Tobacco

What Is Tobacco?

Tobacco is a tall, sticky-leaved plant of the nightshade family, grown for its leaves, which are rich in the alkaloid nicotine. Nicotiana tabacum is the tobacco of commerce, dried and cured for smoking, chewing and snuff ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}.

It is native to South America and is now cultivated almost worldwide ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}. In North America it replaced Nicotiana rustica as the main cultivated tobacco in the early 1600s ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}.

Nicotine makes up about 90–95% of the leaf’s alkaloids ^{30Reference 30Sun et al. · 2018Variations of alkaloid accumulation and gene transcription in Nicotiana tabacum — plant chemistry (three varieties, five developmental stages)View study →}. Nicotine alone, given by patch or gum, has been tested in trials for ulcerative colitis, mild cognitive impairment and Parkinson’s disease ^{5,8,15Reference 5Newhouse P et al. · 2012RCTNicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial — randomised, placebo-controlled (Class I)View study →Reference 8Sandborn WJ et al. · 1997RCTTransdermal nicotine for mildly to moderately active ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →Reference 15Oertel WH et al. · 2023RCTTransdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trialView study →}.

Nicotiana rustica, called mapacho or Aztec tobacco, is a separate species with more nicotine in its leaf. It is the tobacco of South American ceremony.

How Is Tobacco Used?

• Smoked — as cigarettes, cigars, pipe tobacco and in waterpipes.
• Smokeless — chewed, held in the mouth or taken as snuff, including regional products such as naswar ^{22Reference 22Khan Z et al. · 2017Meta-analysisNaswar (smokeless tobacco) use and the risk of oral cancer in Pakistan — systematic review with meta-analysisView study →}.
• Insecticide — in China the plant is also used to kill insects ^{32Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}.
• Ceremonial — in Indigenous American traditions, though the strong ceremonial preparations mostly use mapacho.

Traditional Uses

Indigenous American Ceremonial Use

In Indigenous American traditions tobacco is a sacred plant. The leaf is used in prayer, in offering and in healing work.

The concentrated ceremonial preparations, such as strong infusions, rapé snuff and tobacco enemas, mostly use mapacho (N. rustica) rather than this species.

Chinese Folk Medicine

In China, where tobacco is widely cultivated, the plant has been used medicinally as an anaesthetic, to induce sweating and to induce vomiting ^{32Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}.

Commercial & Recreational Use

N. tabacum became the principal tobacco of commerce, and it was the mainstay of the economy of the Chesapeake Bay region in colonial times ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}. Its spread as a crop created the everyday use that now defines it: smoked, chewed or snuffed many times a day as a stimulant.

Botany

Tobacco is a soft-wooded herb or shrub in the nightshade family (Solanaceae) ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}, the family of tomato, potato, chilli and datura. It is grown as an annual or lives for a few years, and its single, usually unbranched stem reaches 1–3 m ^{31,32Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}.

The whole plant is covered in sticky glandular hairs ^{31,32Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}. The leaves are large, elliptic to lance-shaped and stalkless, 5–50 cm long and occasionally up to 70 cm. They get smaller towards the top of the stem, and their bases half clasp the stem or run down it as a wing ^{31,32Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}.

The flowers open by day in large branched clusters. Each is a slender tube 3–5 cm long, pale greenish cream to pink or red, opening to a five-pointed face 2–3 cm across in pale to reddish pink or occasionally white ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}. The fruit is an oval capsule 1.2–2 cm long, holding tiny seeds about 0.5 mm across ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}.

The fresh leaf is handled with care. Harvesters who handle wet leaves absorb dissolved nicotine through the skin, which causes green tobacco sickness ^{24Reference 24Centers for Disease Control et al. · 1993ObservationalGreen tobacco sickness in tobacco harvesters — Kentucky, 1992 — observational field reportView study →}.

Distribution

Tobacco is native to South America and is cultivated almost worldwide ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}. It is widely grown throughout China ^{32Reference 32Zhang et al. · 1994Nicotiana tabacum Linnaeus — species description, distribution and uses — floraView study →}.

In North America it occasionally escapes from cultivation, growing as a short-lived weed of disturbed ground and field edges where the climate is mild, from sea level to 1,000 m ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}. Plants left standing at the edges of commercial fields can be mistaken for naturalised weeds ^{31Reference 31KnappKnapp, S. (n.d.). Nicotiana tabacum Linnaeus — species description, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 14 (Solanaceae). http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=200020550View study →}.

