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.
A transdermal patch for delivering N,N-dimethyltryptamine (DMT) at low, non-hallucinogenic doses was developed and tested in mice. The patch provided consistent, extended drug release, achieving plasma levels below 60 ng/mL. Compared to intravenous administration, the patch extended DMT's half-life by 20-fold and achieved 77% bioavailability. Female and male mice showed notable differences during IV dosing, but transdermal delivery produced steady levels. A head twitch assay indicated no hallucinogenic effects at these low plasma concentrations. The patch could offer a non-invasive, outpatient treatment option for conditions where high, bolus doses are unnecessary.