Nicotine

TL;DR. The single most important fact about smoking is that nicotine is what keeps people smoking, and it is not what kills them. The cancer, the heart disease, and the COPD come overwhelmingly from the products of burning tobacco, not from the nicotine. That distinction is the entire basis of harm reduction, and it is badly understood: surveys repeatedly find most smokers and a majority of doctors wrongly believe nicotine itself causes most smoking-related cancer. Nicotine is not harmless, particularly in pregnancy and adolescence, and it is far less harmful than smoke.

1. What nicotine is

An alkaloid produced by the tobacco plant (Nicotiana tabacum) as an insecticide (Chapter 1). Small amounts occur in other nightshades: tomatoes, potatoes, and aubergines, at levels thousands of times too low to matter.

Mechanism: it binds nicotinic acetylcholine receptors in the brain and elsewhere, mimicking acetylcholine. In the ventral tegmental area it triggers dopamine release in the nucleus accumbens, which is the core reward pathway. It also releases noradrenaline, serotonin, and beta-endorphin.

Effects: alertness and improved attention, mild euphoria, appetite suppression, reduced anxiety in dependent users (largely by relieving withdrawal), and increased heart rate and blood pressure.

Why cigarettes are so addictive is largely a delivery-speed story. Inhaled nicotine reaches the brain in 10 to 20 seconds, faster than intravenous injection, because it goes lungs → pulmonary veins → left heart → brain without a detour. That speed produces a tight, repeated association between the act and the reward, roughly 200 times a day for a 20-a-day smoker, over years. Slower delivery routes (patches, gum, lozenges) are far less reinforcing, which is exactly why they are used as treatments rather than substitutes for the ritual.

Half-life is about 2 hours, which is why smokers reach for the next one every 30 to 60 minutes: levels fall below the threshold that prevents withdrawal.

2. What actually causes the harm

Cigarette smoke contains around 7,000 chemicals, of which roughly 70 are known carcinogens.

The scale of the harm: smoking kills more than 8 million people a year worldwide. Around half of long-term smokers die of a smoking-related disease, and the classic British Doctors Study found smokers lost around 10 years of life expectancy on average, with those quitting before 40 avoiding most of the excess risk.

Diseases caused: lung cancer (roughly 85 percent of cases), cancers of the mouth, throat, oesophagus, bladder, kidney, pancreas, stomach, cervix, and blood; COPD; coronary heart disease; stroke; peripheral arterial disease; aortic aneurysm; type 2 diabetes; macular degeneration; osteoporosis; rheumatoid arthritis; erectile dysfunction; and reduced fertility.

Quitting works, and fast:

Quitting at any age helps, and quitting before 40 avoids roughly 90 percent of the excess mortality.

3. Harm reduction, and the argument about it

The premise: if nicotine is what people want and smoke is what kills them, delivering nicotine without combustion should reduce harm enormously.

The evidence on e-cigarettes:

• Public Health England (now OHID) concluded vaping is around 95 percent less harmful than smoking. The specific figure has been criticised as based on expert judgement rather than direct measurement; the direction is not seriously contested.
• The Royal College of Physicians and the Cochrane review both support e-cigarettes as cessation aids. The 2024 Cochrane review found high-certainty evidence that nicotine e-cigarettes increase quit rates compared with nicotine replacement therapy.
• The Hajek trial (NEJM, 2019) randomised nearly 900 smokers and found e-cigarettes roughly doubled quit rates versus NRT.
• Biomarker studies show large reductions in exposure to carcinogens and toxicants in smokers who switch completely.

The genuine concerns, which are also real:

• Youth uptake. Vaping among adolescents rose substantially, driven by flavours, marketing, and discreet high-nicotine devices. Whether it acts as a gateway to smoking or a diversion from it is contested; smoking rates in young people have continued to fall in most countries where vaping rose, which is evidence against a strong gateway effect.
• Long-term effects are unknown. These products have been in wide use for about 15 years. Cancer takes decades. "Much safer than smoking" is well supported; "safe" is not established.
• EVALI. The 2019 US outbreak of severe lung injury, with 68 deaths, was traced to vitamin E acetate in illicit THC vaping products, not to nicotine e-liquids. It was widely misreported as caused by vaping generally, and that misreporting increased the proportion of smokers who wrongly believe vaping is as dangerous as smoking.
• Disposable vapes are an environmental problem (lithium batteries in landfill) and are being banned in several countries.
• Dual use. Someone who vapes and still smokes gets little benefit.

Other reduced-harm products: Snus, a Swedish oral tobacco pouch, is the most-studied case. Sweden has the lowest smoking rate and among the lowest lung cancer rates in Europe, widely attributed to snus displacing cigarettes. It is banned in the EU outside Sweden, which is a policy that is hard to justify on harm grounds. Nicotine pouches (tobacco-free) are newer and less studied. Heated tobacco heats rather than burns, reducing but not eliminating combustion products.

The honest position: if you smoke, switching completely to vaping or another non-combustible product is a large reduction in harm. If you do not use nicotine, do not start. Both statements are true and they are frequently treated as if only one can be.

