Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance

Psilocybin and psilocin, the main hallucinogenic compounds in magic mushrooms, act as agonists or partial agonists at 5-HT2A receptors. Psilocybin is a pro-drug dephosphorylated by alkaline phosphatase to the active metabolite psilocin, which is further metabolized; psilocin-O-glucuronide is the main urinary metabolite with clinical and forensic relevance. Considerable physiological variability between individuals influences dose-response and toxicological profiles. The review presents all major and minor psychoactive metabolites of psilocybin and psilocin.

Study at a glance

Abstract

Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.