harm reduction in the 21st century

In conclusion, to reduce smoking and to save millions of lives, tobacco harm reduction in the form of cigarette substitution with low-risk products appears to be a promising path. These products, although not completely risk-free, offer an alternative to quit or die. In consideration of the available evidence, advice to tobacco smokers should include trying substitute products. The obvious fact so often overlooked is that smoking is rewarding and people like to do it. Giving smokers an alternative with efficient nicotine delivery means that they might prefer one of these products over cigarettes.

2019: Association Between Electronic Cigarette Use and Smoking Reduction in France

Findings This cohort study found that, among daily smokers in France, regular (daily) electronic cigarette use is associated with a significantly higher decrease in the number of cigarettes smoked per day as well as an increase in smoking cessation attempts. However, among former smokers, electronic cigarette use is associated with an increase in the rate of smoking relapse. NOTE: Article that covers above study - Adults who vape are more likely to quit cigarettes, study finds “The study did find that the heightened risk of relapse disappeared in those who quit smoking more recently, which the researchers said may be due to improved e-cigarette technology.” “For example, the study as a whole considered anybody who quit smoking from 2010 onward and found that, in that sample, vaping increased the risk of relapse. But when researchers only considered people who quit cigarettes as of 2013, former smokers were not more likely to relapse if they vaped.” “The researchers noted in their study that "measures of plasma nicotine levels have shown that, compared with older models of [e-cigarettes], the new generation delivers higher levels of nicotine to the bloodstream," which may make them more satisfying.” “Other "technical improvements in [e-cigarettes] over time," they said, may also explain why people who recently quit smoking and switched to e-cigarettes were less likely to relapse than those who quit earlier.”

2019: Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time–series analysis between 2007 and 2017

The increase in prevalence of e‐cigarette use by smokers in England has been positively associated with an increase in success rates of quit attempts and overall quit rates

2019 Electronic Cigarette Use and Cigarette Abstinence Over 2 Years Among U.S. Smokers in the Population Assessment of Tobacco and Health Study

In this nationally representative longitudinal cohort study of US adult cigarette smokers, daily e-cigarette use, compared to no e-cigarette use, was associated with a 77% increased odds of prolonged cigarette smoking abstinence over the subsequent 2 years. Regular use of e-cigarettes may help some smokers to stop smoking combustible cigarettes. Article: Daily e-cigarette use may help smokers quit regular cigarettes

2019 Article: Adults who vape are more likely to quit cigarettes, study finds

“The study did find that the heightened risk of relapse disappeared in those who quit smoking more recently, which the researchers said may be due to improved e-cigarette technology.” “For example, the study as a whole considered anybody who quit smoking from 2010 onward and found that, in that sample, vaping increased the risk of relapse. But when researchers only considered people who quit cigarettes as of 2013, former smokers were not more likely to relapse if they vaped.” “The researchers noted in their study that "measures of plasma nicotine levels have shown that, compared with older models of [e-cigarettes], the new generation delivers higher levels of nicotine to the bloodstream," which may make them more satisfying.” “Other "technical improvements in [e-cigarettes] over time," they said, may also explain why people who recently quit smoking and switched to e-cigarettes were less likely to relapse than those who quit earlier.”

2018 Advice From Former-Smoking E-Cigarette Users to Current Smokers on How to Use E-Cigarettes as Part of an Attempt to Quit Smoking

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

2017: Predicting Short-Term Uptake of Electronic Cigarettes: Effects of Nicotine, Subjective Effects, and Simulated Demand

Mean cigarettes per day decreased by 37% when e-cigarettes were available relative to baseline. Nicotine-containing cartridges were associated with greater use and craving reduction than 0 mg. Alleviation of withdrawal symptoms and taste and enjoyment factors predicted e-cigarette use.

2017: Cohort study of electronic cigarette use: effectiveness and safety at 24 months

Of the e-cigarette users, 61.1% remained abstinent from tobacco (while 23.1% and 26.0% of tobacco-only smokers and dual users achieved tobacco abstinence).

