psilocybins

Psilocybins are psychoactive compounds produced by certain mushrooms, most notably the ester psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and related tryptamines. Psilocybin itself is a prodrug; after ingestion it is dephosphorylated to psilocin, the active agent responsible for the psychedelic effects.

Natural occurrence and sources: Psilocybin occurs in more than a dozen genera, especially in Psilocybe, but also in Panaeolus, Gymnopilus, and others. Concentrations vary by species, fruiting body maturity, and environmental conditions. These mushrooms have a long history of both traditional and modern use in various cultures and subcultures.

Pharmacology and effects: Psilocybin is rapidly converted to psilocin in the body. Psilocin acts as a serotonin receptor agonist, with strong activity at the 5-HT2A receptor, along with activity at 5-HT1A and 5-HT2C receptors. This activity modulates cortical networks, producing altered perception, mood, thought, and sense of self. The onset is typically 20–60 minutes after ingestion, with peak effects in 2–3 hours and a total duration of about 4–6 hours. Metabolites are excreted in urine.

Uses, research, and clinical context: Historically used in indigenous Central and South American rituals, psilocybins regained scientific interest in the mid-20th century and again in the 2010s for research into anxiety, depression, obsessive-compulsive disorder, and substance use disorders. Several trials have reported rapid antidepressant effects in controlled settings, often as part of guided psychedelic-assisted therapy. Regulatory pathways in some jurisdictions have opened to supervised clinical use, though access remains restricted elsewhere.

Safety and legal status: Adverse effects can include nausea, vomiting, anxiety, confusion, and paranoia; there is a risk of prolonged psychosis in predisposed individuals. Psilocybins are generally contraindicated for people with personal or family histories of schizophrenia or bipolar disorder, and there can be interactions with serotonergic medications. Legal status varies globally, with possession and sale illegal in many places, while some regions have decriminalized possession or permit supervised clinical use.