MYCOLab Ai Logo - gold and army green

Pharmacokinetics of Psilocybin: A Systematic Review

Summary

This review examines how the body processes psilocybin, a compound from magic mushrooms being studied for treating depression and anxiety. When taken orally, psilocybin is quickly converted to its active form, psilocin, which reaches peak levels in the bloodstream within 1-4 hours and is eliminated mainly through urine. The body’s ability to process psilocybin involves specific liver enzymes that vary between individuals, potentially explaining why people respond differently to the same dose and why certain medications can interfere with its effects.

Background

Psilocybin, a serotonergic psychedelic, has shown promise in therapeutic applications for mental disorders. Understanding its pharmacokinetics and metabolism is crucial for optimizing clinical use and minimizing adverse effects. The role of cytochrome P450 enzymes in psilocybin metabolism may contribute to interindividual variability in drug response.

Objective

This systematic review synthesizes evidence on the pharmacokinetics of psilocybin in humans, with particular focus on the role of CYP450 enzymes in its metabolism and implications for clinical use. The review explores absorption, distribution, metabolism, and excretion of psilocybin and its active metabolite psilocin.

Results

Psilocybin is rapidly dephosphorylated to psilocin with Tmax of 1.8-4 hours following oral administration. Cmax varied dose-dependently (8.2-871 ng/mL), with bioavailability of 52.7±20%. Volume of distribution was extensive (277-1016 L), suggesting significant tissue distribution. Metabolism is mediated by CYP2D6 and CYP3A4, with secondary contributions from monoamine oxidase A. Elimination half-life ranged from 1.5-4 hours with renal excretion as primary pathway.

Conclusion

Psilocybin pharmacokinetics demonstrate significant variability based on dosage, route, and species. CYP enzymes play a critical role in metabolism, highlighting potential for drug-drug interactions. Further research is needed to elucidate psilocybin’s complete pharmacokinetic profile and optimize therapeutic use across diverse patient populations.
  • Published in:Pharmaceutics,
  • Study Type:Systematic Review,
  • Source: PMID: 40284409, DOI: 10.3390/pharmaceutics17040411
Scroll to Top