Growing Conditions

Cultivation snapshot for Tobacco

• Warmth-loving and frost-tender — grown as a summer annual, needing a long, warm, frost-free season to ripen its leaves.
• Full sun.
• Rich, deep, well-drained soil suits it; the plant is a hungry feeder with a strong taproot.
• Started from the tiny, dust-fine seed sown on the surface and transplanted out once warm.

Grow it yourself

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Phytochemistry

Tobacco leaf contains pyridine alkaloids. In a study of three commercial varieties at five stages of growth, total alkaloids ranged from about 0.6% to 4.2% of leaf dry weight. Nicotine made up about 94% of them, anatabine about 4% and nornicotine under 2%, with anabasine present only in traces ^{30Reference 30Sun et al. · 2018Variations of alkaloid accumulation and gene transcription in Nicotiana tabacum — plant chemistry (three varieties, five developmental stages)View study →}.

Nornicotine is made in the leaf by enzymes that remove a methyl group from nicotine. The mix of its two mirror-image forms varies widely between plants, and this is explained by how selectively those enzymes act ^{1Reference 1Cai B et al. · 2012Enantioselective demethylation of nicotine as a mechanism for variable nornicotine composition in tobacco leafView study →}.

The minor alkaloids have effects of their own. In rodents, nornicotine, anabasine and anatabine each substituted for nicotine in a drug-discrimination test. Only nornicotine was self-administered like nicotine, and all three lowered nicotine self-administration when given beforehand ^{27Reference 27Caine SB et al. · 2014AnimalNicotine-like behavioral effects of the minor tobacco alkaloids nornicotine, anabasine, and anatabine — animal model (rodents)View study →}. Anabasine and anatabine are absent from nicotine-replacement products, so they are used as urine markers of continued tobacco use during nicotine-replacement therapy ^{28Reference 28Jacob P et al. · 2002ObservationalAnabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy — observationalView study →}.

Tobacco smoke also contains the β-carbolines harman and norharman, which are potent, reversible inhibitors of monoamine oxidase (MAO) ^{26Reference 26Herraiz T · 2005In vitroHuman monoamine oxidase is inhibited by tobacco smoke: β-carboline alkaloids act as potent and reversible inhibitors — in vitroView study →}. Together they are estimated to account for less than 10% of the MAO-A inhibition produced by cigarette smoke ^{25Reference 25Hong Y et al. · 2022ReviewA review of monoamine oxidase (MAO) inhibitors in tobacco or tobacco smoke — reviewView study →}.

Constituent Summary

Figures are from the leaves of three Chinese commercial varieties sampled across five stages of growth. Alkaloid content varies widely with variety, leaf position and stage ^{30Reference 30Sun et al. · 2018Variations of alkaloid accumulation and gene transcription in Nicotiana tabacum — plant chemistry (three varieties, five developmental stages)View study →}.

Pharmacology & Research

Research on tobacco falls into two bodies of work. The larger is the epidemiology of harm: cigarettes, cured leaf and smokeless tobacco as causes of cancer, cardiovascular disease and lung disease ^{19,20,21,22,23Reference 19Hackshaw A et al. · 2018Meta-analysisLow cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies — meta-analysis of cohort studiesView study →Reference 20Chang CM et al. · 2021Meta-analysisCigarette smoking reduction and health risks — systematic review and meta-analysisView study →Reference 21Rogers M et al. · 2022Meta-analysisSmokeless tobacco use and waterpipe smoking and the risk of lung cancer — systematic review and meta-analysisView study →Reference 22Khan Z et al. · 2017Meta-analysisNaswar (smokeless tobacco) use and the risk of oral cancer in Pakistan — systematic review with meta-analysisView study →Reference 23Di et al. · 2022Meta-analysisMaternal smoking status during pregnancy and low birth weight in offspring: meta-analysis of 55 cohort studies — meta-analysis of cohort studiesView study →}. The smaller tests the isolated molecule nicotine, given by patch or gum, for possible medical uses.

