Psilocybin: chemistry

Psilocybin is a tryptamine alkaloid, the main hallucinogenic compound in Psilocybe mushrooms [1], found naturally across roughly 200 mushroom species [2]. It's a prodrug [3]: the body converts it to psilocin [1], and it's psilocin that does the work. Serotonergic agonist activity likely underlies psilocybin's bioactivity [1], and psilocybin induces profound alterations in consciousness through the 5-HT2A receptor [4]. Psilocybin's acute and persisting effects are a monotonically increasing function of dose, with significant effects seen even at the lowest dose tested [5].

Psilocin doesn't stick around long. Its half-life is 1.8 hours, ranging from 1.1 to 2.2 hours [6]. Psilocybin's effects are shorter-lived than LSD's even when the subjective intensity is comparable — 30 mg of psilocybin lines up with 100–200 µg of LSD in effect strength, but LSD lasts longer [7]. The two drugs also diverge on the body: psilocybin pushes blood pressure up more than LSD does, while LSD pushes heart rate up more than psilocybin does [7]. Beyond timing and those physiological differences, the character of the altered state itself doesn't differ between the two [7].

Psilocybin was first isolated and studied in the 1950s [8]. Albert Hofmann isolated it from Psilocybe mexicana in 1958 [3][2], decades after the mushrooms themselves had been used in Mesoamerican ritual practice [9]. Hofmann's synthesis route was later commercialized by Sandoz under the name Indocybin [9][10].

References

1. psilocybin | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY — IUPHAR/BPS
2. Psilocybin | Johns Hopkins Psychiatry Guide — Johns Hopkins Medicine
3. Psilocybin - American Chemical Society — American Chemical Society
4. Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin - PubMed — PubMed (journal article)
5. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects — Psychopharmacology (Springer)
6. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects — Clinical Pharmacology & Therapeutics (Wiley)
7. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects — Neuropsychopharmacology (Nature)
8. Psilocybin — Encyclopaedia Britannica
9. Psilocybin and hallucinogenic mushrooms | CNS Spectrums — Cambridge University Press
10. DARK Classics in Chemical Neuroscience: Psilocybin — ACS Chemical Neuroscience