Nicotine therapeutic benefits: Difference between revisions

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

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

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

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

* Animal study (rat)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

*Lists references

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

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

='''Akathisia'''=

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

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

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

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

='''Alcohol Use Disorder'''=

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

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

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

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

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

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

* Animal study (mice)

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

='''Chlamydia Pneumoniae'''=

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

*See Also: The Inflamation Section

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

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

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

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

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

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

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

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

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

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

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

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

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*Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.

*[https://twitter.com/hbwardMD/status/1487037135299518474 Twitter thread about this study]

*Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).

**Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055

*Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055

***Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).

===2021 [https://academic.oup.com/ntr/article/23/7/1113/6168972 A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes]===

*A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking. Further research with a larger sample and a comparator group is needed.

*[https://academic.oup.com/ntr/article-pdf/23/7/1113/38521536/ntab005.pdf PDF Version]

*Citation: Pasquale Caponnetto, PhD, Jennifer DiPiazza, PhD, Jason Kim, MD, Marilena Maglia, Lyc Psych, Riccardo Polosa, MD, PhD, A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes, Nicotine & Tobacco Research, Volume 23, Issue 7, July 2021, Pages 1113–1122, 10.1093/ntr/ntab005

*Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.

===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0149763420305042?via%3Dihub The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review]===

*Cognitive and early sensory alterations are core features of [https://en.wikipedia.org/wiki/Schizophrenia '''schizophrenia''']. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.

*[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 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.

**Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.

*Keywords: Schizophrenia, Nicotine, Cognition, Early sensory

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

*Animal Study

*“Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.

*Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.

**Citation: Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)

* Ultimately the authors of the study, published in ~~the journal ''Nature Medicine'', envision their work could lead to new non-addictive,~~ nicotine~~-based treatments for some of the 51 million people worldwide who suffer~~ from ~~the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.~~

===2017: [https://pubmed.ncbi.nlm.nih.gov/28441884/ Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging]===

* ~~“Our study provides compelling biological~~ evidence that ~~a specific genetic variant contributes to risk for schizophrenia, defines~~ the ~~mechanism responsible for the effect and validates~~ that nicotine ~~improves that deficit~~,~~” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics~~ (~~IBG~~) ~~and one~~ of ~~four CU Boulder researchers~~ on ~~the study~~.

*This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.

* ~~Note~~: ~~Mouse study; using a model known to mimic human disease~~.

**Citation: Smucny J, Tregellas JR. Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging. J Psychopharmacol. 2017 Jul;31(7):801-811. doi: 10.1177/0269881117705071. Epub 2017 Apr 26. PMID: 28441884; PMCID: PMC5963521.

* Previous genome-wide association studies have suggested that people with a variation in ~~a gene called CHRNA5 are more likely to have~~ schizophrenia~~, but the mechanism for that association has remained unclear. People~~ with ~~that variant are also more likely~~ to ~~smoke~~.

* Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-~~Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio Uwe Maskos Nature Medicine volume 23, pages347–354 (~~2017)

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

*Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.

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

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

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

===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===

*The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.

*[https://sci-hub.st/10.1016/j.mehy.2009.02.017 PDF Version]

*Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

**Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.

===2007: [https://pmc.ncbi.nlm.nih.gov/articles/PMC2702723/ Nicotinic Interactions with Antipsychotic Drugs, Models of Schizophrenia and Impacts on Cognitive Function]===

*Human and Animal study

*Nicotinic receptor systems in the brain are important for a variety of aspects of cognitive function impaired in schizophrenia and aggravated by antipsychotic drugs. Nicotine and selective nicotinic α7 and α4β2 agonists can significantly improve learning, memory and attention. Nicotine and nicotine agonists can reduce some of the cognitive impairments caused by some antipsychotic drugs as well as reduce cognitive impairments seen in the NMDA glutamate blockade animal model of schizophrenia.

**Citation: Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007 Oct 15;74(8):1182-91. doi: 10.1016/j.bcp.2007.07.019. Epub 2007 Jul 20. PMID: 17714691; PMCID: PMC2702723.

***Acknowledgement: Research presented was supported by a grant from the National Institute of Mental Health grant MH64494.

===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===

*For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.

