Randomized, double-blind, placebo-controlled Phase II study (n=6) comparing MDMA-assisted therapy (125 mg initial + 62.5 mg supplemental per experimental session, two blinded sessions) versus placebo with therapy in adults with chronic, treatment-resistant PTSD.
This randomized, double-blind, placebo-controlled study randomizes participants to MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart; primary outcome assessed by CAPS-IV.
Each experimental session uses split dosing (125 mg MDMA HCl initial dose followed by 62.5 mg supplemental dose). Participants receive preparatory psychotherapy sessions prior to dosing and integration sessions after dosing; safety and secondary clinical measures are assessed throughout.
After unblinding, participants originally assigned to MDMA may receive an open-label third MDMA-assisted session; participants assigned to placebo may have the option to enter Stage 2 to explore titrated MDMA dosing.
MDMA-assisted therapy during two blinded experimental sessions (Stage 1); participants in MDMA arm may receive an open-label third session after unblinding.
125 mg initial followed by 62.5 mg supplemental per experimental session; two blinded sessions in Stage 1; optional open-label third session after unblinding.
Preparatory and integration psychotherapy sessions provided pre- and post-dosing.
Placebo with the same psychotherapy schedule during two blinded experimental sessions; option to enter Stage 2 after unblinding.
Placebo administered in two blinded experimental sessions.
Preparatory and integration psychotherapy sessions provided pre- and post-dosing.
Pooled analysis of six phase 2 trials found that two to three MDMA‑assisted psychotherapy sessions produced large reductions in PTSD severity at 1–2 months (LS mean change −44.8; Cohen’s d = 1.58) with further small but significant improvement at least 12 months post‑treatment (LS mean change −5.2; d = 0.23). The proportion no longer meeting PTSD criteria rose from 56% at treatment exit to 67% at long‑term follow‑up, most participants reported lasting benefits (improved relationships and well‑being) and only a minority reported harms; phase 3 trials are underway to confirm these results.