Nicotine therapeutic benefits: Difference between revisions

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* Animal study (rat)

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

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

*Review includes human and animal studies.

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

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

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

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

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

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

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*Citation: Gehricke, J.-G., Loughlin, S., Whalen, C., Potkin, S., Fallon, J., Jamner, L., … Leslie, F. (2007). Smoking to self-medicate attentional and emotional dysfunctions. Nicotine Tobacco Research, 9, 523–536. https://doi.org/10.1080/14622200701685039

===2007: [https://~~www~~.~~academia~~.~~edu~~/~~18995031~~/~~Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self~~-~~medicate attentional and emotional dysfunctions~~]===

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

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

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

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

***Acknowledgement: Paywalled, unable to access.

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

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===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.

*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.

*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.

*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

*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

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

***Acknowledgement: None stated

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

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

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

*Review includes human and animal studies.

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

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

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

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

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

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

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

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

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

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

*Animal Study

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

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

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

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

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

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

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

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

***Acknowledgement: None stated

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

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*[https://sci-hub.st/10.1192/bjp.154.6.797 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.

='''Antimicrobial Agent'''=

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

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

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

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==Osteoarthritis==

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

*Review includes human and animal studies.

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

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

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

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

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

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

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

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

*Review includes human and animal studies.

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

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

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

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

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

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

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

= '''~~Atopic Dermatitis~~''' =

='''Ataxia'''=

=== ~~2023~~: [https://~~pubmed~~.ncbi.nlm.nih.gov/~~37454697~~/ ~~Association of Atopic Dermatitis with Substance Use~~ Disorders~~: A Case-Control Study in the All of Us Research Program.~~] ===

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

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

* ~~Joshi TP~~, ~~Bancroft A~~, ~~DeLeon D~~, ~~Garcia D~~, ~~Kunisetty B~~, ~~Truong P, Kim SJ. J Am Acad Dermatol. 2023 Jul 14:S0190-9622(23)01361-0. doi: 10~~.~~1016~~/~~j.jaad.2023.06.051. Online ahead of print. PMID: 37454697 No abstract available~~.

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

* ~~Patients with AD~~, ~~compared to controls~~, ~~were more likely to use cannabis (4.4% vs 2.7%~~, ~~60 P <0~~.~~01), hallucinogens (3~~.~~2% vs 1~~.~~8%, P <0.01), opioids~~ (3~~.5% vs 1.3%, P <0.01~~)~~, and 61 stimulants (2~~.~~3% vs 1.5%, P <0.01) and less likely to use e-cigarettes (~~10.~~8% vs 15~~.~~6%, P <0.01) 62 and regular cigarettes (39.0% vs 56.0%, P <0.01)~~.

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

* ~~In multivariable analysis adjusted for age, 63 income, insurance type, race, sex, depression, and anxiety, only~~ the ~~associations with cannabis 64 (aOR 1~~.~~49, 95% CI 1.24-1.80), e-cigarette (aOR 0.71, 95% CI 0.65-0.77), and regular cigarette 65 use (aOR 0.65, 95% CI 0.63-0.68) persisted (Table I)~~

= '''Auditory''' =

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**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).

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

*Animal Study

*

**Citation:

***Acknowledgement:

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

*Animal Study

*

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

**Citation:

***Acknowledgement:

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

*Animal Study

*

**Citation:

***Acknowledgement:

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

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

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

*Review includes human and animal studies.

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

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

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

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

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

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

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

*See also: Sleep - REM

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

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

* Author: Ahmad Alhowail

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

*Animal study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

*Animal Study

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

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

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

***Acknowledgement: None stated

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

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

***Paywalled, unable to view funding/COI

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

*Review includes human and animal studies.

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

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

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

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

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

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

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='''Dyskinesia'''=

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

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

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

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

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

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

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

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

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

='''Dystonia'''=

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

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

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

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

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**Citation: Thomson K, Karouta C, Ashby R. Administration of Nicotine Can Inhibit Myopic Growth in Animal Models. Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):29. doi: 10.1167/iovs.65.11.29. PMID: 39292451; PMCID: PMC11412605.

***Acknowledgement: Funded by ANU Connect Ventures through a Discovery Translation Fund grant (Project ID: DTF311).

~~ ~~

~~='''Huntington’s Disease'''=~~

~~===2005: [https://pubmed.ncbi.nlm.nih.gov/16140176/ Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats]===~~

*These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.

*In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.

*[https://sci-hub.se/10.1016/j.brainresbull.2005.06.024 PDF Version]

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

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

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

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

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

***Acknowledgement: None stated

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

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

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

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

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

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

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

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

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

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

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

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

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

='''Huntington’s Disease'''=

===2005: [https://pubmed.ncbi.nlm.nih.gov/16140176/ Neuroprotective effect of nicotine against 3-nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats]===

*These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.

*In conclusion, nicotine significantly and dose-dependently attenuated 3-NP-induced striatal lesions and behavioral deficits in rats. The protective effect of nicotine may be attributed to its ability of restoring striatal DA levels in 3-NP intoxicated rats.

*[https://sci-hub.se/10.1016/j.brainresbull.2005.06.024 PDF Version]

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

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

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

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

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

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

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

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

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

='''Hypothyroidism'''=

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

*Animal Study

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

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

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

***Acknowledgement: None stated

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

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

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

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

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

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

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

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

***Acknowledgement: None stated

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

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

*Review includes human and animal studies.

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

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

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

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

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

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

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

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