RETRACTED ARTICLE: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials

Summary & key facts

This paper pooled data from six randomized, double‑blind phase‑2 trials of MDMA‑assisted psychotherapy for adults with PTSD (total N=103). After two blinded MDMA sessions, the MDMA group showed larger reductions in clinician‑rated PTSD symptoms than the control group (mean difference −22.0 points on the CAPS‑IV, P < 0.001) and a large effect size (Cohen’s d = 0.8). More people in the MDMA group no longer met PTSD diagnostic criteria after two sessions (54.2% vs 22.6%). The authors reported the treatment was generally well tolerated and noted improvement in depressive symptoms that trended toward significance. Important: this article has been formally retracted (Psychopharmacology 2024 Aug 10

Key facts:

• The pooled dataset included 103 participants: 72 received active MDMA doses (75–125 mg) and 31 received placebo or low/control doses (0–40 mg).
• After two blinded experimental sessions, the MDMA group had a between‑group MMRM estimated mean difference on CAPS‑IV total scores of −22.0 (SE 5.17), P < 0.001, favoring MDMA‑assisted psychotherapy.
• The between‑group Cohen’s d effect size for PTSD symptom change after two sessions was 0.8, which is commonly interpreted as a large effect.
• After two experimental sessions, 54.2% of participants in the active MDMA group did not meet CAPS‑IV PTSD diagnostic criteria, compared with 22.6% in the control group.
• Depression symptoms measured by the BDI‑II improved more in the MDMA group with an estimated mean difference of −6.0 (SE 3.03), which trended toward but did not reach conventional significance (P = 0.053).
• All MDMA dose levels used in these phase‑2 trials were reported as generally well tolerated, though some expected acute reactions occurred more often in the MDMA group during sessions and in the following 7 days.
• The six randomized, double‑blind trials were conducted at five sites from April 2004 to March 2017 and were designed to inform phase‑3 trial planning.
• This article has been retracted by the journal (see Psychopharmacology 2024 Aug 10;241(11):2405); readers should treat the reported findings in the paper in that context.

Abstract

ClinicalTrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

Topics

Cannabis and Cannabinoid Research Posttraumatic Stress Disorder Research Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Clinical psychology Internal medicine MDMA Medicine Psychiatry Psychology Psychotherapist Randomized controlled trial Research design Social science Sociology

Substances

MDMA

Conditions & symptoms

Depression PTSD Anxiety or worry Sadness or low mood