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

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 thi...

Full description

Saved in:
Bibliographic Details
Main Authors: Nilubon Thaoboonruang, Ornrat Lohitnavy, Kimheang Ya, Manupat Lohitnavy
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-98202-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849713517164232704
author Nilubon Thaoboonruang
Ornrat Lohitnavy
Kimheang Ya
Manupat Lohitnavy
author_facet Nilubon Thaoboonruang
Ornrat Lohitnavy
Kimheang Ya
Manupat Lohitnavy
author_sort Nilubon Thaoboonruang
collection DOAJ
description 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.
format Article
id doaj-art-22d9724246e54697bf35e135a684d813
institution DOAJ
issn 2045-2322
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-22d9724246e54697bf35e135a684d8132025-08-20T03:13:57ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-98202-wDevelopment of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humansNilubon Thaoboonruang0Ornrat Lohitnavy1Kimheang Ya2Manupat Lohitnavy3Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan UniversityCenter of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan UniversityCenter of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan UniversityCenter of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan UniversityAbstract 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.https://doi.org/10.1038/s41598-025-98202-wMagic mushroomsPsilocybe cubensisPsilocybinPsilocinPBPK
spellingShingle Nilubon Thaoboonruang
Ornrat Lohitnavy
Kimheang Ya
Manupat Lohitnavy
Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
Scientific Reports
Magic mushrooms
Psilocybe cubensis
Psilocybin
Psilocin
PBPK
title Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
title_full Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
title_fullStr Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
title_full_unstemmed Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
title_short Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans
title_sort development of a pbpk model of psilocybin psilocin from psilocybe cubensis magic mushroom in mice rats and humans
topic Magic mushrooms
Psilocybe cubensis
Psilocybin
Psilocin
PBPK
url https://doi.org/10.1038/s41598-025-98202-w
work_keys_str_mv AT nilubonthaoboonruang developmentofapbpkmodelofpsilocybinpsilocinfrompsilocybecubensismagicmushroominmiceratsandhumans
AT ornratlohitnavy developmentofapbpkmodelofpsilocybinpsilocinfrompsilocybecubensismagicmushroominmiceratsandhumans
AT kimheangya developmentofapbpkmodelofpsilocybinpsilocinfrompsilocybecubensismagicmushroominmiceratsandhumans
AT manupatlohitnavy developmentofapbpkmodelofpsilocybinpsilocinfrompsilocybecubensismagicmushroominmiceratsandhumans