*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

**Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.

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*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

= Stroke =

=== 2025: '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf034/8005730?redirectedFrom=fulltext&login=false The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]''' ===

* Animal study (mice)

* These results demonstrate that nicotine treatment could alleviates the IS-compromised integrity of BBB by regulating the Wnt signal pathway through α7 nAChR.

* The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke.

* Qianqian Pang, Xinyang Yan, Zheng Chen, Liang Yun, Jiang Qian, Zeyi Dong, Miao Wang, Wei Deng, Yao Fu, Tao Hai, Zhichao Chen, Xianfang Rong: Nicotine & Tobacco Research, ntaf034, <nowiki>https://doi.org/10.1093/ntr/ntaf034</nowiki>

='''Tourette's Syndrome'''=

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='''Weight Loss / Appetite Control / Metabolism / Obesity'''=

===2024 Article [https://web.archive.org/web/20241204102835/https://tobaccoreporter.com/2024/12/03/slim-chances/ Harm reduction, smoking cessation and weight]====

*"Nicotine influences eating and weight in multiple ways, from hormones to microbiomes to taste perceptions. The bottom line: Nicotine raises the metabolic rate while also depressing appetite."

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

*Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.

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='''Suggested additions to this page'''=

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

===2024: [https://www.sciencedirect.com/science/article/abs/pii/S0303720724003022?via%3Dihub Nicotine increases hepatocyte transthyretin turnover: a possible mechanism for the protective effect of smoking on preeclampsia?]===

===2011: [https://onlinelibrary.wiley.com/doi/10.1002/hipo.20806 Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat]===

===2017: [https://onlinelibrary.wiley.com/doi/10.1002/brb3.704 Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus]===

===2024: [https://pubmed.ncbi.nlm.nih.gov/39719676/ Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial]===

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

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

~~=== 2014 [http://journals.cambridge.org/abstract_S1834261214000279 Nicotine: Pharmacology, Toxicity and Therapeutic use] ===~~

* Karl Fagerström. Journal of Smoking Cessation, 9, pp 53-59 doi:10.1017/jsc.2014.27

* May need a new heading: general therapeutic use

===2023: [https://drive.google.com/file/d/1ofdbKWq6rIBxI8vQAzjV8z-TYoacrqKB/view Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===

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===2021: [https://pubmed.ncbi.nlm.nih.gov/34757527/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===

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

*Animal

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

*mouse study

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

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

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

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

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

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

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

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

* Powledge TM (2004) Nicotine as Therapy. PLoS Biol 2(11): e404. <nowiki>https://doi.org/10.1371/journal.pbio.0020404</nowiki>

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

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

===~~2021~~: [https://~~link~~.~~springer~~.~~com~~/~~article~~/10.~~1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease~~]===

===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===

===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===

Line 1,579:

Line 1,659:

