Nicotine
Nicotine is a naturally occurring alkaloid found primarily in tobacco and in trace amounts in plants such as tomatoes and aubergines.1 It acts as a stimulant at low doses, promoting the release of dopamine, serotonin, and adrenaline,2 while higher doses produce calming and muscle-relaxing effects. Widely regarded as one of the most addictive substances known,3 it is used both recreationally through tobacco products and therapeutically as a smoking cessation aid.4
Contents
Dosage & Duration
Dosage
An average cigarette delivers approximately 2 mg of absorbed nicotine, a reinforcing dose that remains far below toxic levels.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Nicotine acts as an agonist at most subtypes of nicotinic acetylcholine receptors (nAChRs), with particularly high affinity at the α4β2 subtype (Ki = 1 nM)5, while functioning as an antagonist at the α9 and α10 subtypes.5 Activation of central nAChRs stimulates the release of multiple neurotransmitters including dopamine, norepinephrine, acetylcholine, and serotonin.6 Binding at α4β2 receptors on dopaminergic neurons within the mesolimbic pathway drives dopamine release, which underlies the substance's reinforcing properties.7 Nicotine also acts on nicotinic receptors in the adrenal medulla, triggering the release of epinephrine and norepinephrine into the bloodstream through calcium-dependent exocytosis. The naturally occurring (S)-enantiomer is 4 to 28 times more potent than (R)-nicotine in standard binding and functional assays.5
Pharmacokinetics
Nicotine distributes rapidly through the bloodstream and crosses the blood-brain barrier within 10 to 20 seconds of inhalation.1 It is primarily metabolized in the liver by CYP2A6, with additional contributions from CYP2B6 and FMO3 (the latter selectively metabolizing the (S)-enantiomer).1 The major metabolite is cotinine, which is pharmacologically active and persists in the blood with a half-life of 15 to 20 hours.8 Nicotine itself has an elimination half-life of approximately 1 to 3 hours.1 Absorption is modulated by the molecule's ionization state, which is governed by pH relative to its pKa values.1
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Other nicotinic acetylcholine receptor agonists
Harm Potential
Addiction & Dependence
Psychological
Extremely HighNicotine is consistently described as one of the most addictive drugs in existence.9 It activates the mesolimbic reward pathway and induces long-term ΔFosB expression in the nucleus accumbens, resulting in strong psychological dependence. Discontinuation produces affective withdrawal symptoms including anxiety, irritability, intense craving, and anhedonia.10
Physical
HighNicotine produces significant physical dependence with chronic use. Withdrawal symptoms include somatic effects such as mild motor dysfunction and tremor, alongside depression, restlessness, insomnia, and in the long-term with abstinence, weight gain.10 Withdrawal symptoms peak within one to three days and can persist for several weeks, though withdrawal is not life-threatening.10
Toxicity
Acute use causes transient increases in heart rate, blood pressure, and systemic vasoconstriction including coronary arteries;11 long-term exposure may impair endothelial function and potentially contribute to atherosclerosis, with cardiac arrhythmias primarily a concern in individuals with underlying heart disease. Short-term nicotine use in healthy individuals poses little cardiovascular risk.11
Heavy chronic use is associated with less efficient brain network architecture and disruptions in topological organization of brain networks; adolescent exposure may impair neurodevelopment up to age twenty-five,13 and some research suggests potential damage to medial habenula neurons regulating nicotine avoidance behaviors in chronic users.
Nicotine is considered a possible teratogen in humans; it crosses the placenta and negatively affects fetal brain development, with prenatal exposure associated with lower birth weight, increased risk of miscarriage and stillbirth, and potential long-term metabolic and neurobehavioral consequences in offspring.14
Chronic exposure suppresses both innate and adaptive immune responses, downregulating cell-mediated immunity against infections and potentially reducing immune surveillance against neoplastic diseases.15
May promote and aggravate periodontal diseases including periodontitis and gingivitis, particularly in the presence of harmful oral microorganisms.
