Development of a physiologically based pharmacokinetic (PBPK) model of psilocybin and psilocin from magic mushroom in rats and humans
Prinya Musikaphongsakul, Kimheang Ya, Pakpoom Subsoontorn, Manupat Lohitnavy
F1000Research March 15, 2021 DOI: 10.12688/f1000research.28133.1 via OpenAlex
Summary
AI-generated from the abstractA physiologically based pharmacokinetic model predicts concentrations of psilocin, the active metabolite of psilocybin, in plasma and brain after intravenous and oral administration in rats and humans. The model, built from three published studies, uses seven organ compartments and shows good overall agreement with observed data, though oral doses are under-predicted and intravenous doses over-predicted. This tool may help design safer dosing regimens for therapeutic use.
Study at a glance
| Characteristics | Physiologically based pharmacokinetic modeling Peer reviewed |
|---|---|
| Population | Rats and humans |
| Intervention | Psilocybin |
| Dose | 10.1 mg/kg (rats, oral); 1 mg (humans, intravenous); 0.224 mg/kg and 0.3 mg/kg (humans, oral) |
| Keywords | Pharmacology Ns3 Pharmacokinetics Chemistry Medicine |
| Citations | 6 |
| Key finding | A PBPK model of psilocybin and psilocin in rats and humans predicts concentration-time profiles of psilocin in plasma and brain with acceptable accuracy, though oral administrations are under-predicted and intravenous administrations over-predicted. |
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-HT2A 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.