Pharmacokinetics of Psilocybin, a Tryptamine Alkaloid in Magic Mushroom ( Psilocybe cubensis ): A Systematic Review
Nilubon Thaoboonruang, Manupat Lohitnavy, Ornrat Lohitnavy
Journal of Psychoactive Drugs September 10, 2024 DOI: 10.1080/02791072.2024.2399128 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Pharmacokinetics Pharmacology Tryptamine Alkaloid Traditional medicine |
| Citations | 11 |
| Key findings | Psilocybin is a prodrug that is rapidly dephosphorylated to psilocin, which reaches peak plasma and brain levels in a dose-dependent manner and has a half-life of 2–3 hours. |
Abstract
Psilocybin, a major indole alkaloid found in magic mushrooms (Psilocybe cubensis), has recently drawn attention as a breakthrough therapy to treat major depressive disorder. This review aimed to summarize and identify knowledge gaps concerning their pharmacokinetic characteristics of psilocybin and its active metabolite, psilocin. Original studies related to pharmacokinetics of psilocybin conducted in vitro, animals, and humans were systematically collected from PubMed, Scopus, and ScienceDirect, from their inceptions to November 2023. Twenty articles were included in this work and assessed for study quality. A comprehensive review of the pharmacokinetics of psilocybin and psilocin in both animals and humans was performed. Psilocybin is considered a prodrug that is dephosphorylated to psilocin by alkaline phosphatase. Following ingestion, the peak psilocin plasma and brain levels were rapidly achieved in a dose-dependent manner. Psilocin is metabolized primarily through both Phase I and Phase II processes with the half-life of 2-3 hours. This review also identified lack of some pharmacokinetic related information and limitations of available research that may help direct future investigations to better understand the pharmacokinetics and improve study design including dose selection and dosage optimization.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| Blinding and expectancy confounds in psychedelic randomized controlled trials | 2021 | Systematic review | |
| Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials | 2016 | Systematic review | |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |
Citations in the library
Cited by 9
- Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models Frontiers in Systems Neuroscience August 5, 2025
- Age- and estrous-dependent effects of psilocybin in rats. Neuropharmacology November 15, 2025
- Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans. Scientific Reports April 21, 2025
- The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal ACS Pharmacology & Translational Science July 16, 2025
- Therapeutic Potential of Psilocybin in Psychiatric Disorders: Mechanisms, Efficacy, and Clinical Implications FOCUS: The Journal of Lifelong Learning in Psychiatry April 1, 2026
and 4 more in the library
Cites 32
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
and 27 more in the library