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Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants

Friederike Holze, Urs Duthaler, Anna M Becker, Karolina E. Kolaczynska, Matthias E. Liechti

Clinical Pharmacology & Therapeutics December 12, 2022 DOI: 10.1002/cpt.2821 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Pharmacokinetic-pharmacodynamic study Peer reviewed
Sample size 28
Population Healthy subjects
Intervention Psilocybin
Dose 15, 25, and 30 mg
Duration Up to 24 hours
Topics Psilocybin
Keywords Pharmacology Pharmacokinetics Pharmacodynamics Hallucinogen Metabolite Dosing Oral administration Confidence interval
Citations 116
Key points Psilocin exhibited dose-proportional pharmacokinetics, and the duration and intensity of subjective effects were dose-dependent, with body weight not influencing pharmacokinetics or response.

Abstract

Psilocybin is being investigated as a potential treatment for psychiatric and neurological disorders. Only a few studies have evaluated the pharmacokinetics (PKs) of psilocybin and have used body weight‐adjusted dosing. Data on PKs and the PK‐pharmacodynamic (PD) relationship of fixed doses that are commonly used are unavailable. The present study characterized the PKs and PK‐PD relationship of 15, 25, and 30 mg of orally administered psilocybin in 28, 23, and 28 healthy subjects, respectively. Plasma levels of unconjugated psilocin (the psychoactive metabolite of psilocybin) and corresponding subjective effects were repeatedly assessed up to 24 hours. PK parameters were determined using compartmental modeling. Concentration‐subjective effect relationships were described using PK‐PD modeling. Mean (95% confidence interval) maximal psilocin concentrations were 11 ng/mL (10‐13), 17 ng/mL (16‐19), and 21 ng/mL (19‐24) after the administration of 15, 25, and 30 mg psilocybin, respectively. Maximal concentrations were reached after an average of 2 hours. Elimination half‐lives were 1.8 hours (1.7–2.0), 1.4 hours (1.2–1.7), and 1.8 hours (1.6–1.9) for 15, 25, and 30 mg psilocybin, respectively. Mean (± SD) durations of subjective effects were 5.6 ± 2.2 hours, 5.5 ± 1.6 hours, and 6.4 ± 2.2 hours, and maximal effects (“any drug” effects) were 58% ± 25%, 73% ± 27%, and 80% ± 18% after 15, 25, and 30 mg psilocybin, respectively. Psilocin exhibited dose‐proportional PKs. The duration and intensity of subjective effects were dose‐dependent. Body weight did not influence pharmacokinetics or the response to psilocybin. These data may serve as a reference for future clinical trials.

Comparable studies

Other experimental studies on psilocybin, most cited first.

Study Year Design Participants
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers 1998 Experimental study
Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... 2015 Validation study using pooled data from five laboratory experiments n = 184
Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants 2013 Experimental study
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... 2020 Long-term within-subjects follow-up analysis n = 15
Enzymatic Synthesis of Psilocybin 2017 Laboratory study

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