2016: Patterns of Electronic Cigarette Use Among Adults in the United States

Results: Current e-cigarette use is extremely low among never cigarette smokers (0.4%) and former smokers who quit cigarettes 4 or more years ago (0.8%). Although e-cigarette experimentation is most common among current cigarette smokers and young adults, daily use is highest among former smokers who quit in the past year (13.0%) and older adults. Compared to daily cigarette smokers, recently quit smokers were more than four times as likely to be daily users of e-cigarettes ( AOR : 4.33 [95% CI: 3.08–6.09]). Conclusion: Extremely low e-cigarette use among never-smokers and longer term former smokers suggest that e-cigarettes neither promote widespread initiation nor relapse among adults. Recognition of the heterogeneity of smokers, including the time since quitting, is critical to draw accurate conclusions about patterns of e-cigarette use at the population level and its potential for public health benefit or harm.

2016: Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries

E‐cigarette use in the European Union appears to be largely confined to current or former smokers, while current use and nicotine use by people who have never smoked is rare. More than one‐third of current e‐cigarette users polled reported smoking cessation and reduction.

2015: E-Cigarettes and Smoking Cessation: Evidence from a Systematic Review and Meta-Analysis

Conclusions: “This systematic review and meta-analyses assessed the findings of six studies which reported smoking cessation after using e-cigarettes. We found an association between nicotine-enriched e-cigarette use and smoking cessation, suggesting that the devices may be an effective alternative smoking cessation method. We also found that use of e-cigarettes was also associated with a reduction in the number of cigarettes used, suggesting they may also have a role in tobacco harm reduction programs. To our knowledge, this is the most comprehensive evidence to date on this issue, and while there are a number of important implications for further research, these findings provide timely information to inform regulatory strategies.”

2015: A Longitudinal Study of Electronic Cigarette Use Among a Population-Based Sample of Adult Smokers: Association With Smoking Cessation and Motivation to Quit

Results: At follow-up, 23% were intensive users, 29% intermittent users, 18% had used once or twice, and 30% had not tried e-cigarettes. Logistic regression controlling for demographics and tobacco dependence indicated that intensive users of e-cigarettes were 6 times more likely than non-users/triers to report that they quit smoking (OR: 6.07, 95% CI = 1.11, 33.2). No such relationship was seen for intermittent users. There was a negative association between intermittent e-cigarette use and 1 of 2 indicators of motivation to quit at follow-up. Conclusion: Daily use of electronic cigarettes for at least 1 month is strongly associated with quitting smoking at follow-up. Further investigation of the underlying reasons for intensive versus intermittent use will help shed light on the mechanisms underlying the associations between e-cigarette use, motivation to quit, and smoking cessation.

2015: Associations Between E-Cigarette Type, Frequency of Use, and Quitting Smoking: Findings From a Longitudinal Online Panel Survey in Great Britain

Conclusion: Whether e-cigarette use is associated with quitting depends on type and frequency of use. Compared with respondents not using e-cigarettes, daily tank users were more likely, and non-daily cigalike users were less likely, to have quit. Tanks were more likely to be used by older respondents and respondents with lower education.

2015: Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study (PDF 14 pages)

Results: Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers...

2014: Effectiveness of the Electronic Cigarette: An Eight-Week Flemish Study with Six-Month Follow-up on Smoking Reduction, Craving and Experienced Benefits and Complaints

