Nicotine

Nicotine is a stimulant and alkaloid that occurs naturally in nightshade plants, especially tobacco, and can also be made synthetically. People use it recreationally for its stimulating and anxiety-reducing effects. In tobacco leaves, it makes up about 0.6 to 3 percent of the dry weight, with tiny amounts found in other Solanaceae crops like tomatoes, potatoes, and eggplants. Pure nicotine is a colorless to yellowish oily liquid that easily crosses biological membranes and is a potent neurotoxin to insects, acting as a natural defense against herbivores. It was once widely used as an insecticide, and its chemical structure led to the development of synthetic neonicotinoid pesticides.

In humans, nicotine works mainly as a stimulant by binding to and activating nicotinic acetylcholine receptors (nAChRs) in the central nervous system and peripheral tissues. This triggers the release of neurotransmitters such as dopamine, acetylcholine, and norepinephrine, resulting in increased alertness, reduced anxiety, and mild euphoria. Nicotine is typically consumed through smoking tobacco, vaping, or other delivery systems. An average cigarette delivers about 2 mg of absorbed nicotine, enough to cause reinforcement and dependence but well below toxic levels.

Nicotine is highly addictive. Dependence involves tolerance, physical and psychological reliance, and withdrawal symptoms like irritability, anxiety, and trouble concentrating. Nicotine replacement therapy (NRT) products—such as gums, patches, and lozenges—deliver nicotine more slowly and in lower doses, making them less addictive and used medically to help people quit smoking. Synthetic derivatives like varenicline act as partial agonists at nicotinic receptors and are also used for smoking cessation.

Nicotine itself is not classified as a carcinogen by the International Agency for Research on Cancer or the U.S. Surgeon General. At high doses, it can cause poisoning and respiratory paralysis. It is a known teratogen, linked to harmful developmental effects during pregnancy, and may impair adolescent brain development, though the extent of this effect in humans is still debated.

**Medical uses** The main medical use of nicotine is treating nicotine dependence to help people stop smoking and avoid its health harms. Nicotine alone is not a standalone cessation tool; its effectiveness comes from NRT delivery systems, which vary in formulation—transdermal patches and lozenges for steady release, and oral gum, inhalers, and nasal sprays for acute relief—to control how much nicotine is absorbed and to mimic tobacco’s pharmacokinetics without harmful byproducts. A 2018 Cochrane review found strong evidence that all current NRT forms (gum, patch, lozenges, inhaler, nasal spray) increase quitting success by 50 to 60 percent, regardless of setting. Combining a nicotine patch with a faster-acting form like gum or spray improves success odds. Unlike recreational nicotine products, which are designed to maximize addiction, NRTs are designed to minimize addictiveness; the faster a dose is delivered and absorbed, the higher the addiction risk.

**Pesticide** Nicotine has been used as an insecticide since at least 1690, in tobacco extracts or as pure nicotine sulfate (though other tobacco components also have pesticide effects). It acts on the nicotinic acetylcholine receptor, which gave the receptor its name, and is classified in IRAC group 4B. Between 1915 and 1992, nicotine sulfate was sold as a home insecticide in the U.S. under the name "Black Leaf 40." Nicotine insecticides have been banned in the U.S. since 2014, including for organic crops, and are not recommended for small gardeners. They have been banned in the EU since 2009. Foods are imported from countries where nicotine pesticides are allowed, such as China, but must not exceed maximum nicotine levels. Neonicotinoids like imidacloprid are synthetic insecticides derived from nicotine and structurally similar. They are widely used in agriculture and veterinary medicine. Unlike traditional surface-applied nicotine pesticides, neonicotinoids are systemic—absorbed throughout the plant and cannot be washed off—which reduces worker exposure but requires timed applications to limit residues in food crops.

**Performance** Nicotine products are sometimes used for cognitive enhancement. A 2010 meta-analysis of 41 double-blind, placebo-controlled studies found that nicotine or smoking had significant positive effects on fine motor skills, alerting and orienting attention, and episodic and working memory. A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain attentional improvements; among nicotinic receptor subtypes, nicotine has the highest binding affinity at α4β2 (ki=1 nM), which also mediates its addictive properties. Nicotine has potential benefits but also paradoxical effects, possibly due to an inverted U-shaped dose-response curve or pharmacokinetic factors.

**Recreational** Nicotine is widely used recreationally through tobacco products, electronic cigarettes, and nicotine pouches. As of 2024, about 1.2 billion people worldwide use tobacco products. It is highly addictive and difficult to stop using. Nicotine is often used compulsively, and dependence can develop.