Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy.
Archiv der Pharmazie July 1, 2025 Judith Stirn, Christian D Klein
A new chemical method enables the creation of acyloxymethyl (ACOM) prodrugs of tryptamines, including the psychedelic psilocin and the anti-migraine drug sumatriptan, by selectively protecting the indole nitrogen with a carbamate group. This approach overcomes previous chemoselectivity problems. In vitro tests show that the rate of bioactivation in human plasma can be tuned by altering the acyl residue, with half-lives up to 240 minutes. However, rapid breakdown in human saliva likely prevents sublingual or buccal delivery, though other routes like oral, transdermal, nasal, or intravenous administration remain possible.