Regulatory Alignment of Psilocybin Clinical Trials in Major Depressive Disorder on ClinicalTrials.gov: A Cross-Sectional Analysis
Aleksander Kwaśny, Zuzanna Gaca, Damian Swieczkowski, Michal Pruc, Lukasz Szarpak, Wiesław Jerzy Cubała
Pharmacopsychiatry April 17, 2025 DOI: 10.1055/a-2529-7029 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional investigation Double-blind Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Clinical trial protocols for psilocybin in major depressive disorder and treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Topics | Depression Psilocybin |
| Keywords | Clinical trial Expectancy theory Schizoaffective disorder |
| Citations | 2 |
| Key findings | Psilocybin trial protocols for MDD and TRD show gaps in regulatory compliance, particularly regarding drug interactions, concurrent antidepressant use, and management of functional unblinding and expectancy bias. |
Abstract
Abstract Regulatory compliance is crucial in the clinical development of psychedelic substances, including psilocybin. This study aimed to examine the alignment of clinical trial protocols for psilocybin in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD) with established regulatory requirements. A cross-sectional investigation was conducted on ClinicalTrials.gov using the keywords: “Psilocybin” and “Psilocin” to identify interventional studies with posted trial protocols. Only protocols for MDD and TRD were included. Data extraction focused on key regulatory aspects, including safety, functional unblinding, expectancy bias, and the distribution of investigational medical products. Eleven psilocybin trial protocols were identified, with four meeting the inclusion criteria. The most commonly studied psilocybin dose was 25 mg. Two trials were double-blind. Although the analyzed protocols superficially adhered to regulatory requirements, there were gaps in addressing potential drug interactions, the acute and chronic concurrent use of antidepressants, and prohibited medications. Certain aspects, such as functional unblinding or expectancy bias, did not share all pathways. Risk mitigation strategies were primarily based on external criteria. Patients with bipolar spectrum disorders or schizoaffective disorders were excluded. This study underscores the importance of conducting clinical trials on psychedelics in strict adherence to regulatory standards. Future research should focus on improving regulatory compliance and exploring the efficacy of psychedelics in broader patient populations.
Comparable studies
Other cross-sectional and survey studies on psilocybin for depression, most cited first.
Citations in the library
Cited by 3
- Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols. European Neuropsychopharmacology January 16, 2026
- Beyond Efficacy Signals: Regulatory, Methodological, and Translational Challenges in Clinical Research on Ketamine and Psilocybin in Psychiatry Psychiatry International September 1, 2026
- Psychedelic-assisted pharmacotherapy: clinical applications and regulatory considerations Expert Opinion on Pharmacotherapy March 24, 2026
Cites 32
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- Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up Journal of Psychopharmacology February 1, 2022
- Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review Frontiers in Psychiatry July 12, 2022
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- Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. Current Drug Abuse Reviews 2014
and 27 more in the library