===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===

===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===

===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===

@@ Line 31: / Line 31: @@
 ='''ADD / ADHD / Attention / Cognition'''=
+=== 2025 '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf060/8078909 Nicotine improves working memory via augmenting BDNF levels through α7 nAChR: evidence from clinical and pre-clinical studies]''' ===
+* While smoking has been associated with many negative consequences to human health, one possible benefit is that nicotine could improve cognitive functions. Previous studies have suggested that smoking may influence brain-derived neurotrophic factor (BDNF) levels.
+* Our research revealed that tobacco product use led to an increase in working memory and human plasma BDNF levels. Furthermore, nicotine was responsible for the elevation in BDNF levels, which showed dose-dependent increases in both serum and the hippocampus, and improved memory performance.
+* Animal study (rat)
+* ''Yingyan Li, PhD, Xin Li, Yaning Fu, PhD, Wenjun Mou, Zuxin Chen, PhD, Ping Wu, PhD, Fanglin Liu, PhD, Huan Chen, PhD, Hongwei Hou, PhD, Qingyuan Hu, PhD: Nicotine & Tobacco Research'', ntaf060, <nowiki>https://doi.org/10.1093/ntr/ntaf060</nowiki>
+===2022 [https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.845646/full Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms]===
+*"Our review of evidence supports the finding that individuals with ADHD are at greater vulnerability for both initiation and continuation of smoking (both cigarettes, e-cigarettes)."
+*"Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes."
+*Taylor, M. R., Carrasco, K., Carrasco, A., & Basu, A. (2022). Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms. Frontiers in Neuroscience, 16, 845646. https://doi.org/10.3389/fnins.2022.845646
+*Funds for open access publication fees are contributed by the Faculty of Health, University of Canterbury and University of Canterbury library.
 ===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
@@ Line 66: / Line 79: @@
 *Citation: Alexandra S. Potter, Paul A. Newhouse, Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder, Pharmacology Biochemistry and Behavior, Volume 88, Issue 4, 2008, Pages 407-417, ISSN 0091-3057, doi: 10.1016/j.pbb.2007.09.014.
 *Acknowledgements: This work was supported by: GCRC M01-00109 and Targacept Inc.
+===2008 [https://pmc.ncbi.nlm.nih.gov/articles/PMC2446482/ Transdermal Nicotine in Adult ADHD With Depression and Anxiety]===
+*"This case report neither rules out the placebo effect, nor does it prove that transdermal nicotine is useful in managing adult ADHD with depression and anxiety. However, it does suggest that the beneficial effect of transdermal nicotine may be attributed to biobehavioral pathways common to chronic nicotine withdrawal and ADHD with depression and anxiety. Nicotine agonists and delivery systems may be new treatments for adult ADHD. Larger well-designed studies are warranted to evaluate the therapeutic potential of nicotine delivery systems in otherwise medically stable adults with ADHD accompanied by depression and anxiety. Further exploration of the nicotinic-cholinergic system may also expand our understanding of the neuropsychiatry underlying ADHD."
+*Citation: Cocores JA. Transdermal nicotine in adult ADHD with depression and anxiety. Prim Care Companion J Clin Psychiatry. 2008;10(3):253-4. doi: 10.4088/pcc.v10n0312f. PMID: 18615164; PMCID: PMC2446482.
+*Dr. Cocores reports no financial affiliations or other relationships relevant to the subject of this letter.
 ===2007 [https://www.academia.edu/2412620/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
@@ Line 82: / Line 100: @@
 *[https://sci-hub.st/https://doi.org/10.1016/j.physbeh.2005.12.011 PDF Version]
 *Citation: D.V. Poltavski, T. Petros, Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits, Physiology & Behavior, Volume 87, Issue 3, 2006, Pages 614-624, ISSN 0031-9384, doi: 10.1016/j.physbeh.2005.12.011.
+===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
+* Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
+* There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
+* People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
+* Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
+*Citation: Powledge TM. Nicotine as therapy. PLoS Biol. 2004 Nov;2(11):e404. doi: 10.1371/journal.pbio.0020404. Epub 2004 Nov 16. PMID: 15547644; PMCID: PMC526783
 ===2003: [https://www.academia.edu/2412608/Is_There_a_Link_Between_Adolescent_Cigarette_Smoking_and_Pharmacotherapy_for_ADHD   Is There a Link Between Adolescent Cigarette Smoking and pharmacotherapy for ADHD?]===
@@ Line 110: / Line 135: @@
 *The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.
 *Citation: Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull. 1996;32(1):67-73. PMID: 8927677.
