In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin
Frontiers in Psychiatry January 8, 2024 N. Jones, Laura M. Wagner, Molly C. Pellitteri Hahn et al. 10 citations
Psilocybin, a psychedelic compound used in psychotherapy research, is converted in the body to the active metabolite psilocin. Psilacetin (4-AcO-DMT) has long been thought to be an alternative prodrug for psilocin, but direct evidence was lacking. In mice, psilocybin produced 10–25% higher psilocin concentrations than psilacetin at 15 minutes after injection. The half-life of psilocin was about 30 minutes from either prodrug. Overall, psilacetin fumarate yielded about 70% of the psilocin exposure that psilocybin did. These results confirm that psilacetin acts as a psilocin prodrug in vivo and suggest it can be used as a substitute for psilocybin in mechanistic research with mice.