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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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) |
| Topics | Psilocybin |
| Keywords | Pharmacology Ns3 Pharmacokinetics |
| Citations | 6 |
| Key points | 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.