When people, ready to switch to an e-cig, are severely restricted in terms of accessibility of nicotine-containing e-liquids, the success of e-cigs may be endangered. For the e-cig to be and remain successful, it is important that people have easy access to nicotine containing e-liquids. Conclusion: “In a series of controlled lab sessions with e-cig-naïve tobacco smokers, second-generation e-cigs were shown to be immediately and highly effective in reducing abstinence-induced cigarette craving and withdrawal symptoms, while not resulting in increases in eCO. Ad libitum use of e-cigs—in between and until six months after the lab sessions—resulted in remarkable reductions in or (biologically confirmed) complete abstinence from tobacco smoking in almost half of the participants who had no intention to quit smoking. [highlighting added] Eight months after the start of the study 21% of all participants were completely abstinent from tobacco cigarettes. Similar reduction/cessation rates were obtained with guided versus non-guided switching to e-cigs. Part of the observed efficacy of e-cigs in this study may be related to the fact that they allowed to maintain relatively high blood nicotine levels and showed an excellent experienced benefits/complaints ratio, especially in comparison with continued tobacco smoking”... E-cigarette is an attractive long-term alternative and safer source of nicotine to conventional cigarette. Since their invention in 2003, there has been constant innovation and development of more efficient and appealing products. Here we show for the first time that second generation PVs can substantially decrease cigarette consumption without causing significant side effects in smokers not intending to quit. Moreover, overall participants’ perception and acceptance of these products was very good, in particular for those who quit or reduced smoking. Compared to our earlier work with first generation “cig-alikes”, technical problems and difficulties in use familiarization with second generation PVs were negligible. Improved products reliability and attractiveness might have contributed to the very low number of study failures and lost to follow-up and high success rates thus confirming the notion that these products are attractive substitutes for conventional cigarettes. Although large and carefully conducted RCTs will be required to confirm these preliminary encouraging observations, the notion that second generation PVs can substantially decrease cigarette consumption in smokers not intending to quit should be taken into consideration by regulatory authorities seeking to adopt proportional measures for the vapour category

2014: Success rates with nicotine personal vaporizers: a prospective 6-month pilot study of smokers not intending to quit

Complete tobacco cessation is the best outcome for smokers, but the powerful addictive qualities of nicotine and of the ritualistic behavior of smoking create a huge hurdle, even for those with a strong desire to quit. Tobacco harm reduction (THR), the substitution of low-risk nicotine products for cigarette smoking, is a realistic strategy for smokers who have difficulty quitting. E-cigarettes are the newest and most promising products for THR. This approach has been recently exploited to reduce or reverse the burden of harm in smokers with mental health disorders and chronic airway disease.

2014: Characteristics, Perceived Side Effects and Benefits of Electronic Cigarette Use: A Worldwide Survey of More than 19,000 Consumers

The main results of this survey indicate that ECs may be an effective substitute for smoking even in highly dependent subjects who are heavy smokers. Significant benefits are experienced by these people in physiologic functions and in some disease conditions, with former smokers (those who completely substituted smoking with EC use) being more likely to report such beneficial effects. Both former and current smokers initiated EC use with high nicotine-containing liquids. More than one-fifth of the population initiated use with more than 20 mg/mL nicotine concentration, with higher prevalence in former smokers, supporting the hypothesis that nicotine plays an important role in the success of ECs as smoking substitutes [4,16]. This can be attributed to the lower nicotine absorption from EC use compared to smoking [13,17,18]. Such repeated observations should be taken into consideration by the regulatory authorities. The most important reasons for participants to initiate ECs were to reduce or completely quit smoking and to reduce exposure of family members to second-hand smoking. It seems that these subjects are well-informed about the adverse health effects of smoking and are willing to try an alternative product which they consider less harmful. In conclusion, in this large sample of dedicated EC users, it seems that ECs are used as long-term substitutes to smoking. They can be effective even in subjects who are highly dependent on smoking and are heavy smokers. Mild temporary side-effects and significant benefits are reported by this population. Motivation for using ECs comes from their expected less harmful potential compared to smoking.

2014: Reasons for quitting cigarette smoking and electronic cigarette use for cessation help

Thus, this may be the first study to suggest that smokers who want to quit smoking for immediate, extrinsic rewards may be attracted to use e-cigarettes to stop smoking cigarettes than smokers who want to quit smoking for intrinsic reasons such as health concerns. In conclusion, e-cigarettes appear to provide a “smoking” alternative to a section of cigarette smokers who may not quit smoking for health reasons. Public health efforts may need to consider employing e-cigarettes to promote tobacco-related harm reduction.

2014: Cigarette Users’ Interest in Using or Switching to Electronic Nicotine Delivery Systems (ENDS) for Smokeless Tobacco for Harm Reduction, Cessation, or Novelty: A Cross-Sectional Survey of US Adults

This study highlights higher interest in ENDS versus smokeless tobacco and greater interest in both for harm reduction and cessation than due to novelty or smoking restrictions. 27.2% of current smokers had talked with a health care provider about ENDS, with 18.0% reporting that their provider endorsed ENDS use for cessation. Developing educational campaigns and informing practitioners about ENDS as cessation or harm reduction aids is critical.

