Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving MDMA and psilocybin.
Marija Franka Žuljević, Antonija Mijatović, Renata Orhanović, Glenn Goasdoué, Diana Gujinović
Journal of Clinical Epidemiology January 23, 2026 DOI: 10.1016/j.jclinepi.2026.112170 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional analysis Qualitative Peer reviewed |
|---|---|
| Sample size | 336 |
| Population | Clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov |
| Topics | MDMA Psilocybin |
| Keywords | Clinicaltrials.gov Adverse events Pre-registration Psychedelics Reporting |
| Citations | 4 |
| Key findings | Inconsistencies in protocol registration and adverse event reporting are widespread in MDMA and psilocybin clinical trials, with most completed trials failing to report results on time and few showing full concordance in adverse event reporting between registry and publications. |
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.
Comparable studies
Other cross-sectional and survey studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug Recreational Ecstasy users recruited via snowball peer network | 1992 | Cross-sectional survey | n = 100 |
| Reducedin vivobinding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users Male regular ecstasy users and well-matched controls | 1999 | Cross-sectional association study | n = 20 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Patterns of recreational drug use at dance events in Edinburgh, Scotland Drug users at dance events in Edinburgh, Scotland, UK, aged 16-47, 80% between 18 and... | 2001 | Cross-sectional survey | n = 122 |
| Acute, sub‐acute and long‐term subjective consequences of ‘ecstasy’ (MDMA) consumption in 430 regular users Regular MDMA users | 2003 | Cross-sectional study | n = 466 |
Citations in the library
Cited by 3
- Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review. Clinical Pharmacology & Therapeutics July 1, 2026
- Lived experience as systems-relevant evidence in psychedelic public health Frontiers in Public Health September 15, 2026
- Methodological fragmentation and integration priorities in psychedelic-assisted therapy assessment: a scoping review Frontiers in Psychiatry August 6, 2026
Cites 17
- Global Street Food: la cocina de la calle Diseño interior 2009
- Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials Psychopharmacology April 1, 2022
- Preparing for the Bursting of the Psychedelic Hype Bubble. JAMA Psychiatry October 1, 2022
- A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses Journal of the Neurological Sciences January 31, 2020
- The 21st century psychedelic renaissance: heroic steps forward on the back of an elephant Psychopharmacology August 23, 2017
and 12 more in the library