Safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in post-traumatic stress disorder:…
Why do independent evidence graders rate this "low to very low certainty" when the raw effect sizes look so large?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: This umbrella review's STRONG tier reflects its independent, systematic method — its actual conclusion is that the underlying MDMA evidence is weak. Read the tier as confidence in the review, not in MDMA.
FDA declined approval (complete response letter, Aug 2024). NDA resubmitted Aug 2026 without a new efficacy trial; decision pending.
Across 14 systematic reviews (20 primary studies, up to 353 participants), MDMA-assisted psychotherapy showed large apparent benefits (SMD 0.8-1.3) — but the reviews that graded certainty rated the efficacy evidence low to very low because of bias risk, unblinding and imprecision, and flagged reliance on spontaneous adverse-event reporting and missing long-term safety data.
Worth asking
Why do independent evidence graders rate this "low to very low certainty" when the raw effect sizes look so large?
Source
Safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in post-traumatic stress disorder: An overview of systematic reviews and meta-analyses — Sze Jing Yong A, et al. (2025)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1177/00048674251315642
DOI: 10.1177/00048674251315642
How this was scored
- Study design
- Systematic review of randomised trials
- Funding
- Independently funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- 353
- Preregistered
- No
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "strong evidence". Well-supported by good-quality research. It scores 81 out of 100 on our published rubric. One caveat travels with that badge: This umbrella review's STRONG tier reflects its independent, systematic method — its actual conclusion is that the underlying MDMA evidence is weak. Read the tier as confidence in the review, not in MDMA. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in post-traumatic stress disorder: An overview of systematic reviews and meta-analyses — Sze Jing Yong A, et al. (2025). Published in: Reputable peer-reviewed journal. DOI: 10.1177/00048674251315642. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Systematic review of randomised trials. Funding: Independently funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is midomafetamine, mdma FDA approved for this use?
No. Its current status is: FDA approval declined. FDA declined approval (complete response letter, Aug 2024). NDA resubmitted Aug 2026 without a new efficacy trial; decision pending.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.