2013: E-Cigarettes: Prevalence and Attitudes in Great Britain

While we found evidence supporting the view that e-cigarette use may be a bridge to quitting, we found very little evidence of e-cigarette use among adults who had never smoked. British smokers would benefit from information about the effective use, risks, and benefits of e-cigarettes, as this might enable the use of e-cigarettes to improve public health.

2013: EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as Tobacco Cigarettes Substitute: A Prospective 12-Month Randomized Control Design Study

Conclusion: “In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.”

2013: 'Vaping' profiles and preferences: an online survey of electronic cigarette users

Seventy-four percent of participants reported not smoking for at least a few weeks since using the e-cigarette and 70% reported reduced urge to smoke. Seventy-two percent of participants used a 'tank' system, most commonly. Mean duration of use was 10 months. Only 1% reported exclusive use of non-nicotine containing liquid. E-cigarettes were generally considered to be satisfying to use; elicit few side effects; be healthier than smoking; improve cough/breathing; and be associated with low levels of craving. Among ex-smokers, 'time to first vape' was significantly longer than 'time to first cigarette' suggesting a lower level of dependence to e-cigarettes. Ex-smokers reported significantly greater reduction in craving than current smokers. E-cigarettes are used primarily for smoking cessation, but for a longer duration than nicotine replacement therapy, and users believe them to be safer than smoking

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.

2011: Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study

Sustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit

2011: Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy

Almost all (97%) used e‐cigarettes containing nicotine. Most (96%) said the e‐cigarette helped them to quit smoking or reduce their smoking (92%). Reasons for using the e‐cigarette included the perception that it was less toxic than tobacco (84%), to deal with craving for tobacco (79%) and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%). Most ex‐smokers (79%) feared they might relapse to smoking if they stopped using the e‐cigarette. Users of nicotine‐containing e‐cigarettes reported better relief of withdrawal and a greater effect on smoking cessation than those using non‐nicotine e‐cigarettes.

2011: Electronic cigarettes (e‐cigs): views of aficionados and clinical/public health Perspectives

The health risks from smoking are large and are known with certainty. Comparatively, the health risks from e‐cig use are likely much smaller (if any) and temporarily switching to e‐cigs will likely yield a large health benefit. If the patient perceives that the e‐cig is helping them to stay off cigarettes and is not reporting any health problems likely attributable to the e‐cig, then the focus should be on staying smoke‐free rather than e‐cig free.

2011: Electronic Cigarettes As a Smoking-Cessation Tool: Results from an Online Survey

A large percentage of respondents reported a reduction in the number of cigarettes they smoked (66.8%) and almost half reported abstinence from smoking for a period of time (48.8%). Those respondents using e-cigarettes more than 20 times per day had a quit rate of 70.0%. Of respondents who were not smoking at 6 months, 34.3% were not using e-cigarettes or any nicotine-containing products at the time.

2011: Interviews With “Vapers”: Implications for Future Research With Electronic Cigarettes

Experienced users report health gains typical for smoking cessation despite continued vaping. There were pervasive themes including the language and culture of vaping; social and informational support among vapers, motives and perceived benefits of using e-cigs versus cigarettes including cigarette-like enjoyment, cost, restored sense of taste and smell, and improved breathing and exercise tolerance; rapidly reduced nicotine tolerance and dependence; and a strong interest in e-cig–related research and policy.

2010: Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial

Conclusions “The 16 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence, was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette. Evaluation of the ENDD for longer-term safety, potential for long-term use and efficacy as a cessation aid is needed.”

2010: Electronic cigarettes: a survey of users

Our results suggest that ecigarettes are used mainly to quit smoking, and may be useful for this purpose.

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

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]

Fluharty et al (2016). The association of cigarette smoking with depression and anxiety: a systematic review. Nicotine & Tobacco Research

• “The literature on the prospective association between smoking and depression and anxiety is inconsistent in terms of the direction of association most strongly supported. This suggests the need for future studies that employ different methodologies, such as Mendelian randomization. . . . Two studies that have used [Mendelian randomization] have found no evidence to support a causal association between smoking and depression and anxiety, while another found evidence to suggest that smoking was associated with lower odds of depression during pregnancy.”

2010 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.