Phase III MDMA-Assisted Therapy Shows Significant PTSD Symptom Reduction
A confirmatory phase III trial demonstrated that MDMA-assisted therapy significantly reduced PTSD symptoms compared to placebo with therapy, with a large effect size (d=0.7) and manageable safety. While outside traditional diagnostic lab scope, the trial highlights emerging needs for therapeutic drug monitoring and pharmacogenomic testing as psychedelic-assisted therapies approach clinical adoption.
The original study
MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.
- Authors
- Mitchell JM, Ot'alora G M, van der Kolk B, Shannon S, Bogenschutz M, Gelfand Y, et al.
- Journal
- Nature medicine
- Type
- Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 37709999
Original abstract
This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .