Synthesis and Characterization of Psilocybin Metabolites and Deuterated Analogs
Samuel E. Williamson, Elise K. Burkhartzmeyer, Michael T. Faley, Rachel Friedman Ohana, Ilia A. Guzei, Mike Valley, James J. Cali, Alexander M. Sherwood
ACS Chemical Neuroscience March 3, 2026 DOI: 10.1021/acschemneuro.5c00879 via OpenAlex
Summary
AI-generated from the abstractTo support ongoing clinical trials, the major human metabolites of psilocybin—psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA)—along with putative minor metabolites and several deuterium-labeled derivatives, were synthesized on a preparative scale. When assayed for engagement at seven serotonin receptor subtypes using a BRET-based binding assay, only psilocin exhibited any discernible binding. Given the high cost and challenging preparation of these compounds, the work provides a comprehensive guide for researchers to access these resources, advancing both basic and clinical research with psilocybin and its metabolites.
Study at a glance
| Characteristics | Preparative synthesis and in vitro binding assay Peer reviewed |
|---|---|
| Topics | Psilocybin Serotonin |
| Keywords | Hallucinogen Metabolite Biochemistry Stereochemistry |
| Key finding | Only psilocin, among psilocybin, psilocin-O-glucuronide, and 4-HIAA, showed discernible binding at seven serotonin receptor subtypes. |
Abstract
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engagement at seven serotonin receptor subtypes using a BRET-based binding assay, which showed that only psilocin exhibited any discernible binding across the subtypes investigated. Given the high cost and challenging preparation of these compounds, our work offers a comprehensive guide for researchers to access these resources, advancing both basic and clinical research with psilocybin and its metabolites.