MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

Summary & key facts

This was a carefully controlled trial that tested therapy plus MDMA against the same therapy with a placebo in about 100 people who had moderate to severe post-traumatic stress disorder. People who received MDMA with therapy showed a bigger drop in PTSD symptoms and a greater improvement in daily functioning than people who got placebo and therapy. The treatment was generally tolerated but a few people had serious side effects. These results are promising but come from one study with about 100 people, so more research is needed to know how well this would work for others and over longer times.

Key facts:

• The study randomly assigned 104 people with moderate to severe PTSD to two groups. One group of 53 people got MDMA-assisted therapy and the other group of 51 people got placebo with the same therapy.
• About 27 percent of participants had moderate PTSD and about 73 percent had severe PTSD when the study started.
• Researchers measured change in PTSD symptoms using a standard clinician-rated score. On average the PTSD symptom score dropped by about 24 points with MDMA-assisted therapy and by about 15 points with placebo plus therapy.
• Researchers also measured how much PTSD interfered with daily life. That score improved by about 3 points with MDMA-assisted therapy and by about 2 points with placebo plus therapy.
• The difference in symptom drop was judged unlikely to be due to chance and represents a moderate-sized advantage for the MDMA group. The improvement in daily function showed a smaller but still noticeable advantage for the MDMA group.
• Seven people experienced a severe treatment-related side effect. Five of those people were in the MDMA group and two were in the placebo group. There were no deaths and no events judged to be serious by the study.
• The study included people from diverse racial and ethnic backgrounds. About 27 percent identified as Hispanic or Latino and about 34 percent identified as races or ethnicities other than White.
• These results suggest MDMA with therapy reduced PTSD symptoms more than the same therapy with placebo in this trial, but this is one trial with about 100 people so we cannot assume the same results will apply to everyone or over longer periods.

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 .

Topics

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Tryptophan and brain disorders

Categories

Clinical Psychology Psychology Social Sciences

Tags

Alternative medicine Internal medicine MDMA Medicine Pathology Placebo Psychiatry Randomized controlled trial

Substances

MDMA

Conditions & symptoms

PTSD Substance abuse disorder Anxiety or worry Feeling disconnected from others Poor sleep