🍄 Psilocybin

4-phosphoryloxy-N,N-dimethyltryptamine

Class: Tryptamine · Duration: 4–6 hours · Onset: 20–60 min · Source: 200+ mushroom species

Overview

Psilocybin is a naturally occurring prodrug — the body converts it to psilocin, which binds to serotonin 5-HT2A receptors. It's found in over 200 species of fungi, most famously in the Psilocybe cubensis and Psilocybe semilanceata (liberty cap) families.

Effects range from subtle perceptual shifts at low doses to full ego dissolution at high doses. Visual distortions, emotional intensity, synesthesia, and a sense of profound meaning are commonly reported.

History

Archaeological evidence suggests humans have used psilocybin mushrooms for at least 6,000 years. Aztec codices reference teonanácatl ("flesh of the gods"). R. Gordon Wasson's 1957 Life magazine article about Mazatec curandera María Sabina brought psilocybin to Western attention. Albert Hofmann isolated and synthesized psilocybin in 1958.

Pharmacology

Psilocybin is rapidly dephosphorylated to psilocin in the gut and liver. Psilocin is a partial agonist at 5-HT2A, 5-HT2C, and 5-HT1A receptors. The subjective effects correlate strongly with 5-HT2A occupancy. Tolerance builds rapidly (within days) and cross-tolerates with LSD and mescaline.

Therapeutic Research

Psilocybin-assisted therapy has shown remarkable results in clinical trials for treatment-resistant depression, end-of-life anxiety, addiction (tobacco, alcohol), and OCD. Johns Hopkins and Imperial College London have been at the forefront. The FDA granted "breakthrough therapy" designation for psilocybin for depression in 2018.

Harm Reduction

Set and setting are everything — environment and mindset shape the experience profoundly.
Start low, especially with unfamiliar sources. Potency varies dramatically between species and even flushes.
A trusted sitter is valuable, especially at higher doses.
Psilocybin has extremely low physiological toxicity — no known lethal dose in humans.
Psychological risk exists: challenging experiences ("bad trips") are possible and more likely at higher doses or in unsupportive settings.
Contraindicated with lithium. Caution with SSRIs (blunted effects, possible serotonin issues).