+===Year Unknown: Article: [https://www.adxs.org/en/page/192/nicotine-as-a-medication-for-adhd Nicotine as a medication for ADHD]===
+*Lists references
 <br>
@@ Line 118: / Line 147: @@
 **Citation: Yang, L., Shen, J., Liu, C. et al. Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org/10.1038/s41467-023-36543-8
 ***Acknowledgement: This work was supported by grants from Shenzhen Science and Technology Program (KQTD20210811090117032), Shenzhen Key Laboratory of Viral Vectors for Biomedicine (ZDSYS20200811142401005), CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024) and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).
+='''Akathisia'''=
+===1997: [https://pubmed.ncbi.nlm.nih.gov/9399378/ Treatment of neuroleptic-induced akathisia with nicotine patches]===
+*We administered 14 mg nicotine patches to 16 patients, all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia.
+*[https://sci-hub.se/10.1007/s002130050436 PDF Version]
+**Citation: Anfang MK, Pope HG Jr. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl). 1997 Nov;134(2):153-6. doi: 10.1007/s002130050436. PMID: 9399378.
+<br>
 ='''Alcohol Use Disorder'''=
@@ Line 400: / Line 437: @@
 * PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
 * Nicotine patches appear to promote blood vessel formation, without adverse effects.
+=== 2015 [https://www.nature.com/articles/srep15895 Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3] ===
+* The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis.
+* The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group.
+* The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
+* Animal study (mice)
+* Ge Li-Sha, Zhao Jing-Lin, Chen Guang-Yi, Liu Li, Zhou De-Pu & Li Yue-Chun ''Scientific Reports'' volume 5, Article number: 15895 (2015)
 ='''Chlamydia Pneumoniae'''=
@@ Line 501: / Line 546: @@
 ='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
 *See Also: The Inflamation Section
+===2025: [https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00167-8 Long COVID – a critical disruption of cholinergic neurotransmission?]===
+*Conclusions: "A review of the literature indicates that a significant disruption of cholinergic neurotransmission might be a central issue for both LC/ME/CFS and PVS. The hypothesis of a viral blockade of nAChRs and the possibility of a competitive reversal of this blockade by LDTN has been corroborated by highly promising results in the broad application of this method to numerous patients. Randomized controlled trials are necessary to determine whether these preliminary results can be substantiated by evidence. However, LDTN application provides many patients with a method that offers a high probability of symptom relief with only minor side effects and represents an affordable therapeutic intervention for the majority of people affected worldwide. Furthermore, dose-finding studies are required to develop individually adapted therapy regimens with regard to dosage and duration of therapy."
+*Citation: Leitzke, M., Roach, D.T., Hesse, S. et al. Long COVID – a critical disruption of cholinergic neurotransmission?. Bioelectron Med 11, 5 (2025). https://doi.org/10.1186/s42234-025-00167-8
 === 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===
@@ Line 703: / Line 752: @@
 **Citation: Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005 Sep 30;67(1-2):161-8. doi: 10.1016/j.brainresbull.2005.06.024. PMID: 16140176.
 <br>
+='''Hashimoto's disease (Hashimoto thyroiditis)'''=
+*[https://www.hopkinsmedicine.org/health/conditions-and-diseases/hashimotos-thyroiditis Hashimoto's Thyroiditis] "is when your thyroid gland becomes irritated or inflamed. Hashimoto thyroiditis is the most common type of this health problem. It may also be called chronic autoimmune thyroiditis. This thyroiditis is an autoimmune disease. It occurs when your body makes antibodies that attack the cells in your thyroid. The thyroid gland becomes overrun with white blood cells and becomes scarred. This makes the gland feel firm and rubbery. The thyroid then can’t make enough of the thyroid hormone."
+===2020: [https://www.endocrine-abstracts.org/ea/0070/ea0070oc8.4?_ga=2.114580999.1434360570.1735281186-102848752.1735281184 Cigarette smoking and the risk to develop symptoms of Hashimoto’s thyroiditis]===
+*"In patients who had discontinued smoking at the age of 39 years or more, the diagnosis of HT was predominantly made after the discontinuation of smoking."
+===2013: [https://onlinelibrary.wiley.com/doi/10.1111/cen.12222 Smoking and thyroid]===
