Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans.

A physiologically based pharmacokinetic (PBPK) model was developed to describe how psilocybin and its active metabolite psilocin distribute through the body in mice, rats, and humans. Psilocybin is assumed to convert completely to psilocin before entering systemic circulation. The model accurately characterizes concentration-time profiles across different doses and routes of administration. It can help guide therapeutic strategies and improve clinical trial designs for using psilocybin to treat major depressive disorder.

Study at a glance

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.