MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial
Given FDA declined approval on this evidence in 2024, what additional data would change that judgment — and does the 2026 resubmission actually contain it?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Same sponsor-developer structure and unblinding problem as MAPP1; FDA's CRL asked for a further trial, which the Aug 2026 resubmission does not include (it relies on an audit, a phase 1 cardiac study and VA follow-up data instead).
FDA declined approval (complete response letter, Aug 2024). NDA resubmitted Aug 2026 without a new efficacy trial; decision pending.
In 104 adults with moderate-to-severe PTSD (MAPP2; 53 MDMA-AT, 51 placebo with therapy), CAPS-5 improved 23.7 vs 14.8 points (d=0.7, P<0.001) — a smaller effect than MAPP1, again confounded by intensive adjunctive therapy and probable unblinding.
Worth asking
Given FDA declined approval on this evidence in 2024, what additional data would change that judgment — and does the 2026 resubmission actually contain it?
Source
MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial — Mitchell JM, et al. (2023)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1038/s41591-023-02565-4
DOI: 10.1038/s41591-023-02565-4
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Industry funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- 104
- 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 "moderate evidence". Reasonable evidence with real limitations. It scores 56 out of 100 on our published rubric. One caveat travels with that badge: Same sponsor-developer structure and unblinding problem as MAPP1; FDA's CRL asked for a further trial, which the Aug 2026 resubmission does not include (it relies on an audit, a phase 1 cardiac study and VA follow-up data instead). 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 moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial — Mitchell JM, et al. (2023). Published in: Reputable peer-reviewed journal. DOI: 10.1038/s41591-023-02565-4. 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.