Abstract
Introduction
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.
Methods
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.
Results
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.
Discussion
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.
Keywords
psilocybin - regulatory compliance - major depressive disorder - treatment-resistant
depression
