Other Recreational Drugs: Cannabinoids, Hallucinogens, GHB and Inhalants

Cannabis: usually frightening, rarely fatal

The active ingredient, THC, is a partial agonist at the CB1 and CB2 cannabinoid receptors. CB1 receptors sit densely in the brain and account for the psychoactive effects; CB2 receptors sit mostly on immune cells. Natural cannabis intoxication is, for the toxicologist, reassuringly benign: anxiety and panic, a racing heart (tachycardia), red eyes, dry mouth, and impaired coordination. The classic emergency-department presentation is a first-time or high-dose user convinced they are dying of a heart attack — the treatment is a calm room, reassurance, and a small dose of a benzodiazepine if agitation demands it. Deaths from natural cannabis alone are vanishingly rare. There is, however, one distinctive syndrome worth its own heading: with heavy chronic use some people develop cannabinoid hyperemesis syndrome — recurrent, cyclical bouts of severe vomiting, paradoxically in the very drug reputed to stop nausea. The near-pathognomonic clue is that patients learn to relieve it with compulsive hot showers or baths. The definitive cure is stopping cannabis; topical capsaicin cream and antiemetics help in the acute attack, while ordinary antiemetics often disappoint.

Synthetic cannabinoids: the dangerous impostor

Sold as "Spice" or "K2" — herbal material sprayed with laboratory-made cannabinoids — these are an entirely different animal from the plant. Where THC is a partial agonist, most synthetic cannabinoids are full agonists at CB1, many times more potent, and their content is unpredictable batch to batch. The result is a toxidrome the natural drug almost never produces: severe agitation, psychosis, seizures, hyperthermia, acute kidney injury (AKI), and true fatalities, including from cardiac arrest. A patient may have smoked something they believed was "just weed" and arrive convulsing. Management is supportive and symptom-led — benzodiazepines for agitation and seizures, aggressive cooling for hyperthermia, and fluids with renal monitoring for AKI — but the essential lesson is to never extrapolate the safety of cannabis onto its synthetic cousins.

Classic hallucinogens: LSD and psilocybin

LSD and psilocybin (magic mushrooms) act as agonists at the 5-HT2A serotonin receptor. That single receptor action produces the whole psychedelic experience — visual distortions, synaesthesia, and a profoundly altered sense of self and time. Physically these drugs are remarkably safe: they cause mild sympathetic features (dilated pupils, mild tachycardia) but almost never kill by direct toxicity. The real danger is psychological: the "bad trip" — overwhelming panic, paranoia, and terrifying perceptual distortion. The management is famously low-tech: put the patient in a quiet, softly-lit room, provide calm reassurance and "talk-down" support from a steady person, and reserve a benzodiazepine for genuine agitation. Because the mechanism is serotonergic, keep serotonin syndrome in mind if the person has also taken other serotonergic agents — a theme explored in depth in the Central Nervous System chapter on 5-HT2A signalling and in the serotonin-syndrome discussion of the stimulant/MDMA chapter.

Dissociatives: ketamine and PCP

Ketamine and phencyclidine (PCP) work by a completely different mechanism: they are antagonists at the NMDA glutamate receptor. Blocking NMDA "disconnects" the cortex from sensory input, producing dissociation — a floating detachment from the body and environment — along with nystagmus (the give-away rotatory or vertical eye jerks), analgesia, and, at higher doses, catatonia or coma. Ketamine has a legitimate double life: it is a mainstay anaesthetic and analgesic, prized because it preserves airway reflexes and respiratory drive, and — as low-dose esketamine — it is now an established rapid-acting antidepressant for treatment-resistant depression, a use rooted in the same NMDA blockade discussed in the Central Nervous System chapter. PCP is the more dangerous sibling: it classically causes extreme agitation and violence with startling analgesia, dangerous hyperthermia, and rhabdomyolysis (muscle breakdown) that can precipitate acute kidney injury. For both, management is supportive — a calm environment, generous benzodiazepines for agitation, and, with PCP, active cooling and fluids while watching creatine kinase and renal function. NBOMe compounds and the ever-shifting roster of novel psychoactive substances (NPS) blur these categories further, often combining potent 5-HT2A agonism with unpredictable stimulant toxicity, so treat the toxidrome in front of you rather than the name on the bag.

GHB and GBL: the sudden coma with a sudden awakening

Gamma-hydroxybutyrate (GHB) is an agonist at GABA-B receptors (and its own GHB receptor). Sold as a clear, salty liquid and often taken at clubs (its industrial precursor GBL is converted to GHB in the body), it has a treacherously steep dose-response curve — the gap between a euphoric dose and a comatose one is small. The signature presentation is an abrupt, deep coma: a patient who is unrousable, with reduced respiration, mimicking an opioid overdose but not responding to naloxone. Then comes the most distinctive feature in all of toxicology — the sudden awakening: after a few hours the patient wakes abruptly, often agitated, and may want to walk straight out of the department. There is no specific antidote. Management is meticulous supportive care, above all protecting the airway until the drug wears off. The danger multiplies with co-ingested alcohol or other CNS depressants, which deepen the respiratory depression and can turn a self-limiting coma into a fatal one. Just as important, chronic heavy GHB use produces genuine physical dependence, and abrupt cessation triggers a severe withdrawal syndrome — tremor, agitation, autonomic storm, hallucinations and seizures — that closely mirrors alcohol (and benzodiazepine) withdrawal covered in the Ethanol chapter, and is treated the same way: with high-dose benzodiazepines.

Inhalants: solvents, nitrous oxide, and poppers

These are cheap, legal, and lethal in ways students rarely expect. Volatile substance misuse covers glue, aerosols, lighter gas, and paint thinners — inhaled for a brief euphoric high. The catastrophic risk is "sudden sniffing death": these hydrocarbons sensitise the myocardium to catecholamines, so a surge of adrenaline (from the fright of being caught, or sudden exertion) can trigger a fatal ventricular arrhythmia in an otherwise well teenager. The management implication is critical — avoid anything that raises catecholamines, keep the patient calm, and be extremely cautious with adrenaline. Nitrous oxide ("laughing gas", whippets) has become a huge recreational drug and hides a slow, specific poison: it irreversibly oxidises the cobalt core of vitamin B12, inactivating it. Heavy chronic use therefore produces functional B12 deficiency and subacute combined degeneration of the spinal cord — a progressive myeloneuropathy with numbness, tingling and unsteady gait — a striking overlap with the Hematology and Neurology chapters on B12 metabolism; treatment is stopping the gas and replacing B12. Finally, alkyl nitrites ("poppers", amyl/isobutyl nitrite) are potent vasodilators used for a head-rush and to relax smooth muscle. Their two toxic signatures are profound hypotension and — importantly — methaemoglobinaemia: the nitrite oxidises haemoglobin's iron to the ferric state, producing brown blood, cyanosis unresponsive to oxygen, and a low pulse-oximetry reading that doesn't fit. Severe cases are reversed with methylene blue (with the usual caution in G6PD deficiency), exactly as taught in the Methaemoglobinaemia chapter.