Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance

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.

Keywords:

• Psilocybin
• psilocin
• metabolomics
• metabolism
• toxicity
• toxicokinetics

Acknowledgements

Ricardo Dinis-Oliveira acknowledges Fundação para a Ciência e a Tecnologia (FCT) for his Investigator Grant (IF/01147/2013). This work was supported by FEDER under Program PT2020 (project 007265 – UID/QUI/50006/2013).

Disclosure statement

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Ricardo Dinis-Oliveira acknowledges Fundação para a Ciência e a Tecnologia (FCT) for his Investigator Grant (IF/01147/2013). This work was supported by FEDER under Program PT2020 (project 007265 – UID/QUI/50006/2013).