About ten completed human trials have tested transdermal or nasal nicotine in ulcerative colitis, mild cognitive impairment and Parkinson’s disease. Their results are mixed, and none has led to an approved use ^{5,8,9,10,11,12,15,16Reference 5Newhouse P et al. · 2012RCTNicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial — randomised, placebo-controlled (Class I)View study →Reference 8Sandborn WJ et al. · 1997RCTTransdermal nicotine for mildly to moderately active ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →Reference 9Thomas GA et al. · 1995RCTTransdermal nicotine as maintenance therapy for ulcerative colitis — randomised, double-blind trialView study →Reference 10Thomas GA et al. · 1996RCTTransdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis — randomised, double-blind trialView study →Reference 11Nikfar S et al. · 2010Meta-analysisEfficacy and tolerability of nicotine preparations in active ulcerative colitis — systematic review and meta-analysisView study →Reference 12McGrath J et al. · 2004Systematic reviewTransdermal nicotine for induction of remission in ulcerative colitis — Cochrane systematic reviewView study →Reference 15Oertel WH et al. · 2023RCTTransdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trialView study →Reference 16Villafane G et al. · 2017RCTHigh-dose transdermal nicotine in Parkinson’s disease patients — randomised, open-label, blinded-endpoint phase 2 studyView study →}.

1. Stimulant & Reinforcement

Tobacco’s main activity is the pharmacology of nicotine, and the human evidence for it is extensive. Nicotine is an agonist at nicotinic acetylcholine receptors. Its action in the brain’s reward pathway drives dopamine release, producing arousal, mild euphoria and strong reinforcement, and it makes nicotine one of the most dependence-forming substances in common use ^{2,3,4Reference 2Benowitz NL et al. · 2009ReviewNicotine chemistry, metabolism, kinetics and biomarkers — reviewView study →Reference 3Kim K · 2023ReviewNicotine addiction: more than just dopamine — reviewView study →Reference 4Jasinska AJ et al. · 2013ReviewDual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans — reviewView study →}. Glutamate and GABA signalling in the same system also contribute to nicotine reward ^{3Reference 3Kim K · 2023ReviewNicotine addiction: more than just dopamine — reviewView study →}.

This pharmacology belongs to the molecule and applies equally to N. tabacum and N. rustica.

Dependence is part of the same reward pharmacology, not a separate effect. No medical use exists for tobacco as a stimulant.

2. Cognitive Enhancement

Nicotine’s effect on cognition is the most credible therapeutic signal linked to this plant’s chemistry. In a 6-month double-blind trial in 74 non-smokers with amnestic mild cognitive impairment, 15 mg/day of transdermal nicotine improved the primary attention measure and secondary measures of attention, memory and psychomotor speed ^{5Reference 5Newhouse P et al. · 2012RCTNicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial — randomised, placebo-controlled (Class I)View study →}. It did not change the clinician-rated global impression, and the authors graded it as Class I evidence for improved test performance, not for a clinical benefit ^{5Reference 5Newhouse P et al. · 2012RCTNicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial — randomised, placebo-controlled (Class I)View study →}.

Human brain-imaging studies link nicotine’s effects to cholinergic attention networks ^{4Reference 4Jasinska AJ et al. · 2013ReviewDual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans — reviewView study →}.

In Alzheimer’s disease, a Cochrane review found no trials suitable for inclusion and could not support nicotine as a treatment ^{7Reference 7López-Arrieta JM et al. · 2000Systematic reviewNicotine for Alzheimer’s disease — Cochrane systematic reviewView study →}.

Each of these results used controlled doses of isolated nicotine, not tobacco.

Gap: the evidence is one small, 6-month trial with test-score outcomes; the one clinical measure it used showed no effect, and there is no evidence the plant confers any of this.

3. Ulcerative Colitis

Ulcerative colitis is mainly a disease of non-smokers, and this led to several randomised trials of transdermal nicotine. In mildly to moderately active disease, 12 of 31 patients (39%) on nicotine (11 mg for a week, then up to 22 mg a day) improved at 4 weeks, against 3 of 33 (9%) on placebo ^{8Reference 8Sandborn WJ et al. · 1997RCTTransdermal nicotine for mildly to moderately active ulcerative colitis — randomised, double-blind, placebo-controlled trialView study →}.

