Development of a physiologically based pharmacokinetic (PBPK) model of psilocybin and psilocin from magic mushroom in rats and humans

Abstract

Background : Psilocybin (PB) is a psychoactive compound commonly found in magic mushroom ( Psilocybe cubensis ) . PB is quickly converted by the body to psilocin (PI), which has a psychedelic effect through the activation of the 5 - HT 2A receptor in the brain. The objective of this study is to develop a physiologically based pharmacokinetic (PBPK) model of PB and PI in rats and humans for predicting concentrations of the psychoactive substance in the brain. Methods : Following a search in PubMed, three studies were retrieved and information concerning concentration - time profiles of PI were extracted from the selected studies. In the study in rats, PI was orally administered with a dose of 10.1 mg / kg. There were two studies in humans following a single intravenous dose of PB (1 mg) and oral dose of PB (0.224 mg / kg and 0.3 mg / kg). Berkeley Madonna software was used for computer coding and simulations. The developed PBPK model consisted of seven organ compartments (i.e. lung, heart, brain, fat, muscle, kidney, and liver). Results : The simulations show a good agreement between observed and simulated data, although results for oral administration in rats and humans showed under - predictions and results for intravenous administration in humans showed over - predictions. Conclusions : A PBPK model of PB and PI in rats and humans was developed and could predict concentration-time profiles of PI in plasma, particularly in the brain, following intravenous and oral administration of PB. This model may be useful for a safer dosage regimen of PB for patients with some disorders.