Seizure Risk
Seizures are documented only at toxic or overdose-level doses and do not occur at typical recreational or therapeutic doses. Lethal nicotine poisoning rapidly produces seizures, and death from respiratory paralysis may occur within minutes of a severe overdose.17
History & Culture
Introduction to Europe
Tobacco first arrived in Europe during the early 1530s, brought back by Spanish explorers from the Americas. The plant quickly gained a reputation as a medicinal wonder, with smoking believed to offer protection against various illnesses, including the plague. This perception of tobacco as a "holy…
Legality
By Country
Arizona
California
District of Columbia
Guam
Illinois
Iowa
Maine
Massachusetts
Minnesota
Nebraska
New Hampshire
New York
North Carolina
Northern Mariana Islands
Ohio
Puerto Rico
Rhode Island
South Dakota
Utah
Virginia
Washington
References
Source Pages
Citations
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- Stratton K, Shetty P, & Wallace R. (2001). Nicotine Pharmacology. Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction. https://www.ncbi.nlm.nih.gov/books/NBK222359/1
- Aslam SP, Leslie SW, & Morris J. (2024). Nicotine Addiction and Smoking: Health Effects and Interventions. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK537066/1
- (December 2014). Nicotine: Pharmacology, Toxicity and Therapeutic use. Journal of Smoking Cessation, 9(2), 53–59. https://doi.org/10.1017/jsc.2014.271
- (n.d.). Nicotine: Biological activity. IUPHAR/BPS Guide to Pharmacology. https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=25851234
- (July 2010). Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology, 210(4), 453–469. https://doi.org/10.1007/s00213-010-1848-11
- (May 2018). Cognitive Effects of Nicotine: Recent Progress. Current Neuropharmacology, 16(4), 403–414. https://doi.org/10.2174/1570159x156661711031521361
- (1988). Elimination of cotinine from body fluids: Implications for noninvasive measurement of tobacco smoke exposure. American Journal of Public Health, 78(6), 696–698. https://doi.org/10.2105/ajph.78.6.6961
- (January 1995). The scientific case that nicotine is addictive. Psychopharmacology, 117(1), 2–10; discussion 14–20. https://doi.org/10.1007/bf022450881
- (2015). The Neuropharmacology of Nicotine Dependence. 24, 99–123. https://doi.org/10.1007/978-3-319-13482-6_4123
- Benowitz NL, & Gourlay SG. (1997). Cardiovascular Toxicity of Nicotine: Implications for Nicotine Replacement Therapy. Journal of the American College of Cardiology, 29(7), 1422–1431. https://doi.org/10.1016/s0735-1097(97)00079-x12
- Mills EJ, Wu P, Lockhart I, Wilson K, & Ebbert JO. (2010). Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tobacco Induced Diseases, 8(1), 8. https://pmc.ncbi.nlm.nih.gov/articles/PMC2917405/1
- (2025-01-31). Health Effects of Vaping. Smoking and Tobacco Use. https://www.cdc.gov/tobacco/e-cigarettes/health-effects.html1
- (August 2010). Long-term consequences of fetal and neonatal nicotine exposure: a critical review. Toxicological Sciences, 116(2), 364–374. https://doi.org/10.1093/toxsci/kfq103123
- (2023). Effect of Nicotine on Immune System Function. Biomolecules. https://pmc.ncbi.nlm.nih.gov/articles/PMC9871277/1234
- (2015). Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review. Frontiers in Oncology, 5, 196. https://doi.org/10.3389/fonc.2015.00196123
- (January 2014). How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Archives of Toxicology, 88(1), 5–7. https://doi.org/10.1007/s00204-013-1127-01
