Pharmacokinetics of Psilocybin: A Systematic Review

Area of Science:

• Pharmacology
• Neuroscience
• Medicinal Chemistry

Background:

• Psilocybin demonstrates therapeutic potential for mental health disorders.
• Understanding psilocybin and psilocin pharmacokinetics is vital for clinical application and safety.

Purpose of the Study:

• To systematically review and synthesize existing research on the pharmacokinetics of psilocybin.
• To identify key pharmacokinetic parameters and metabolic pathways of psilocybin and its active metabolite, psilocin.

Main Methods:

• Systematic literature search of MEDLINE, APA PsycINFO, and Embase databases.
• Inclusion of 14 studies: 8 laboratory-based (animal/in vitro) and 6 clinical studies (112 healthy participants).
• Data extraction on absorption, distribution, metabolism, and elimination parameters.

Main Results:

• Psilocybin rapidly converts to psilocin; oral absorption Tmax: 1.8–4 h.
• Variable Cmax and bioavailability (52.7 ± 20%); extensive volume of distribution (277–1016 L).
• Metabolism primarily via CYP2D6 and CYP3A4; elimination half-life: 1.5–4 h.

Conclusions:

• Significant pharmacokinetic variability exists for psilocybin, influenced by dose, route, and species.
• CYP enzyme activity is critical for psilocybin metabolism, indicating potential drug-drug interactions.
• Further research is needed to fully elucidate the in vivo pharmacokinetic profile of psilocin.