Pooled review of 30 trials of MDMA and psychedelics for mental disorders

The question

How well do MDMA and serotonergic psychedelics (such as psilocybin, LSD and ayahuasca) work for mental disorders, how many people drop out, and how certain is the evidence?

What they did

Researchers searched medical databases and trial registries up to 8 July 2025 for double-blind randomized controlled trials testing MDMA or serotonergic psychedelics in people diagnosed with a mental disorder. They pooled results across studies and rated both the risk of bias in each trial and the overall certainty of the evidence. The review is kept as a “living” review, meaning it is updated as new trials appear. They included 30 trials with 1,480 participants; 45.8% were female, 83.3% of trials included psychological support, and 83.3% were rated at high risk of bias.

What they found

For post-traumatic stress disorder, MDMA reduced symptoms compared with any control (11 trials; standardized mean difference -0.85, a large effect; certainty rated low). For major depressive disorder, psilocybin, ayahuasca or LSD reduced depressive symptoms (8 trials; SMD -0.62; very low certainty). In anxiety disorders, both MDMA (2 trials; SMD -1.18) and serotonergic psychedelics (5 trials; SMD -0.88) reduced anxiety symptoms, at low and very low certainty. Neither psilocybin nor LSD improved abstinence rates in alcohol use disorder (6 trials; relative risk 1.42, range 0.89 to 2.26), and a single LSD trial did not reduce ADHD symptoms (SMD 0.22). Dropout for any reason was not higher than with control, and only MDMA for PTSD versus placebo reached moderate certainty.

The fine print

Most of the included trials (83.3%) were rated at high risk of bias, and the authors note that participants can often tell whether they received an active drug, which can inflate apparent benefits. Several comparisons rest on very few trials, and results for depression and anxiety varied notably between studies. Follow-up in the source trials was largely short-term, and most involved psychological support alongside the drug, so the drug’s effect alone cannot be separated. This summary is based on the abstract only.

What it means

Pooled trial evidence suggests MDMA and serotonergic psychedelics can reduce symptoms of PTSD, depression and anxiety, with no sign of higher dropout, but the certainty of that evidence is mostly low because of study quality and blinding problems, and the alcohol and ADHD results were null.

Evidence grade: Moderate. A meta-analysis limited to double-blind randomized trials, but most included trials were judged to be at high risk of bias and the certainty of most results was rated low or very low.

This summary is based on the study’s published abstract.