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

A cross-sectional analysis of 336 clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov found that 17.6% made major changes to primary outcome measures and 28.6% changed eligibility criteria, most after recruitment began. Among completed trials, 72.0% did not post results on the registry, and most that did exceeded the one-year reporting window. Only 3 of 29 trials with both posted results and publications had fully concordant adverse event reporting; most showed qualitative and quantitative discrepancies. These inconsistencies undermine the credibility and safety evaluation of these trials, and the authors advise greater transparency and stricter adherence to reporting standards.

Study at a glance

Abstract

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. 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. 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 one-year reporting window. Only 3 of 29 trials with both posted results and publications showed full concordance in AE reporting, with most exhibiting both qualitative and quantitative discrepancies. Inconsistencies in protocol and adverse event 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.