+*"Smoking has distinct associations with thyroid function and size in healthy subjects. It has remarkable and contrasting associations with thyroid function in autoimmune thyroid disease (lower risk of Hashimoto's disease and higher risk of Graves’ disease) and with thyroid size in nodular disease (lower risk of thyroid carcinoma and higher risk of nontoxic goitre and multinodularity). The observed associations likely indicate causal relationships in view of consistent associations across studies, the presence of a dose–response relationship and disappearance of the associations after cessation of smoking. Which mechanisms mediate the many effects of smoking remains largely obscure. Probably, they differ between the various effects. The divergent effects of smoking on the expression of autoimmune thyroid disease are intriguing and reminiscent on the contrasting effects of smoking on inflammatory bowel disease: protective against ulcerative colitis (OR 0·41, 0·34–0·48) but risky for Crohn's disease (OR 1·61, 1·27–2·03)."
 ='''Hypersensitivity Pneumonitis / Extrinsic Allergic Alveolitis''' (See Also: Allergies/Hayfever/Histamines)=
@@ Line 995: / Line 1,053: @@
 *Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
 *[https://twitter.com/hbwardMD/status/1487037135299518474 Twitter thread about this study]
-*Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).
+**Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055
-*Citation: Ward HB, Beermann A, Nawaz U, Halko MA, Janes AC, Moran LV and Brady RO Jr (2022) Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence. Front. Psychiatry 13:804055. doi: 10.3389/fpsyt.2022.804055
+***Acknowledgement: This work was supported by NIMH R01MH116170 (RB); NIMH R01MH111868 and NIMH R01MH117063 (MH); NIDA 1K02DA042987 and NIDA K01DA029645 (AJ); NIMH K23MH110564, NARSAD Young Investigator Award, Brain and Behavior Research Foundation, Pope-Hintz Fellowship Award, McLean Hospital, Dupont-Warren Fellowship Award, and Harvard Medical School (LM); and the Sidney R. Baer, Jr. Foundation, and the Norman E. Zinberg Fellowship in Addiction Psychiatry Research, Harvard Medical School (HW).
-===2021 [https://academic.oup.com/ntr/article/23/7/1113/6168972 A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes]===
-*A high strength nicotine e-cigarette has the potential to help people with schizophrenia spectrum disorders to quit or reduce smoking. Further research with a larger sample and a comparator group is needed.
-*[https://academic.oup.com/ntr/article-pdf/23/7/1113/38521536/ntab005.pdf PDF Version]
-*Citation: Pasquale Caponnetto, PhD, Jennifer DiPiazza, PhD, Jason Kim, MD, Marilena Maglia, Lyc Psych, Riccardo Polosa, MD, PhD, A Single-Arm, Open-Label, Pilot, and Feasibility Study of a High Nicotine Strength E-Cigarette Intervention for Smoking Cessation or Reduction for People With Schizophrenia Spectrum Disorders Who Smoke Cigarettes, Nicotine & Tobacco Research, Volume 23, Issue 7, July 2021, Pages 1113–1122, 10.1093/ntr/ntab005
-*Acknowledgement: The authors wish also to thank PAX Labs (on June 13, 2017 the company became known as JUUL Labs) for the free supplies of JUUL e-cigarette kits and pods. At the time the research was conducted JUUL Labs were not part owned by Altria, a tobacco company. PAX Labs agreed also to supply pods for a further 3 months after the end of the pilot to participants who expressed a wish to continue using as JUUL was not available in Italy when this study has been conducted and not currently available at the 5% nicotine strength.
 ===2020 [https://www.sciencedirect.com/science/article/abs/pii/S0149763420305042?via%3Dihub The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review]===
 *Cognitive and early sensory alterations are core features of [https://en.wikipedia.org/wiki/Schizophrenia '''schizophrenia''']. A single dose of nicotine can improve those features in patients. Attention domain is the most responsive to nicotine in patients. Effects vary upon type of neuropsychological assessment and nicotine intake condition.
 *[https://sci-hub.do/10.1016/j.neubiorev.2020.07.035 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.
+**Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.
-*Keywords: Schizophrenia, Nicotine, Cognition, Early sensory
 === 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===
+*Animal Study
+*“Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
+*Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
+**Citation: Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio  Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)
-* Ultimately the authors of the study, published in the journal ''Nature Medicine'', envision their work could lead to new non-addictive, nicotine-based treatments for some of the 51 million people worldwide who suffer from the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.
+===2017: [https://pubmed.ncbi.nlm.nih.gov/28441884/ Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging]===
-* “Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
+*This brief review discusses evidence from neurophysiological and neuroimaging studies in schizophrenia patients that nicotinic agonists may effectively target dysfunctional neuronal circuits in the illness. Evidence suggests that nicotine significantly modulates a number of these circuits, although relatively few studies have used modern neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to examine the effects of nicotinic drugs on disease-related neurobiology. The neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain a priority for psychiatry research.
