Synthesis and In Vitro Profiling of Psilocin Derivatives: Improved Stability and Synthetic Properties
Julia Eklund, Ulf Bremberg, Jessica Larsson, Edvard Torkelsson, Johan Wennerberg, Symantha Zandelin, Luke R Odell
Journal of Medicinal Chemistry March 20, 2025 DOI: 10.1021/acs.jmedchem.4c02612 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | psilocin ester prodrugs psilocin salts |
| Topics | Psilocybin |
| Keywords | Psychedelics Drug development Pharmaceutical research Mental health treatment Medicinal chemistry |
| Citations | 4 |
| Key findings | Several psilocin ester prodrugs and psilocin salts exhibited desirable characteristics—ease of synthesis, storage and handling stability, and rapid metabolic conversion to psilocin—with potential advantages over psilocybin. |
Abstract
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability, rapid metabolic conversion to psilocin, and easy synthesis, with potential advantages over psilocybin. This research introduces viable options through psilocin ester compounds and psilocin salts, offering promising avenues for future development.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cited by 3
- Synthesis and Biological Evaluation of 4-Bromo- N,N- dimethyltryptamine (4-Br-DMT): A Synthetic Building Block for Future Analog Development ACS Omega June 23, 2026
- Psilocybin and Mental Health Outcomes: Scoping Review with ☸SAIMSARA SAIMSARA Journal June 15, 2026
- Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure Journal of Medicinal Chemistry January 26, 2026
Cites 18
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen Helvetica Chimica Acta 1959
- Investigation of the Structure–Activity Relationships of Psilocybin Analogues ACS Pharmacology & Translational Science December 14, 2020
and 13 more in the library