Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving MDMA and psilocybin.

Abstract

<h4>Objectives</h4>3,4-methylenedioxymethamphetamine (MDMA) and psilocybin are being investigated as potential treatments for psychiatric disorders and have received increasing regulatory and media attention due to the methodological complexities and societal context of psychedelic substances. Therefore, we assessed the consistency of protocol registration and adverse event (AE) reporting in clinical trials of MDMA and psilocybin.<h4>Study design and setting</h4>We conducted a cross-sectional analysis of all clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov by March 12, 2025. For each trial, we assessed changes to primary outcome measures (POMs) and eligibility criteria over time and evaluated whether these changes were disclosed in corresponding publications. For completed trials with both posted results and published articles, we compared AE reporting between the article and the corresponding ClinicalTrials.gov registration.<h4>Results</h4>Out of 336 trials, major changes were recorded to POMs for 17.6% trials and to eligibility criteria for 28.6% trials, most of which occurred after participant recruitment began. Among completed trials, 72.0% did not report results on ClinicalTrials.gov, and most posted results exceeded the FDAAA-recommended 1-year reporting window. Only three of 29 trials with both posted results and publications showed full concordance in AE reporting, with most exhibiting both qualitative and quantitative discrepancies.<h4>Conclusion</h4>Inconsistencies in protocol and AE reporting undermine the credibility and safety evaluation of MDMA and psilocybin trials. Greater transparency and stricter adherence to reporting standards are advised to ensure reliable evidence, protect participants, and maintain stakeholder and public trust.

Topics & conditions

Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.

Keywords