-* Note: Mouse study; using a model known to mimic human disease.
+**Citation: Smucny J, Tregellas JR. Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging. J Psychopharmacol. 2017 Jul;31(7):801-811. doi: 10.1177/0269881117705071. Epub 2017 Apr 26. PMID: 28441884; PMCID: PMC5963521.
-* Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
-* Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio  Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)
 ===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
 *Nicotine is used for a number of reasons. In human studies, acute administration of nicotine can have positive effects on cognitive processes, such as improving attention, fine motor coordination, concentration, memory, speed of information processing, and alleviation of boredom or drowsiness. Some nicotine users benefit from self-medication effects for alleviation of stress, anxiety, depression, and other mental health and medical conditions, including schizophrenia and Parkinson’s Disease. Nicotine also reverses cognitive deficits caused by withdrawal. It is not clear if chronic use of nicotine enhances cognitive function.
 *Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
-*Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner
+**Citation: Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner
 ===2009 [https://pubmed.ncbi.nlm.nih.gov/19328631/ Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications]===
 *The principal reason for the markedly increased rate of cigarette smoking in people with schizophrenia: tobacco cigarette smoking represents an attempt at self-medication in schizophrenia, because the additional nicotine so provided alleviates the hypofunctional sensory gating seen in this illness.
 *[https://sci-hub.st/10.1016/j.mehy.2009.02.017 PDF Version]
-*Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.
+**Citation: Conway JL. Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. 2009 Aug;73(2):259-62. doi: 10.1016/j.mehy.2009.02.017. Epub 2009 Mar 27. PMID: 19328631.
+===2007: [https://pmc.ncbi.nlm.nih.gov/articles/PMC2702723/ Nicotinic Interactions with Antipsychotic Drugs, Models of Schizophrenia and Impacts on Cognitive Function]===
+*Human and Animal study
+*Nicotinic receptor systems in the brain are important for a variety of aspects of cognitive function impaired in schizophrenia and aggravated by antipsychotic drugs. Nicotine and selective nicotinic α7 and α4β2 agonists can significantly improve learning, memory and attention. Nicotine and nicotine agonists can reduce some of the cognitive impairments caused by some antipsychotic drugs as well as reduce cognitive impairments seen in the NMDA glutamate blockade animal model of schizophrenia.
+**Citation: Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007 Oct 15;74(8):1182-91. doi: 10.1016/j.bcp.2007.07.019. Epub 2007 Jul 20. PMID: 17714691; PMCID: PMC2702723.
+***Acknowledgement: Research presented was supported by a grant from the National Institute of Mental Health grant MH64494.
 ===2002 [https://pubmed.ncbi.nlm.nih.gov/12769614/ Nicotinic treatment for cognitive dysfunction]===
 *For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer's disease, schizophrenia or ADHD as well as normal nonsmoking adults.
-*Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.
+**Citation: Levin ED, Rezvani AH. Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):423-31. doi: 10.2174/1568007023339102. PMID: 12769614.
 <br>
@@ Line 1,436: / Line 1,495: @@
 *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
-<br>
+= Stroke =
+=== 2025: '''[https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf034/8005730?redirectedFrom=fulltext&login=false The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]''' ===
+* Animal study (mice)
+* These results demonstrate that nicotine treatment could alleviates the IS-compromised integrity of BBB by regulating the Wnt signal pathway through α7 nAChR.
+* The study demonstrates that nicotine at low concentrations exerts neuro-protective effects by supporting the integrity of BBB and subsequent endothelial viability after ischemic stroke.
+* Qianqian Pang, Xinyang Yan, Zheng Chen, Liang Yun, Jiang Qian, Zeyi Dong, Miao Wang, Wei Deng, Yao Fu, Tao Hai, Zhichao Chen, Xianfang Rong: Nicotine & Tobacco Research, ntaf034, <nowiki>https://doi.org/10.1093/ntr/ntaf034</nowiki>
 ='''Tourette's Syndrome'''=
@@ Line 1,499: / Line 1,566: @@
 ='''Weight Loss / Appetite Control / Metabolism / Obesity'''=
+===2024 Article [https://web.archive.org/web/20241204102835/https://tobaccoreporter.com/2024/12/03/slim-chances/ Harm reduction, smoking cessation and weight]====