4. Nicotine's own harms

Not zero, and worth stating precisely:

• Addiction, which is substantial.
• Cardiovascular: acutely raises heart rate and blood pressure and causes vasoconstriction. The contribution of nicotine alone to long-term cardiovascular disease appears small compared with carbon monoxide and oxidative damage, and it is not nothing.
• Pregnancy: nicotine itself impairs fetal brain and lung development and is associated with low birth weight. Nicotine in any form should be avoided in pregnancy where possible, though NRT is preferred to continued smoking if a woman cannot quit, because smoke is worse.
• Adolescent brain development: the prefrontal cortex matures into the mid-twenties, and animal and observational data suggest nicotine exposure during this period affects attention, impulse control, and susceptibility to later addiction. This is the strongest argument for keeping nicotine away from teenagers.
• Wound healing and bone healing are impaired by nicotine's vasoconstriction, which is why surgeons ask patients to stop before operations.
• Acute toxicity: see below.

5. Poisoning

Nicotine is acutely toxic. The classically cited lethal dose of 30 to 60 mg for an adult is now thought to be a substantial overestimate, deriving from dubious nineteenth-century self-experiments; more recent analysis suggests 0.5 to 1 g. It is still a poison.

The genuine hazards:

• E-liquid ingestion, particularly by children. Concentrated e-liquid can contain 20 mg/mL or more, and a small bottle can deliver a dangerous dose to a toddler. Poison centre calls rose sharply with vaping's growth. Child-resistant packaging is mandatory in most jurisdictions and the bottles are still often flavoured and brightly coloured.
• Nicotine pouches and gum, which look like sweets.
• Green tobacco sickness: an occupational illness in tobacco harvesters absorbing nicotine through wet skin from the leaves, causing nausea, vomiting, dizziness, and weakness. A genuine and under-recognised agricultural health issue.
• Nicotine patches on children, or multiple patches.

Symptoms of poisoning: nausea, vomiting, salivation, abdominal pain, sweating, dizziness, tachycardia then bradycardia, tremor, confusion, seizures, and respiratory failure.

If a child may have ingested e-liquid or nicotine products, call emergency services or a poisons centre immediately.

6. Quitting: what works

From Chapter 80, with detail:

Practical points:

• Start NRT before quit day for patches; use fast-acting forms for cravings on top.
• Most people underdose NRT and use it for too short a time. It is safe, and using more of it for longer is generally better than relapsing.
• Cravings last 3 to 5 minutes. Riding them out is a learnable skill.
• Withdrawal peaks in the first week and largely settles in 2 to 4 weeks: irritability, anxiety, poor concentration, increased appetite, low mood, and insomnia.
• Weight gain of 4 to 5 kg on average is common, from restored appetite and metabolic rate. Its health cost is trivially small compared with continuing to smoke, and being warned about it in advance helps.
• Relapse is normal. Most successful quitters made several attempts; each one raises the chance the next succeeds.
• Tell your prescriber if you take clozapine, theophylline, olanzapine, or several other drugs, because stopping smoking raises their blood levels by removing CYP1A2 induction, sometimes into the toxic range (Chapter 84). This is the single most important and least known medical fact about quitting.

7. The bottom line

• Nicotine is what makes people smoke; the smoke is what kills them. Most smokers, and many clinicians, believe otherwise, and that misconception keeps people smoking.
• Cigarette smoke contains roughly 7,000 chemicals and 70 known carcinogens. Half of long-term smokers die of a smoking-related disease, and quitting before 40 avoids most of the excess risk.
• Vaping is substantially less harmful than smoking, outperforms NRT for quitting in randomised trials, and has unknown long-term effects. If you smoke, switch completely; if you do not use nicotine, do not start.
• EVALI was caused by vitamin E acetate in illicit THC products, not nicotine e-liquid, and the misreporting did lasting damage.
• Nicotine itself is not harmless: it is addictive, harmful in pregnancy, and affects the adolescent brain, and e-liquid is acutely poisonous to children.
• Combination NRT plus behavioural support is the standard best approach; most people underdose and undertreat.
• Quitting smoking raises clozapine and theophylline levels dangerously. Tell your prescriber.

Sources and notes

Nicotine pharmacology, delivery speed by route, and dependence follow standard addiction medicine references and the US Surgeon General's reports. Cigarette smoke constituent counts and carcinogen numbers follow the IARC Monographs and the Surgeon General's 2010 report. Mortality and life expectancy figures follow Doll et al.'s British Doctors Study, BMJ, 2004, and Jha et al., NEJM, 2013, for the benefit of quitting before 40. The quitting timeline follows the Surgeon General and NHS summaries. The 95 percent relative harm reduction estimate for vaping follows the Public Health England 2015 evidence review and its 2018 update, with the noted criticism that the figure derived from expert judgement. Cochrane's 2024 e-cigarette review found high-certainty evidence that nicotine e-cigarettes increase quit rates versus NRT (Lindson et al.); the randomised trial is Hajek et al., NEJM, 2019. EVALI's attribution to vitamin E acetate in illicit THC products follows the CDC's 2020 final investigation. Snus and Swedish tobacco harm reduction follows Ramström and Foulds' analyses. Nicotine's effects in pregnancy and on the adolescent brain follow the Surgeon General's 2016 youth e-cigarette report. Nicotine acute toxicity and the revision of the classical lethal dose follows Mayer, Archives of Toxicology, 2014. Green tobacco sickness follows occupational health literature. Smoking cessation efficacy comparisons follow Cochrane reviews. Clozapine and theophylline level changes on quitting follow CYP1A2 induction pharmacology.

Open questions. Long-term health effects of vaping are genuinely unknown, because the products have been in wide use for only about 15 years and cancer takes decades. Whether youth vaping acts as a gateway to smoking or diverts from it remains contested.

👉 Next: food additives.