Nicotine

Nicotine is a naturally occurring alkaloid found predominantly in tobacco and in smaller amounts in other members of the nightshade family, including Duboisia hopwoodii, potatoes, tomatoes, and aubergines. It functions as a potent plant defence compound against herbivores, a property that historically made it valuable as an insecticide. In humans, nicotine is widely used as a stimulant and anxiolytic, and it is the primary addictive substance in tobacco products.
As a pharmaceutical agent, nicotine is used chiefly to assist with smoking cessation, helping to alleviate withdrawal symptoms through controlled therapeutic dosing. Recreational exposure derives primarily from tobacco smoking, vaping, smokeless tobacco use, and other nicotine-containing products.

Chemical and Pharmacological Properties

Nicotine acts primarily as an agonist at most nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels involved in neuromuscular and autonomic nervous system signalling. At two receptor subtypes, nAChRα9 and nAChRα10, nicotine acts instead as an antagonist. Its highest binding affinity is at the α4β2 receptor, implicated strongly in both cognitive effects and the drug’s addictive potential.
Absorbed nicotine acts rapidly on the central nervous system, producing heightened alertness, mood modulation, and mild anxiolysis. At low doses, it can exert a weak analgesic effect. Nicotine typically accounts for about 0.6–3.0% of the dry weight of tobacco leaves, and a typical cigarette delivers approximately 2 mg of absorbed nicotine.
Although small quantities occur naturally in edible plants of the Solanaceae family, these concentrations are extremely low, and their physiological significance for human consumers remains unclear.

Addictive Potential and Dependence

Nicotine is highly addictive, with dependence often developing rapidly. Features of addiction include tolerance, reverse tolerance in some cases, compulsive use, and withdrawal. Psychological dependence may manifest as irritability, anxiety, difficulty concentrating, sleep disturbances, and depressed mood.
Withdrawal symptoms tend to worsen sharply after cessation before gradually easing. Some evidence suggests that monoamine oxidase inhibitors present in tobacco smoke can amplify nicotine’s reinforcing properties, contributing to greater addiction severity in smokers compared with those using pure nicotine replacement products.
The estimated lower limit of a fatal dose in adults is around 500–1000 mg of ingested nicotine, though severe or fatal poisoning is rare. High doses can cause organ failure and respiratory paralysis.

Medical Uses

Nicotine’s principal medical application is in nicotine replacement therapy (NRT), designed to support individuals trying to stop smoking. Therapies may include:

• Nicotine gum,
• Transdermal patches,
• Lozenges,
• Oral inhalers, and
• Nasal sprays.

NRT delivers nicotine in slower, controlled amounts, reducing cravings without producing the intense reinforcement associated with rapid delivery systems such as cigarettes. Evidence from systematic reviews indicates that all forms of NRT increase the likelihood of quitting, and combining a patch with a fast-acting product yields higher success rates.
Although nicotine is not recommended during pregnancy or breastfeeding, its use as part of a cessation strategy is generally considered safer than continued smoking. In cardiovascular patients, NRT has not been shown to increase adverse events when compared with placebo.

Use as an Insecticide

Nicotine has been used since at least the seventeenth century as an insecticide, acting on insect nicotinic acetylcholine receptors. Its potency led to the development of modern neonicotinoid insecticides, such as imidacloprid, which are structurally similar and widely used in agriculture and veterinary practice.
Due to toxicity and environmental concerns, nicotine-based pesticides were banned in the European Union in 2009 and in the United States in 2014, including for organic farming applications. Neonicotinoids remain in use globally, although their ecological effects continue to be scrutinised.

Cognitive and Performance Effects

Nicotine has been studied for its potential nootropic effects. Meta-analytic evidence suggests that nicotine can improve certain cognitive functions, including fine motor skills, attention, and aspects of working and episodic memory. These effects are often associated with stimulation of α4β2 nicotinic receptors.
However, performance benefits are inconsistent, may follow an inverted-U pattern consistent with the Yerkes–Dodson law, and must be weighed against nicotine’s addictive properties.

Recreational Use

Nicotine is one of the most widely used psychoactive substances. Recreational users may consume it through:

• Cigarettes and cigars,
• E-cigarettes and vaping devices,
• Chewing tobacco,
• Snuff and snus,
• Nicotine pouches, and
• Novel preparations such as nicotine-infused alcoholic beverages.

Addiction can develop after only a short period of use, and sustained consumption poses significant health risks, largely due to the harmful effects of tobacco smoke rather than nicotine itself.

Contraindications and Safety Considerations

Nicotine used in therapeutic doses has relatively few contraindications, although caution is advised in specific populations:

• Adolescents: Effectiveness of NRT is uncertain, so its routine use is not recommended.
• Pregnancy and breastfeeding: Nicotine is considered safer than smoking but still carries risks, including associations with birth defects.
• Cancer treatment: Nicotine may promote tumour cell growth, but short-term NRT may still be advised for cessation purposes.
• Cardiovascular disease: Controlled studies generally find no significant increase in adverse events with NRT.

Nicotine gum and other oral products may have specific contraindications depending on dental health, gastrointestinal conditions, or concurrent medication use.