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Mitchell JM, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. PMID 33972795

One-paragraph summary

MAPP1 randomized 90 adults with severe PTSD to MDMA-assisted manualized therapy or the same therapy with inactive placebo after medication washout; CAPS-5 and disability were assessed two months after the final experimental session.

Key findings

  • CAPS-5 between-group standardized effect d=.91 (p<.0001).
  • Completer mean CAPS-5 change: −24.4 with MDMA versus −13.9 with placebo.
  • Sheehan Disability Scale effect d=.43 (p=.0116).

Limitations

  • Acute subjective effects threaten functional blinding.
  • The package cannot cleanly separate drug, therapy, interaction and expectancy.
  • Small phase 3 samples have limited power for rare harms; subsequent regulatory rejection is outside this paper and separately sourced.

Why it matters

This record changed the evidentiary baseline for first mdma-assisted therapy phase 3 trial; later claims should begin from this result rather than earlier narrative consensus.

Cited by wiki pages

  • mdma-and-psychedelic-assisted-therapy
  • clinical-trials-landscape
  • overview