Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance

Summary & key facts

This review explains how the main chemicals in magic mushrooms are changed by the body. It says psilocybin is turned into the active drug psilocin, both work on the brain's serotonin 2A receptor, and people vary a lot in how they break these chemicals down. The paper highlights that psilocin is further broken into other compounds, and that a breakdown product called psilocin-O-glucuronide shows up in urine and matters for medical and forensic testing.

Key facts:

• Psilocybin and psilocin are the two main hallucinogenic chemicals in “magic mushrooms,” and they are controlled substances in many countries.
• Both chemicals act on the brain’s serotonin 2A receptor (sometimes written 5-HT2A); this means they activate or partly activate a protein that changes brain signaling and is linked to hallucinations.
• Psilocybin itself is mainly a pro-drug, which means the body converts it into the active drug psilocin by removing a phosphate group with an enzyme called alkaline phosphatase.
• Psilocin is further broken down by the body. Its main breakdown product found in urine is psilocin-O-glucuronide, and that metabolite is useful for clinical diagnosis and forensic drug testing.
• People show considerable differences in their physiology, so how fast and fully they turn psilocybin into psilocin and other metabolites can vary a lot. That variation can affect how strong the drug feels and its toxicology.
• The review gathers the major and minor psychoactive metabolites known so far, which helps researchers and clinicians understand effects and improve testing.

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.

Topics

Chemical synthesis and alkaloids Forensic Toxicology and Drug Analysis Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Biology Chemistry Hallucinogen Pharmacology Psilocybin

Substances

Psilocybin