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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preparative synthesis and in vitro binding assay Peer reviewed |
|---|---|
| Topics | Psilocybin Serotonin |
| Keywords | Hallucinogen Metabolite Biochemistry Stereochemistry Binding site Plasma protein binding Pharmacology In vitro Receptor |
| Key points | 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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cites 22
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Single-Dose Psilocybin Treatment for Major Depressive Disorder JAMA August 31, 2023
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine February 1, 2023
and 17 more in the library