Recreational Drugs

TL;DR. This chapter exists because a book about everything that goes into your body cannot honestly stop at the legal ones, and because the harms that kill people are usually not the ones they expect. The dominant risk in illicit drug use today is not knowing what you have taken: illicit fentanyl and nitazenes contaminate supplies sold as heroin, oxycodone, and benzodiazepines, and they kill at microgram doses. The other dominant risk is combining depressants. This is harm reduction information, not encouragement.

1. Why this is in the book

Around one in twenty adults worldwide uses an illicit drug each year, and far more use alcohol, nicotine, and caffeine, which are pharmacologically drugs and culturally not (Chapters 61, 88, 89).

The legal categories do not track the harm. The 2010 Nutt and colleagues multi-criteria analysis in The Lancet, which scored drugs on harm to users and to others, put alcohol at the top of the combined harm ranking, above heroin and crack cocaine, largely because of harm to others. The paper was contested on methodology and it is a serious attempt to rank harm on evidence rather than legal schedule.

Information reduces harm. The evidence that abstinence-only drug education fails is substantial, and harm reduction measures (needle exchange, naloxone distribution, drug checking, supervised consumption) have well-documented effects on deaths and disease transmission.

2. How drugs are classified pharmacologically

The single most important pharmacological rule: combining depressants multiplies respiratory depression. Alcohol plus opioids plus benzodiazepines plus gabapentinoids is the combination behind a large share of drug deaths, and each additional agent is more than additive (Chapter 68).

3. The contamination crisis

This is the most important thing in this chapter.

Illicitly manufactured fentanyl and its analogues are extraordinarily potent: fentanyl is roughly 100 times morphine, and carfentanil around 10,000 times. Nitazenes, a newer class, are in some cases more potent still.

They contaminate the illicit supply, and are pressed into counterfeit tablets sold as oxycodone, Xanax, and diazepam that are visually indistinguishable from pharmaceutical products.

Why that is so lethal: the active dose is measured in micrograms, and mixing at that scale outside a pharmaceutical plant is unreliable. The "chocolate chip cookie" effect means one tablet from a batch can contain many times the dose of another. Someone taking what they believe is a benzodiazepine can receive a fatal opioid dose.

North America has seen over 100,000 overdose deaths a year, the majority involving synthetic opioids. The UK and Europe have seen rising nitazene-related deaths since 2023, and Ireland, Scotland, and England have issued repeated alerts.

The practical consequences, and they apply regardless of what you think you are taking:

• Never use alone. Most fatal overdoses happen with nobody present.
• Carry naloxone. It works on fentanyl and nitazenes, though repeated doses are often needed because of their potency and duration. It is free in many places, harmless if given unnecessarily, and available without prescription in many jurisdictions (Chapter 68).
• Test doses. Take a fraction first and wait.
• Fentanyl test strips detect fentanyl in a sample; they do not reliably detect all analogues or nitazenes.
• Drug checking services exist in several countries and substantially change behaviour when results show unexpected contents.
• Never assume a tablet is what it looks like. Counterfeits are visually perfect.

4. The specific drugs, briefly and factually

Cannabis

THC is the main psychoactive component; CBD is non-intoxicating and appears to moderate some of THC's effects.

Established harms: impaired driving (roughly doubles crash risk), respiratory symptoms from smoking, cannabis hyperemesis syndrome (cyclical severe vomiting relieved characteristically by hot showers, and frequently misdiagnosed for years), dependence in roughly 9 percent of users overall and higher in those starting young, and a dose-dependent association with psychosis.

On psychosis: the association is consistent and strongest for high-potency products and for early adolescent onset. The 2019 Di Forti multicentre study found daily use of high-potency cannabis associated with roughly a fivefold increase in psychotic disorder risk. Causation versus reverse causation and shared vulnerability remains argued, and the association is not in doubt.

Potency has risen substantially: average THC content in seized cannabis has roughly tripled over recent decades while CBD content has fallen, so "cannabis" today is not the same product studied in older research.

Medical cannabis has genuine evidence for chemotherapy-induced nausea, some chronic pain, spasticity in multiple sclerosis, and, for cannabidiol specifically, for certain severe childhood epilepsies, where it is a licensed medicine. That is a much narrower list than dispensary marketing suggests.

Edibles are the commonest route to emergency presentations: onset takes 30 to 120 minutes, people redose thinking it is not working, and the eventual effect is overwhelming. Paediatric poisonings from edibles that look like sweets have risen sharply.

Cocaine

A potent stimulant blocking dopamine, noradrenaline, and serotonin reuptake.

