Nicotine

What it is

Nicotine is the substance in tobacco that keeps people smoking; it acts on nicotinic acetylcholine receptors in the brain [1]. It is also sold on its own as nicotine replacement therapy (NRT) — patches, gum, lozenges, sprays and inhalators — to help people stop smoking, and every licensed form raised quit rates in trials [2].

How it might work

Researchers propose that nicotine binds to nicotinic acetylcholine receptors and triggers the release of signalling chemicals including dopamine in the brain, which is thought to underlie both its addictive pull and its effects on attention and mood [1].

What the research says

The best-studied benefit is help with quitting smoking. A Cochrane review of 133 randomised trials with 64,640 smokers found every licensed form of nicotine replacement increased long-term abstinence compared with placebo or no help; the pooled risk ratio was 1.55, which the review describes as raising the rate of quitting by 50% to 60% [2]. Among pregnant smokers, NRT raised quitting near delivery in six pooled trials (RR 1.32), a benefit that was no longer statistically significant after birth [2].

For attention, a 2021 meta-analysis of 31 laboratory studies in 978 healthy non-smoking adults found nicotine patches improved overall cognitive scores and attention (effect sizes about 0.23) but not memory [3]. An earlier meta-analysis of 41 double-blind laboratory studies found small positive effects on six of nine performance areas, including alerting attention, fine motor skill and short-term memory, with effect sizes of 0.16 to 0.44 [4]. Gains concentrate in people with lower starting attention: in a trial of 62 non-smoking men, a 7 mg nicotine patch improved sustained attention in the low-attention group but slightly impaired strategy learning in the high-attention group [5]. Small trials in people with ADHD found improved response inhibition in 15 young adults [6] and lower symptom severity in 40 adults [7]. A systematic review of 29 studies in people with schizophrenia found single doses improved attention, working memory and executive function [8].

In ulcerative colitis, transdermal nicotine beat placebo for active disease in the 1990s — in a six-week trial of 72 people, 17 of 35 on nicotine patches reached complete remission versus 9 of 37 on placebo [9], and a pooled analysis of two trials found remission in 19 of 71 on nicotine versus 9 of 70 on placebo [10] — but it was no better than standard steroid or mesalazine treatment, and a later meta-analysis found no significant remission benefit while confirming more side effects [10][11]. It did not prevent relapse over six months [12], and 6 mg nicotine enemas did not work [13].

Doses used in studies

These are doses used in studies, not recommendations. Quitting trials used the licensed forms of nicotine replacement, from patches to gum and lozenges [2]. Ulcerative colitis trials used transdermal patches of 15 to 25 mg per day for 4 to 6 weeks [9][10], or 6 mg enemas [13]. Cognition studies gave nicotine as a single patch during laboratory sessions — for example, a 7 mg patch for six hours [5] — not as a daily routine.

Safety and interactions

Common side effects: skin irritation from patches and irritation inside the mouth from gum and lozenges; nausea, lightheadedness, headache and sleep problems also occur [2][9].

Heart: pooled trials found chest pain or palpitations more often with nicotine replacement than with placebo (odds ratio 1.88), though these were rare and serious heart events were extremely rare — including in people at high cardiovascular risk, where 1.2% had a serious event, no different from placebo [2][14]. Side effects also limit how much nicotine patients tolerate: in the colitis trials, people on nicotine were about six times more likely to stop treatment because of adverse events than those on placebo [10].

Toxic doses: high doses of nicotine are poisonous. Swallowing e-liquid has caused severe, potentially fatal poisoning [15], and poisoning from nicotine-containing plants follows a two-phase pattern — first abdominal pain, high blood pressure, fast heart rate and tremors, then low blood pressure, slow heart rate, breathing difficulty and coma [16]. Keep e-liquids and nicotine products away from children [15].

Pregnancy and breastfeeding: nicotine crosses the placenta and passes into breast milk [16]. Reviews of nicotine replacement in pregnancy cannot say whether it harms the fetus or not: compared with smoking, some outcomes looked better (birth weight, preterm birth) and some worse (miscarriage, stillbirth), but confidence in the findings was low to very low [17].

Medicines: because tobacco smoke speeds up the liver enzymes that clear some drugs, stopping smoking can raise drug levels within days, so people on medicines with a narrow safety margin may need a dose check [18]. Nicotine is addictive: dependence is the main reason not to start using nicotine products for casual benefits [1].

Caveats and open questions

The cognition findings come from single-dose laboratory studies, mostly in small groups, so nothing is known about lasting effects in healthy people [3][5]. The ulcerative colitis evidence is old, small and conflicting [11]. Whether nicotine or related drugs could ever work as treatments for attention problems is open: the trials so far used single doses or about a week of treatment [6][19].