Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans.
Nilubon Thaoboonruang, Ornrat Lohitnavy, Kimheang Ya, Manupat Lohitnavy
Scientific Reports April 21, 2025 DOI: 10.1038/s41598-025-98202-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | PBPK modeling study Peer reviewed |
|---|---|
| Population | Mice, rats, and humans |
| Intervention | psilocybin |
| Topics | Psilocybin |
| Keywords | Psilocybe cubensis Psychedelics hallucinogens Entheogens Psychoactive substances Pharmacokinetics drug metabolism Drug distribution Pbpk modeling |
| Citations | 4 |
| Key points | A PBPK model effectively characterizes psilocin disposition in mice, rats, and humans and can guide therapeutic strategies for psilocybin. |
Abstract
Psilocybin is an active alkaloid found in magic mushrooms (Psilocybe cubensis). It is classified as a Class I Psychoactive Substance due to its psychoactive properties. Recent research has suggested that psilocybin holds potential for treating major depressive disorder. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for psilocybin and its active metabolite, psilocin, in mice, rats, and humans. This model aims to explore the disposition of psilocin within the body, including its distribution to the target organ, the brain. Psilocybin is assumed to undergo complete conversion to psilocin before the latter enters systemic circulation. The PBPK model effectively characterizes the concentration-time profiles under various dosing scenarios and routes of administration in mice, rats, and humans. The human model has the potential for guiding therapeutic strategies and enhancing clinical trial designs for the therapeutic use of psilocybin.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 3
- Psychedelics and women’s mental health: the effects of female sex hormones on psychedelics’ efficacy and tolerability Molecular Psychiatry August 4, 2026
- Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure Journal of Medicinal Chemistry January 26, 2026
- Development of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model of Psilocybin/Psilocin from Psilocybe cubensis (Magic Mushroom) in Treatment-Resistant Depression. European Journal of Drug Metabolism and Pharmacokinetics August 28, 2026
Cites 26
- 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 21 more in the library