The acute risks are cardiovascular: it causes coronary vasospasm, hypertension, tachycardia, and arrhythmia. Cocaine-related chest pain is a common emergency presentation and can be a genuine myocardial infarction in a young person with clean arteries. Risk of MI is elevated many-fold in the hour after use. Stroke, aortic dissection, and seizures also occur.

Cocaine plus alcohol produces cocaethylene in the liver, a metabolite with a longer half-life and greater cardiotoxicity than cocaine itself. This combination is associated with substantially higher sudden death risk and is extremely common.

Chronic: nasal septum perforation, dependence, mood disturbance. Levamisole, a veterinary antiparasitic used as an adulterant in most seized cocaine, causes agranulocytosis and a characteristic vasculitis.

MDMA

Releases serotonin, dopamine, and noradrenaline massively.

The deaths are usually not from the drug's direct toxicity. The main mechanisms are:

• Hyperthermia: MDMA impairs thermoregulation, and prolonged dancing in hot venues causes core temperatures that cause multi-organ failure. Take breaks, stay cool.
• Hyponatraemia: the classic and under-known one. MDMA causes SIADH (inappropriate ADH release), so water is retained, and drinking large volumes of plain water dilutes blood sodium to the point of cerebral oedema and death. It has killed young people who did exactly what they were told. The guidance is roughly 500 mL of water per hour if active, less if not, and to include electrolytes.
• Serotonin syndrome, especially combined with SSRIs, MAOIs, or tramadol (Chapter 84).
• Contamination and dose variability: tablet strengths have risen substantially, and one "pill" is no longer a standard unit.

The mid-week comedown is a real serotonin depletion effect and is the basis of the folk advice to space use by months.

MDMA-assisted psychotherapy for PTSD has been through phase 3 trials with substantial effect sizes; the FDA declined approval in 2024 over trial design and blinding concerns, and research continues.

Ketamine

A dissociative anaesthetic, and simultaneously a rapidly growing recreational drug and a licensed treatment for treatment-resistant depression (as esketamine nasal spray, in supervised settings).

The distinctive chronic harm is urological. Ketamine-induced uropathy causes severe bladder inflammation, contraction, and ulceration, with urinary frequency, pain, and incontinence, and in severe cases requires bladder removal. It occurs in young, otherwise healthy heavy users and is frequently irreversible. Also causes abdominal pain ("K cramps") and liver and bile duct injury.

Acute risk: the dissociated state impairs judgement and coordination severely; drowning, falls, and choking on vomit are real. It combines dangerously with alcohol and other depressants.

Nitrous oxide

Widely used, widely assumed harmless, and it is not.

It irreversibly oxidises the cobalt in vitamin B12, inactivating it. Heavy use causes functional B12 deficiency and subacute combined degeneration of the spinal cord: numbness, tingling, weakness, unsteady gait, and, if not treated early, permanent neurological disability in young people. Cases have risen substantially and are now a recognised neurology presentation.

Also: asphyxiation if inhaled without oxygen or from a closed system, frostbite injuries from direct canister inhalation, and rare pneumothorax.

B12 supplementation does not prevent the damage in heavy users; stopping does. Anyone using regularly with any neurological symptom needs urgent assessment.

Psychedelics

LSD, psilocybin, DMT. Physiologically among the least toxic drugs with very high therapeutic indices and no dependence liability in the usual sense.

The risks are psychological and situational: acute anxiety and panic ("bad trips"), dangerous behaviour while impaired, precipitating or worsening psychosis in vulnerable people (a contraindication in personal or family history of psychotic illness), and hallucinogen persisting perception disorder, which is rare.

Serotonin syndrome risk with SSRIs, MAOIs, and lithium, and lithium in particular is associated with seizures when combined with psychedelics.

Research context: psilocybin for treatment-resistant depression has produced striking phase 2 results and is in phase 3 trials, in controlled settings with psychological support that bear little resemblance to recreational use.

Synthetic cannabinoids ("spice")

Far more dangerous than cannabis, despite the name. They are full agonists at the CB1 receptor where THC is a partial agonist, producing much stronger and less predictable effects: psychosis, seizures, acute kidney injury, arrhythmia, and death. Potency varies wildly between batches. They are prevalent in prisons and among homeless populations partly because they were historically not detected on standard drug tests.

GHB/GBL

A depressant with an extremely narrow margin between the recreational dose and unconsciousness, measured in millilitres. Combined with alcohol it is frequently fatal. Withdrawal in dependent users is a medical emergency comparable to severe alcohol withdrawal, with delirium and seizures.

5. General harm reduction

If someone is going to use, these reduce deaths:

1. Never use alone, or use a service like a supervised consumption facility or an overdose prevention hotline.
2. Carry naloxone and know how to use it. Opioid contamination affects everything now.
3. Start low, go slow. Take a fraction and wait, especially with a new batch or after a break.
4. Never mix depressants: alcohol, opioids, benzodiazepines, GHB, gabapentinoids.
5. Tolerance falls fast after a break. Overdose deaths cluster after release from prison, hospital, or treatment.
6. Test what you have where drug checking or reagent testing is available.
7. Do not drive.
8. Stay cool and hydrate sensibly, not excessively, on stimulants.
9. Know your medicines: SSRIs, MAOIs, tramadol, lithium, and HIV protease inhibitors all interact seriously.
10. Call for help and stay. Most jurisdictions have some form of Good Samaritan protection, and the alternative is someone dying.

Signs of opioid overdose: unresponsive, slow or absent breathing, pinpoint pupils, blue lips. Give naloxone, call an ambulance, put them in the recovery position, and stay.

Signs of stimulant emergency: chest pain, very high temperature, seizure, severe agitation, confusion. Call an ambulance, cool them, and stay.

6. If you want to stop

Dependence is a treatable medical condition, and the evidence-based treatments are effective:

• Opioid use disorder: methadone or buprenorphine roughly halve mortality (Chapter 68).
• Alcohol: medically supervised withdrawal where dependent (abrupt cessation can cause seizures and death), plus acamprosate, naltrexone, or disulfiram, plus psychosocial support.
• Stimulants: no licensed pharmacotherapy; contingency management has the best evidence.
• Cannabis: psychosocial approaches.
• Benzodiazepines: slow supervised taper, never abrupt (Chapter 77).

Dependence is not a moral failure, treatment works, and relapse is part of the usual course rather than evidence of failure.

7. The bottom line

• The legal classification of drugs does not track their harm. Alcohol scores at or near the top of evidence-based harm rankings, largely through harm to others.
• The dominant risk today is not knowing what you have taken. Fentanyl and nitazenes contaminate illicit supplies and are pressed into perfect-looking counterfeit tablets, at doses measured in micrograms.
• Combining depressants is the mechanism behind a large share of drug deaths.
• MDMA deaths are usually from hyperthermia or from water-induced hyponatraemia rather than direct toxicity. Cocaine plus alcohol makes cocaethylene and multiplies cardiac risk. Ketamine destroys bladders. Nitrous oxide inactivates vitamin B12 and causes spinal cord degeneration.
• Never use alone, carry naloxone, start low, and never mix depressants. Tolerance falls fast after a break, and that is when people die.
• Dependence is treatable, opioid agonist treatment halves mortality, and alcohol withdrawal in a dependent person can kill without medical support.

Sources and notes

The multi-criteria harm ranking placing alcohol highest is Nutt, King, and Phillips, The Lancet, 2010, with its published methodological critiques. Global prevalence follows the UNODC World Drug Report. Harm reduction evidence for needle exchange, naloxone distribution, drug checking, and supervised consumption follows WHO, EMCDDA, and Cochrane reviews. Fentanyl and nitazene contamination of illicit supply follows DEA, NCA, and EMCDDA alerts and national overdose surveillance. Cannabis and psychosis follows Di Forti et al., Lancet Psychiatry, 2019, the EU-GEI multicentre study; potency trends follow ElSohly's seizure analyses. Cannabis hyperemesis syndrome follows gastroenterology case literature. Medical cannabis evidence follows the US National Academies' 2017 review. Cocaethylene formation and cardiotoxicity follow Pennings, Leccese, and de Wolff's review; myocardial infarction risk in the hour after use follows Mittleman et al., Circulation, 1999; levamisole adulteration follows published case series. MDMA hyperthermia and SIADH-mediated hyponatraemia follow Hall and Henry, British Journal of Anaesthesia, 2006. MDMA for PTSD follows the MAPP1 and MAPP2 phase 3 trials and the FDA's 2024 complete response letter. Ketamine uropathy follows Chu et al.'s Hong Kong series and subsequent urology literature. Nitrous oxide B12 inactivation and subacute combined degeneration follow Garakani et al.'s review and rising UK neurology case reports. Psychedelic safety profiles and psilocybin depression trials follow Carhart-Harris and colleagues' work at Imperial and the COMPASS phase 2b trial. Synthetic cannabinoid harms follow EMCDDA reporting. Opioid agonist treatment mortality reduction is Sordo et al., BMJ, 2017.

Open questions. Whether cannabis causes psychosis or unmasks it in the vulnerable is not resolvable with current designs. Psychedelic trial blinding is close to impossible, which limits how much the results can be trusted.

👉 Next: how to read a scare headline.