Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults
Randall Brown, Christopher R. Nicholas, Nicholas V. Cozzi, Michele Gassman, Karen M. Cooper, David W.m. Muller, Chantelle Thomas, Scott Hetzel, Kelsey M. Henriquez, Alexandra S. Ribaudo, Paul R. Hutson
Clinical Pharmacokinetics March 28, 2017 DOI: 10.1007/s40262-017-0540-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pharmacokinetic study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Healthy adults |
| Intervention | Psilocybin |
| Dose | 0.3, 0.45, and 0.6 mg/kg oral doses |
| Duration | 24-hour monitoring per dose; doses at approximately monthly intervals |
| Topics | Psilocybin |
| Keywords | Pharmacokinetics Pharmacology Urine Active metabolite Hallucinogen |
| Citations | 189 |
| Key points | Psilocin, the active metabolite of psilocybin, has a 3-hour elimination half-life and less than 2% is renally excreted intact, suggesting no dose adjustment for mild-moderate renal impairment. |
Abstract
IntroductionPsilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults.MethodsEligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods.ResultsNo psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied.ConclusionsThe small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose.Clinical trials identifierNCT02163707.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cited by 163
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports February 10, 2020
- Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Acta Psychiatrica Scandinavica October 30, 2020
- Effects of psilocybin therapy on personality structure Acta Psychiatrica Scandinavica June 19, 2018
- Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology November 1, 2020
and 158 more in the library
Cites 17
- 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
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
and 12 more in the library