AdolescentsDepressive DisordersAnxiety DisordersPsilocybin

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance

This review article (2017) investigates the metabolism of psilocybin and psilocin (to which it metabolizes via dephosphorylation).

Authors

  • Dinis-Oliveira, R. J.

Published

Drug Metabolism Reviews
meta Study

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 the 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.

Available with Blossom Pro

Research Summary of 'Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance'

Introduction

Hallucinogens produce dose-dependent alterations in perception, thought and mood without markedly depressing or stimulating psychomotor function; sensory distortions such as synesthesia are common but frank hallucinations are not always present. Psilocybin and its dephosphorylated form psilocin are tryptamine-based indole alkaloids present in many Psilocybe and related mushroom genera; both act primarily at serotonin (5-HT) receptors, notably 5-HT2A, and have low abuse potential compared with other classes of psychoactives. While historically used recreationally, renewed clinical interest has arisen because of preliminary therapeutic signals for anxiety, depression and certain addictions, alongside continuing forensic concerns about acute toxic effects and variable individual responses. Dinis-Oliveira set out to review the metabolic fate of psilocybin and psilocin, with particular attention to major and minor metabolites that are relevant for clinical pharmacology and forensic toxicology. The review aims to collate human and non-human metabolic data, indicate enzymatic pathways and principal urinary metabolites, and discuss implications for detection, pharmacodynamics and potential drug interactions.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Full Text PDF

Full Paper PDF

Create a free account to open full-text PDFs.

Study Details

References (11)

Papers cited by this study that are also in Blossom

Psilocybin for treating substance use disorders?

de Veen, B. T. H., Schellekens, A., Verheij, M. M. et al. · Expert Review of Neurotherapeutics (2016)

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)

Human hallucinogen research: guidelines for safety

Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)

Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)

A review of the clinical effects of psychotomimetic agents

Osmond, H. · Annals of the New York Academy of Sciences (2010)

296 cited
The pharmacology of psilocybin

Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)

Recreational Use, Analysis and Toxicity of Tryptamines

Tittarelli, R., Mannocchi, G., Pantano, F. et al. · Current Neuropharmacology (2015)

Psilocybin - Summary of knowledge and new perspectives

Tylš, F., Páleníček, T., Horacek, J. · European Neuropsychopharmacology (2013)

Show all 11 references
Harm potential of magic mushroom use: A review

Van Amsterdam, J., Opperhuizen, A., Van Den Brink, W. · Regulatory Toxicology and Pharmacology (2011)

169 cited

Cited By (21)

Papers in Blossom that reference this study

Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants

Mueller, L., Klaiber, A., Ley, L. et al. · Clinical Pharmacokinetics (2025)

Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial

Bradley, E. R., Sakai, K., Fernandes-Osterhold, G. et al. · Neuropsychopharmacology (2025)

10 cited
Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study

Fink-Jensen, A., Jensen, M. E., Stenbæk, D. S. et al. · Journal of Psychopharmacology (2025)

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

Rouaud, A., Calder, A. E., Hasler, G. · Journal of Psychopharmacology (2024)

Drug-drug interactions involving classic psychedelics: A systematic review

Halman, A., Kong, G., Sarris, J. et al. · Journal of Psychopharmacology (2023)

40 cited
Therapeutic use of psilocybin: Practical considerations for dosing and administration

MacCallum, C. A., Pistawka, C. A., Deol, J. K. et al. · Frontiers in Psychiatry (2022)

Show all 21 papers
Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Stoliker, D., Egan, G. F., Friston, K. J. et al. · Pharmacological Reviews (2022)

Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity

Barr, A. M., Huang, J., Pham, M. et al. · Frontiers in Psychiatry (2022)

17 cited
Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro

Smedfors, G., Glotfelty, E., Papatziamos, C. et al. · Research Square (2022)

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review

Sarparast, A., Thomas, K., Malcolm, B. et al. · Psychopharmacology (2022)

Beating Pain with Psychedelics: Matter over Mind?

Elman, I., Borsook, D., Pustilink, A. · Neuroscience and Biobehavioral Reviews (2022)

Psychedelics as a Novel Approach to Treating Autoimmune Conditions

Thompson, C., Szabo, A. · Immunology Letters (2020)

The Emerging Role of Psilocybin and MDMA in the Treatment of Mental Illness

Gill, H., Gill, B., Chen-Li, D. et al. · Expert Review of Neurotherapeutics (2020)

Psychedelics and Psychedelic-Assisted Psychotherapy

Reiff, C. M., Richman, E. E., Nemeroff, C. B. et al. · American Journal of Psychiatry (2020)

Metabolism of lysergic acid diethylamide (LSD): an update

Libânio Osório Marta, R. F. · Drug Metabolism Reviews (2019)

DARK Classics in Chemical Neuroscience: Psilocybin

Geiger, H. A., Wurst, M. G., Daniels, R. N. · ACS Chemical Neuroscience (2018)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.