Pharmacokinetics • September 10, 2026
Pharmacokinetics of Psilocybin: First-Pass Metabolism, Half-Life, and Clearance
Psilocybin acts as a prodrug. Gastric and hepatic alkaline phosphatases rapidly dephosphorylate psilocybin into lipophilic active psilocin with a 2.5-hour half-life.
Psilocybin as a Pharmacologically Inactive Prodrug
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a hydrophilic zwitterion with limited direct central nervous system activity prior to enzymatic cleavage.
Enzymatic Dephosphorylation via Alkaline Phosphatase
Upon oral ingestion, intestinal and hepatic alkaline phosphatases hydrolyze the phosphate ester group, converting psilocybin into lipid-soluble psilocin (4-hydroxy-N,N-dimethyltryptamine).
Peak Plasma Concentration and Elimination Half-Life
Peak plasma levels of psilocin occur between 50 and 90 minutes post-ingestion. Psilocin exhibits an elimination half-life of roughly 160 minutes, clearing via glucuronidation in 24 hours.