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- (n.d.). John Rolfe. World History Encyclopedia. https://www.worldhistory.org/John_Rolfe/1
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- McIndoo NE. (1943). Insecticidal Uses of Nicotine and Tobacco: A Condensed Summary of the Literature, 1690-1934. United States Department of Agriculture, Bureau of Entomology and Plant Quarantine. https://archive.org/stream/idaluses00unit/idaluses00unit_djvu.txt1
- Tinkler P. (2019). Superman vs. Nick O'Teen: anti-smoking campaigns and children in 1980s Britain. Humanities and Social Sciences Communications, 5. https://doi.org/10.1057/s41599-019-0326-612
- (n.d.). Ministry of Health Resolution No. 549/2026. argentina.gob.ar. https://www.argentina.gob.ar/normativa/nacional/resoluci%C3%B3n-549-2026-425443/texto1
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- (n.d.). Tobacco and Vaping Products Act (S.C. 1997, c. 13); Nicotine Concentration in Vaping Products Regulations (SOR/2021-123). laws-lois.justice.gc.ca. https://laws-lois.justice.gc.ca/eng/acts/T-11.5/FullText.html1
- (n.d.). Tobacco and Vaping Products Act (S.C. 1997, c. 13); Nicotine Concentration in Vaping Products Regulations (SOR/2021-123). laws-lois.justice.gc.ca. https://laws-lois.justice.gc.ca/eng/regulations/SOR-2021-123/FullText.html1
- (n.d.). Tobacco and Vaping Products Act (S.C. 1997, c. 13); Nicotine Concentration in Vaping Products Regulations (SOR/2021-123). canada.ca. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/revisions-nicotine-buccal-pouches.html1
- (n.d.). Law No. 2354 of 2024. secretariasenado.gov.co. https://www.secretariasenado.gov.co/senado/basedoc/ley_2354_2024.html1
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- (n.d.). Tabaks- en rookwarenwet. wetten.overheid.nl. https://wetten.overheid.nl/BWBR0037160/2025-07-01/01
- (n.d.). Republic Act No. 11900. elibrary.judiciary.gov.ph. https://elibrary.judiciary.gov.ph/thebookshelf/showdocs/2/956211
- (n.d.). Lei n.º 37/2007. info.portaldasfinancas.gov.pt. https://info.portaldasfinancas.gov.pt/pt/informacao_fiscal/legislacao/diplomas_legislativos/Documents/Lei_37_2007.pdf1
- (n.d.). Tobacco Business Act. law.go.kr. https://www.law.go.kr/LSW/lsInfoP.do?lsId=0005831
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- (n.d.). Real Decreto 579/2017. boe.es. https://www.boe.es/buscar/act.php?id=BOE-A-2017-65851
- (n.d.). Law No. 2899-IV on Measures to Prevent and Reduce the Use of Tobacco Products and Their Harmful Effects on Public Health. zakon.rada.gov.ua. https://zakon.rada.gov.ua/laws/show/2899-15#Text1
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- (n.d.). Cal. Health & Safety Code § 104559.5. leginfo.legislature.ca.gov. https://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?bill_id=201920200SB7931
- (n.d.). Cal. Health & Safety Code § 104559.5. oag.ca.gov. https://oag.ca.gov/tobacco/flavorban/regulations1
- (n.d.). D.C. Code §§ 7-1721.01 and 7-1721.08. code.dccouncil.gov. https://code.dccouncil.gov/us/dc/council/code/sections/7-1721.011
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- (n.d.). 10 GCA § 90A102. col.guamcourts.gov. https://col.guamcourts.gov/sites/default/files/10gc090A.pdf1
- (n.d.). 35 ILCS 143/10-5; 410 ILCS 86/15. ilga.gov. https://www.ilga.gov/legislation/ILCS/details?ActID=588&ActName=Tobacco+Products+Tax+Act+of+1995.&ChapAct=35+ILCS+143%2F&Chapter=REVENUE&ChapterID=8&MajorTopic=GOVERNMENT&SeqEnd=3600000&SeqStart=18000001
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Further Reading
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