Nicotine did not maintain remission better than placebo ^{9Reference 9Thomas GA et al. · 1995RCTTransdermal nicotine as maintenance therapy for ulcerative colitis — randomised, double-blind trialView study →}, and in active disease it was less effective than 15 mg of oral prednisolone and caused more side effects ^{10Reference 10Thomas GA et al. · 1996RCTTransdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis — randomised, double-blind trialView study →}.

The reviews disagree. A 2004 Cochrane review pooled two placebo-controlled trials and found nicotine better than placebo for inducing remission (19 of 71 against 9 of 70), with no advantage over standard treatment and more withdrawals because of side effects ^{12Reference 12McGrath J et al. · 2004Systematic reviewTransdermal nicotine for induction of remission in ulcerative colitis — Cochrane systematic reviewView study →}. A 2010 meta-analysis of three placebo-controlled trials found no significant benefit for remission (relative risk 1.40, 95% CI 0.63–3.12) and more adverse events ^{11Reference 11Nikfar S et al. · 2010Meta-analysisEfficacy and tolerability of nicotine preparations in active ulcerative colitis — systematic review and meta-analysisView study →}.

These trials all used a nicotine patch, not tobacco.

Gap: the benefit, where found, is modest and comes with more side effects, and nicotine is not part of standard ulcerative colitis care.

4. Parkinsonian Neuroprotection

Observational studies consistently find less Parkinson’s disease in smokers. A meta-analysis of 69 studies put the risk in ever-smokers at 0.59 of that in never-smokers (95% CI 0.56–0.62) ^{13Reference 13Li X et al. · 2015Meta-analysisAssociation between cigarette smoking and Parkinson’s disease — meta-analysisView study →}. The association is consistent enough to serve as a “positive control” in studies of Parkinson’s risk factors ^{14Reference 14Breckenridge CB et al. · 2016Meta-analysisAssociation between Parkinson’s disease and cigarette smoking, rural living, well-water consumption, farming and pesticide use — systematic review and meta-analysisView study →}.

In cell and animal models, nicotine acting at α7 nicotinic receptors protects neurons against toxins, including rotenone, which is used to model Parkinson’s disease ^{17,18Reference 17Kumari S et al. · 2025ReviewProposed mechanisms of neuroprotection for nicotine in Parkinson’s disease — reviewView study →Reference 18Shimohama S · 2009AnimalNicotinic receptor-mediated neuroprotection in neurodegenerative disease models — review (animal models)View study →}.

When the treatment was tested directly, it failed. In a double-blind, placebo-controlled trial of 163 people with early, untreated Parkinson’s disease, a year of transdermal nicotine did not slow progression ^{15Reference 15Oertel WH et al. · 2023RCTTransdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trialView study →}. The nicotine group worsened slightly more than placebo on the UPDRS, a difference that fell short of significance on the primary endpoint ^{15Reference 15Oertel WH et al. · 2023RCTTransdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trialView study →}. An earlier open-label study with blinded scoring found no motor benefit at doses up to 90 mg a day ^{16Reference 16Villafane G et al. · 2017RCTHigh-dose transdermal nicotine in Parkinson’s disease patients — randomised, open-label, blinded-endpoint phase 2 studyView study →}.

A 2025 review concluded that neither smoking nor nicotine is recommended to prevent or treat Parkinson’s disease ^{17Reference 17Kumari S et al. · 2025ReviewProposed mechanisms of neuroprotection for nicotine in Parkinson’s disease — reviewView study →}.

Gap: the epidemiology is strong but observational; the one adequately powered interventional trial was negative, so there is no basis for using nicotine — let alone tobacco — to prevent or treat Parkinson’s disease.

Mechanisms

Nicotine is an agonist at nicotinic acetylcholine receptors. Studies have traced its effects in different tissues to this one receptor family: dopamine release in the reward pathway, cholinergic attention signalling, an α7-receptor anti-inflammatory effect in the colon, and nerve protection in animal models.

A separate line of work concerns the β-carbolines harman and norharman in tobacco smoke, which reversibly inhibit monoamine oxidase ^{25,26Reference 25Hong Y et al. · 2022ReviewA review of monoamine oxidase (MAO) inhibitors in tobacco or tobacco smoke — reviewView study →Reference 26Herraiz T · 2005In vitroHuman monoamine oxidase is inhibited by tobacco smoke: β-carboline alkaloids act as potent and reversible inhibitors — in vitroView study →}.

