MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
How much of the benefit is the MDMA and how much is the intensive manualized therapy that came with it?
Suggestive but preliminary. Not settled. how we score evidence
Caveat on this rating: Sponsor-developer-run trial. FDA's 2024 advisory committee voted 9-2 that effectiveness was not established, citing near-total functional unblinding and allegations of trial-conduct problems in the wider program; FDA issued a CRL in Aug 2024. The paper itself is not retracted, but three related phase 2 papers are.
FDA declined approval (complete response letter, Aug 2024). NDA resubmitted Aug 2026 without a new efficacy trial; decision pending.
In 90 adults with severe PTSD (MAPP1), three MDMA-assisted therapy sessions reduced CAPS-5 scores by 24.4 points vs 13.9 with placebo plus identical therapy (d=0.91, P<0.0001) — a large effect, but delivered inside an intensive ~40-hour therapy package that placebo participants also received.
Worth asking
How much of the benefit is the MDMA and how much is the intensive manualized therapy that came with it?
Source
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study — Mitchell JM, et al. (2021)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1038/s41591-021-01336-3
DOI: 10.1038/s41591-021-01336-3
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Industry funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- 90
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- 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 "early signal". Suggestive but preliminary. Not settled. It scores 54 out of 100 on our published rubric. One caveat travels with that badge: Sponsor-developer-run trial. FDA's 2024 advisory committee voted 9-2 that effectiveness was not established, citing near-total functional unblinding and allegations of trial-conduct problems in the wider program; FDA issued a CRL in Aug 2024. The paper itself is not retracted, but three related phase 2 papers are. 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?
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study — Mitchell JM, et al. (2021). Published in: Reputable peer-reviewed journal. DOI: 10.1038/s41591-021-01336-3. 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: Randomised controlled trial. Funding: Industry funded. The researchers were not independent of whoever benefits from the result. 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.