+*"Nicotine influences eating and weight in multiple ways, from hormones to microbiomes to taste perceptions. The bottom line: Nicotine raises the metabolic rate while also depressing appetite."
 ===2011 [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-129 Anti-inflammatory effects of nicotine in obesity and ulcerative colitis]===
 *Nicotine, the principal addictive constituent of tobacco, has been shown to suppress appetite and attenuates obesity in many studies, but the underlying mechanism is not clear.
@@ Line 1,515: / Line 1,585: @@
 ='''Suggested additions to this page'''=
+===2025: [https://pubmed.ncbi.nlm.nih.gov/39921606/ The protective effect of low-dose nicotine on ischemia stroke by maintaining the integrity of the blood-brain barrier]===
+===2024: [https://www.sciencedirect.com/science/article/abs/pii/S0303720724003022?via%3Dihub Nicotine increases hepatocyte transthyretin turnover: a possible mechanism for the protective effect of smoking on preeclampsia?]===
+===2011: [https://onlinelibrary.wiley.com/doi/10.1002/hipo.20806 Acute nicotine treatment prevents rem sleep deprivation-induced learning and memory impairment in rat]===
+===2017: [https://onlinelibrary.wiley.com/doi/10.1002/brb3.704 Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus]===
+===2024: [https://pubmed.ncbi.nlm.nih.gov/39719676/ Effect of Nicotine Replacement Therapy on Perioperative Pain Management and Opioid Requirement in Abstinent Tobacco Smokers Undergoing Spinal Fusion: A Double-blind Randomized Controlled Trial]===
+===2012: [https://pmc.ncbi.nlm.nih.gov/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
 ===2024: [https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1427314/full The double-edged nature of nicotine: toxicities and therapeutic potentials]===
-=== 2014 [http://journals.cambridge.org/abstract_S1834261214000279 Nicotine: Pharmacology, Toxicity and Therapeutic use] ===
-* Karl Fagerström. Journal of Smoking Cessation, 9, pp 53-59 doi:10.1017/jsc.2014.27
-* May need a new heading: general therapeutic use
 ===2023: [https://drive.google.com/file/d/1ofdbKWq6rIBxI8vQAzjV8z-TYoacrqKB/view Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders]===
@@ Line 1,548: / Line 1,626: @@
 ===2021: [https://pubmed.ncbi.nlm.nih.gov/34757527/ Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia]===
 ===2012: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286320/ Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats]===
 *Animal
 ===2021: [https://www.sciencedirect.com/science/article/abs/pii/S1001841721007804 Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS]===
 *mouse study
 ===2021: [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006219.pub4/full Interventions for preventing weight gain after smoking cessation]===
+*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
+===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
-*There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
+* Yet few of the horrendous health effects of smoking are traceable to nicotine itself—cigarettes contain nearly 4,000 other compounds that play a role. Until recently, nicotine research has been driven primarily by nicotine's unparalleled power to keep people smoking, rather than its potential therapeutic uses.
+* There's a cheap, common, and mostly safe drug, in daily use for centuries by hundreds of millions of people, that only lately has been investigated for its therapeutic potential for a long list of common ills. The list includes Alzheimer disease, Parkinson disease, depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), and even pain and obesity.
+* People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli and screen out the rest. Nicotine helps.
+* Researchers at the National Institute on Drug Abuse have shown via functional magnetic resonance imaging that nicotine activates specific brain areas during tasks that demand attention
+* Powledge TM (2004) Nicotine as Therapy. PLoS Biol 2(11): e404. <nowiki>https://doi.org/10.1371/journal.pbio.0020404</nowiki>
-===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
+===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===
-===2021: [https://link.springer.com/article/10.1007/s12640-021-00375-5 Novel Pharmacotherapies in Parkinson’s Disease]===
+===2001: [https://today.duke.edu/2001/08/mm_medicaluses.html Medical Uses for Nicotine]===
 ===2021: [https://pubmed.ncbi.nlm.nih.gov/33675460/ Nicotine gum enhances visual processing in healthy nonsmokers]===
@@ Line 1,579: / Line 1,659: @@
 ===1986: [https://pubmed.ncbi.nlm.nih.gov/3786334/ Effects of nicotine on finger tapping rate in non-smokers]===
+===1996: [https://sci-hub.st/10.1093/oxfordjournals.bmb.a011533 Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious]===
 ===2020 [https://n.neurology.org/content/neurology/94/20/e2132.full.pdf Tobacco smoking and the risk of Parkinson disease A 65-year follow-up of 30,000 male British doctors]===