Clinical Trials

The registered therapeutic trials, other than smoking-cessation trials, all test the isolated molecule: small studies of transdermal or nasal nicotine in mild cognitive impairment and Parkinson’s disease, plus the older ulcerative-colitis trials. The main Parkinson’s trial was negative ^{15Reference 15Oertel WH et al. · 2023RCTTransdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trialView study →}.

Last checked: August 2026.

Dosage

Tobacco has no therapeutic dose. Nicotine is a potent poison with a narrow margin between a psychoactive and a toxic amount, and smoking, snuff and oral tobacco are well-documented causes of cancer and cardiovascular disease ^{19,20,21,22Reference 19Hackshaw A et al. · 2018Meta-analysisLow cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies — meta-analysis of cohort studiesView study →Reference 20Chang CM et al. · 2021Meta-analysisCigarette smoking reduction and health risks — systematic review and meta-analysisView study →Reference 21Rogers M et al. · 2022Meta-analysisSmokeless tobacco use and waterpipe smoking and the risk of lung cancer — systematic review and meta-analysisView study →Reference 22Khan Z et al. · 2017Meta-analysisNaswar (smokeless tobacco) use and the risk of oral cancer in Pakistan — systematic review with meta-analysisView study →}.

Ceremonial preparations used in some Indigenous traditions, such as strong infusions, rapé and tobacco enemas, mostly use mapacho. They are far more concentrated than commercial tobacco and have caused fatal poisonings outside their traditional context.

Safety & Pregnancy

Tobacco is highly addictive and toxic. Nicotine is a potent poison, and long-term smoking is a leading cause of cancer and cardiovascular disease.

Full Safety Detail

Acute poisoning. Nicotine is a potent poison. Concentrated preparations or swallowed leaf can cause severe poisoning, with nausea, vomiting, sweating, a racing or irregular heartbeat, seizures and, in extreme cases, death.

Green tobacco sickness. Nicotine dissolved from wet tobacco leaves is absorbed through the skin. In harvesters this causes green tobacco sickness, with nausea, vomiting, weakness, dizziness and sometimes swings in blood pressure or heart rate ^{24Reference 24Centers for Disease Control et al. · 1993ObservationalGreen tobacco sickness in tobacco harvesters — Kentucky, 1992 — observational field reportView study →}. Anyone growing or processing the plant should keep wet leaves off bare skin.

Long-term harm. Smoking, cured-leaf and smokeless use are among the best-established causes of cancer, coronary heart disease, stroke and chronic lung disease. The excess risk is present even at very low daily consumption: one cigarette a day carries about half the excess risk of coronary heart disease and stroke of twenty a day ^{19Reference 19Hackshaw A et al. · 2018Meta-analysisLow cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies — meta-analysis of cohort studiesView study →}. Cutting down lowers lung cancer risk, but the risk stays high, and quitting is the most effective step ^{20Reference 20Chang CM et al. · 2021Meta-analysisCigarette smoking reduction and health risks — systematic review and meta-analysisView study →}.

Smokeless and waterpipe tobacco. Smokeless tobacco and waterpipe smoking both raise the risk of lung cancer ^{21Reference 21Rogers M et al. · 2022Meta-analysisSmokeless tobacco use and waterpipe smoking and the risk of lung cancer — systematic review and meta-analysisView study →}. Naswar, a smokeless tobacco used in Pakistan, is strongly linked to oral cancer ^{22Reference 22Khan Z et al. · 2017Meta-analysisNaswar (smokeless tobacco) use and the risk of oral cancer in Pakistan — systematic review with meta-analysisView study →}.

After a first cancer. Smoking is linked to a higher risk of a second primary cancer in cancer survivors ^{29Reference 29Phua ZJ et al. · 2022Meta-analysisCigarette smoking and risk of second primary cancer — systematic review and meta-analysisView study →}.

Interactions. Nicotine is metabolised mainly by the liver enzyme CYP2A6, and its metabolism is affected by other medications, pregnancy and kidney disease ^{2Reference 2Benowitz NL et al. · 2009ReviewNicotine chemistry, metabolism, kinetics and biomarkers — reviewView study →}.

