Nicotine

3-[(2S)-1-methylpyrrolidin-2-yl]pyridine

Overview

Nicotine belongs to Stimulants.

Key safety note: Nicotine is strongly dependence-forming, one of the most addictive drugs in common use, through fast delivery to the brain and mesolimbic dopamine release.[4][6]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • A quick, mild lift: increased alertness, concentration and arousal, a faster heart rate, and appetite suppression: often experienced as relaxing, especially in dependent users for whom it relieves craving.
  • Physical effects: raised heart rate and blood pressure, and, with inhaled forms, airway irritation. Nausea, dizziness and a 'head rush' in naïve users or at higher doses.
  • The reward is brief and quickly followed by wanting more. Withdrawal on stopping brings irritability, anxiety, restlessness, poor concentration, increased appetite and strong craving.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Inhaled (smoked/vaped), oral/buccal (snus, gum, lozenge), transdermal (patch) or nasal. Nicotine is not dosed in discrete 'recreational tiers': the figures below are context, not a recommendation.. Nicotine delivery depends heavily on the product and how it is used. A cigarette contains roughly 10–15 mg of nicotine but delivers only about 1–2 mg to the smoker. NRT products are labelled by nicotine content (e.g. patches ~7–21 mg/24 h, gum 2–4 mg per piece). E-liquid strength varies enormously (from a few mg/mL to very high 'nic-salt' concentrations). Pure nicotine and concentrated e-liquid are acutely toxic if swallowed and must be kept away from children and pets. There is no safe way to use it that avoids its high dependence potential. If used, prefer non-combusted forms and the lowest strength that controls craving.

Dose ranges

Per cigarette (delivered)

≈1–2 mg absorbed (of ~10–15 mg content)

NRT gum/lozenge

2–4 mg per piece

NRT patch

≈7–21 mg over 24 h

Duration

Chemical & Physical Properties
FormulaC10H14N2
Molar mass162.23 g/mol
StateLiquid
Melting point-79 °C
Boiling point247 °C
Density1.0097 g/cm³ at 20 °C (EPA, 1998)
Vapor pressure1 mmHg at 62 °C (EPA, 1998)
pKa8.11
LogP1.17
SolubilityMiscible (NTP, 1992), 1000000 mg/L, Miscible with water below 60 °C. Very sol in alcohol, chloroform, ether, petroleum ether, kerosene, oils
Refractive index1.5282 at 20 °C (D line)
Identifiers & Synonyms
CAS54-11-5
CAS (enantiomer)
PubChem CID89594
InChIKeySNICXCGAKADSCV-JTQLQIEISA-N
InChIInChI=1S/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
SMILESCN1CCC[C@H]1c1cccnc1

Synonyms

  • (S)-Nicotine
  • 3-(1-methylpyrrolidin-2-yl)pyridine
  • Nicotine
Pharmacodynamics & Biochemistry

Nicotine is the principal psychoactive alkaloid of tobacco (Nicotiana) and an agonist at nicotinic acetylcholine receptors (nAChRs): ligand-gated cation channels. Its high-affinity central target is the α4β2 subtype (Kᵢ in the low-nanomolar range), with additional activity at the α7 subtype (low affinity, rapidly desensitising) and at ganglionic α3β4 and neuromuscular receptors. Opening these channels depolarises neurons and, importantly, drives dopamine release in the mesolimbic reward pathway: the basis of nicotine's reinforcing, dependence-forming effect. The subjective effect is biphasic and situational: nicotine is a mild stimulant (increased alertness, concentration and heart rate, appetite suppression) but is also experienced as relaxing, partly because it relieves the withdrawal of dependent users. nAChRs desensitise quickly and then up-regulate with repeated exposure, which underlies rapid tolerance and the craving–withdrawal cycle. Peripheral actions include activation of the airway irritant receptor TRPA1 (contributing to the harshness of inhaled nicotine) and sympathetic/ganglionic stimulation. It is a weak base absorbed rapidly across the lungs (and buccal/nasal mucosa at suitable pH), reaching the brain within seconds of inhalation: the fast delivery that makes smoking and vaping so addictive. It is metabolised in the liver mainly by CYP2A6 to cotinine (itself long-lived, t½ ≈16 h, and used as an exposure biomarker). The nicotine plasma half-life is only ~1–2 h, which drives frequent redosing through the day.

Biological targets

  • nAChR

Binding & functional measurements

TargetMeasurementSpecies
nicotinic acetylcholine receptor α4 subunitpKi 8.7Human
nicotinic acetylcholine receptor α3 subunitpKi 5.8Human
Pharmacokinetics
BioavailabilityInhaled ≈80–90%, oral low (first-pass)
TmaxSmoked ≈minutes, gum/patch slower
Half-life≈1–2 h (metabolite cotinine ≈16 h)
VdNot reported
Protein bindingNot reported
MetabolismHepatic CYP2A6 to cotinine
ExcretionRenal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Nicotine is strongly dependence-forming, one of the most addictive drugs in common use, through fast delivery to the brain and mesolimbic dopamine release. Most people who use it regularly find it hard to stop. It raises heart rate and blood pressure and constricts blood vessels, so it stresses the cardiovascular system (caution after a recent heart attack, in unstable angina, uncontrolled hypertension or serious arrhythmia). It is genuinely toxic in overdose: concentrated e-liquids and pure nicotine can cause acute poisoning (nausea, vomiting, salivation, sweating, tremor, seizures and, at high doses, respiratory failure), which is a real hazard for children and pets who swallow refill liquid: such products must be stored safely. In pregnancy it harms fetal development. Two important caveats, though: the great majority of tobacco-related death and disease comes from the combustion products of smoking, NOT from nicotine itself, and nicotine is not a meaningful cause of cancer, and nicotine-replacement therapy is an established, comparatively safe way to deliver it for quitting. Youth use of high-strength vapes is a particular dependence concern.[4][6]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

CYP1A2 substrate drugs (clozapine, olanzapine, theophylline) Tobacco smoke (not nicotine itself) induces CYP1A2, lowering levels of clozapine, olanzapine, theophylline and caffeine. Stopping smoking can raise those levels, sometimes requiring a dose review.[4]
Stimulants (amphetamines, cocaine) Additive rise in heart rate and blood pressure with other sympathomimetics or stimulants.[4]

Contraindications

Cardiovascular disease, hypertension or arrhythmia recent myocardial infarction, unstable angina or serious arrhythmia (relative: weigh against continued smoking), or uncontrolled hypertension.[4]
Pregnancy or breastfeeding[4]
Children (age-restricted; respiratory-depression risk) keep concentrated nicotine or e-liquid away from children and pets (acute poisoning risk).[6]
Usage & Context
  • Used overwhelmingly as a recreational/dependence drug: smoked (cigarettes, cigars), vaped (e-cigarettes), or taken as oral/nasal tobacco (snus, chewing tobacco, snuff): for its stimulant-yet-relaxing effect and, in dependent users, to relieve withdrawal.
  • Also a medicine: nicotine-replacement therapy (patches, gum, lozenges, inhalers, nasal spray) delivers nicotine without tobacco smoke as an aid to stopping smoking.
  • Historically an agricultural insecticide, and a foundational molecule in pharmacology: the receptors it defines (the 'nicotinic' acetylcholine receptors) are named after it.
Sources & Evidence

Further Information