A total of 19 publications covering 12 unique clinical datasets were included in the review of 's .
Psilocybin is rapidly absorbed and transformed into psilocin after oral administration.
Psilocin exhibits biphasic concentration-time profiles, with a distribution volume ranging from 505 to 1267 L.
The terminal half-life of psilocin is between 1.23 and 4.72 hours.
Only 1.5-3.4% of the administered dose is excreted as psilocin in urine.
Psilocin is primarily converted to 4-hydroxyindole-3-acetic acid and, to a lesser extent, to conjugated psilocin.
Information on psilocin's absolute bioavailability is limited, with one study estimating it at 55%.
Simplified
BACKGROUND AND OBJECTIVE: Psilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, , is presented.
METHODS: The review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans. In addition, raw pharmacokinetic data from these studies was requested and/or extracted to further compare results across studies.
RESULTS: In total, 309 publications were identified, of which 19 publications were ultimately included, which covered 12 unique clinical datasets. Except for one study that investigated intravenous psilocybin, all included studies administered psilocybin orally. Psilocybin acts as a pro-drug and is rapidly absorbed and transformed to psilocin after oral administration. In the majority of studies, unconjugated psilocin was measured while some also measured conjugated and total concentrations. Psilocin's biphasic concentration-time profiles demonstrates fast and extensive disposition with an apparent distribution volume of 505-1267 L and a terminal half-life of 1.23-4.72 h. Only 1.5-3.4% of the dose is excreted as psilocin in urine. Psilocin is mainly transformed to 4-hydroxyindole-3-acetic acid and in less amounts to conjugated psilocin, where 4-hydroxyindole-3-acetic acid formation may occur prior to systemic psilocin absorption. Information on the absolute bioavailability of psilocin was limited, and estimated at 55% in one study. No covariates nor food effects have been reported, based on four studies with known fasting status.
CONCLUSIONS: Overall, we found the pharmacokinetic parameters of psilocin to be consistent between studies. This review may guide the further clinical development of psilocybin-based therapies.
Key numbers
505 to 1267 L
Volume of Distribution
Apparent volume of distribution after oral administration.
1.23 to 4.72 h
Terminal Half-Life
Range of terminal half-life for .
1.5 to 3.4%
Urinary Excretion
Percentage of dose excreted in urine.
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Declarations. Funding: No funding was received to conduct this study or prepare this article. Conflicts of Interest/Competing Interests: Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones, Michiel J. van Esdonk, Laura G.J.M. Borghans, Gabriel E. Jacobs and Coen J.G. van Hasselt have no conflicts of interest that are directly relevant to the content of this article. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Data presented in this study were acquired from authors upon request or extracted from published reports, which have been referenced. Gathered data therefore are not directly available from the authors, but may be available upon request of the referred authors. Code Availability: Code is available upon request. Authors’ Contributions: MEO and KVvH designed the study, searched, acquired and analysed the data, and drafted the manuscript. JWS designed the search strategy and searched the literature. JWS MJvE, LGJMB, GJ and JGCvH critically reviewed the manuscript. All authors read and approved the final version of the manuscript.