Tobacco smoke, through its polycyclic aromatic hydrocarbons rather than nicotine, induces the liver enzyme CYP1A2 and speeds the clearance of drugs such as theophylline, caffeine, imipramine, haloperidol and propranolol ^{33Reference 33Zevin S · 1999ReviewDrug interactions with tobacco smokingView study →}. Smokeless tobacco does not appear to do this: in snuff and chewing-tobacco users who did not smoke, theophylline was cleared at the same rate as in non-smokers ^{34Reference 34Parish RC et al. · 1989Clinical pharmacokinetics of theophylline and levels of alpha 1-acid glycoprotein in smokeless tobacco usersView study →}.

References

1. Cai B, Siminszky B, Chappell J, et al. (2012). Enantioselective demethylation of nicotine as a mechanism for variable nornicotine composition in tobacco leaf. J Biol Chem. https://pubmed.ncbi.nlm.nih.gov/23100254/
2. Benowitz NL, Hukkanen J, Jacob P. (2009). Nicotine chemistry, metabolism, kinetics and biomarkers — review. Handbook of Experimental Pharmacology. https://doi.org/10.1007/978-3-540-69248-5_2 https://pubmed.ncbi.nlm.nih.gov/19184645/
3. Kim K, Picciotto MR (2023). Nicotine addiction: more than just dopamine — review. Current Opinion in Neurobiology. https://doi.org/10.1016/j.conb.2023.102797
4. Jasinska AJ, Zorick T, Brody AL, Stein EA. (2013). Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans — review. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2013.02.015
5. Newhouse P, et al. (2012). Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial — randomised, placebo-controlled (Class I). Neurology. https://doi.org/10.1212/WNL.0b013e31823efcbb
6. Fond G, et al. (2015). Innovative mechanisms of action for pharmaceutical cognitive enhancement: a systematic review — systematic review of RCTs. Psychiatry Research. https://doi.org/10.1016/j.psychres.2015.07.006
7. López-Arrieta JM, Rodríguez JL, Sanz F. (2000). Nicotine for Alzheimer’s disease — Cochrane systematic review. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD001749
8. Sandborn WJ, et al. (1997). Transdermal nicotine for mildly to moderately active ulcerative colitis — randomised, double-blind, placebo-controlled trial. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-126-5-199703010-00004
9. Thomas GA, et al. (1995). Transdermal nicotine as maintenance therapy for ulcerative colitis — randomised, double-blind trial. New England Journal of Medicine. https://doi.org/10.1056/NEJM199504133321503
10. Thomas GA, et al. (1996). Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis — randomised, double-blind trial. European Journal of Gastroenterology & Hepatology. https://pubmed.ncbi.nlm.nih.gov/8864674/
11. Nikfar S, et al. (2010). Efficacy and tolerability of nicotine preparations in active ulcerative colitis — systematic review and meta-analysis. Clinical Therapeutics. https://doi.org/10.1016/j.clinthera.2011.01.004
12. McGrath J, McDonald JW, MacDonald JK. (2004). Transdermal nicotine for induction of remission in ulcerative colitis — Cochrane systematic review. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD004722.pub2
13. Li X, et al. (2015). Association between cigarette smoking and Parkinson’s disease — meta-analysis. Archives of Gerontology and Geriatrics. https://doi.org/10.1016/j.archger.2015.08.004
14. Breckenridge CB, et al. (2016). Association between Parkinson’s disease and cigarette smoking, rural living, well-water consumption, farming and pesticide use — systematic review and meta-analysis. PLoS One. https://doi.org/10.1371/journal.pone.0151841
15. Oertel WH, et al. (2023). Transdermal nicotine treatment and progression of early Parkinson’s disease — randomised, double-blind, placebo-controlled trial. NEJM Evidence. https://doi.org/10.1056/EVIDoa2200311
16. Villafane G, et al. (2017). High-dose transdermal nicotine in Parkinson’s disease patients — randomised, open-label, blinded-endpoint phase 2 study. European Journal of Neurology. https://doi.org/10.1111/ene.13474
17. Kumari S, et al. (2025). Proposed mechanisms of neuroprotection for nicotine in Parkinson’s disease — review. Journal of Parkinson’s Disease. https://doi.org/10.1177/1877718X251355112
18. Shimohama S. (2009). Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models — review (animal models). Biological & Pharmaceutical Bulletin. https://doi.org/10.1248/bpb.32.332
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