This randomized, double-blind, placebo-controlled trial (n=23) assessed the safety and effectiveness of MDMA-assisted therapy (MDMA-AT) among people with chronic, treatment-resistant PTSD, including veterans.
Participants were assigned to receive either therapy with a single divided dose of MDMA or lactose placebo during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study.
During these experimental sessions, participants received an initial dose of 125 mg of MDMA followed by a supplemental dose of 62.5 mg of MDMA. Alternatively, they received initial and supplemental doses of inactive placebo.
The results (see papers below) indicate that MDMA-AT is highly effective in relieving chronic PTSD.
Country United States of America
Visit trial
Status
Completed
Results Published
Yes
Start date
01 March 2004
End date
01 September 2010
Chance of happening
100%
Phase
Phase II
Design
Blinded
Type
Interventional
Generation
First
Participants
23
Sex
All
Age
18- 70
Therapy
Yes
Trial Details
Posttraumatic stress disorder (PTSD) occurs in response to a traumatic event or events. It is most likely to occur following an event involving perceived personal threat, such as rape or physical assault. PTSD is clearly a public health problem that causes a great deal of suffering and accounts for a significant portion of health care costs. MDMA is a substance possessing unique effects that make it well suited to intensive psychotherapy. MDMA has been hypothesized to represent a new class of drugs, called entactogens, that produce feelings of closeness to others, empathy, well being, and insightfulness. Anecdotal reports of therapy conducted before MDMA was placed on Schedule I suggest that MDMA-assisted psychotherapy may benefit people with PTSD. This randomized, double-blind placebo-controlled study assessed the safety and effectiveness of MDMA-assisted therapy among people with chronic, treatment-resistant PTSD, including veterans. The study enrolled 23 participants. Participants were assigned to receive either therapy with a single divided dose of MDMA or lactose placebo during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study. During these experimental sessions, participants received an initial dose of 125 mg of MDMA followed by a supplemental dose of 62.5 mg of MDMA, or they received initial and supplemental doses of inactive placebo. Psychotherapists and independent raters were blinded to participants' treatment conditions. This treatment period also consisted of preparatory sessions and several non-drug therapy sessions to facilitate integration of material arising during experimental sessions. During Stage 2 of the study, the blind was broken and participants assigned to receive MDMA in Stage 1 underwent a third open-label experimental session of MDMA-assisted therapy. Participants assigned placebo during Stage 1 who chose to enroll in Stage 2 underwent three open-label sessions of MDMA-assisted therapy. Outcome measures were administered two months after the second MDMA or placebo session in Stage 1 and four to six weeks after the second MDMA session in Stage 2. A final data-collection session took place at two months after the third experimental session. The primary objective of the study was to measure change in PTSD symptoms via CAPS-IV across the study in participants receiving the placebo vs. full dose of MDMA-assisted psychotherapy.NCT Number NCT00090064
Sponsors & Collaborators
MAPSMAPS stands for Multidisciplinary Association for Psychedelic Studies, it's the front runner in making psychedelics a legal way to use (and improve) in therapy.
Papers
Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapyA pooled analysis of participants (n=50) in Phase II MDMA trials for PTSD found that recent tapering off SSRIs may reduce treatment response (CAPS-IV score).
Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder
This analysis of a clinical trial (n=22) examines the role of therapeutic alliance in MDMA-assisted psychotherapy (MDMA-AP) for treating chronic PTSD. It reports that after controlling for baseline PTSD severity, a strong therapeutic alliance at the mid and late stages of treatment (sessions 4 and 9) significantly predicts lower clinician-assessed and self-reported PTSD severity post-treatment.
The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study
This is the first placebo-controlled study (n=20) to shown the effectiveness of MDMA-assisted psychotherapy (MDMA-AT) in alleviating the symptoms of PTSD. Following two MDMA-AT sessions, 83% of participants in the active treatment group didn't qualify for PTSD anymore (CAPS score).
Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study
This study presents follow-up data (17-74 months; n=19) on a trial using MDMA-assisted psychotherapy to treat PTSD and found that most participants had maintained their therapeutic benefit over time.
Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials
This long-term follow-up study (n=107) examines the effects of MDMA-assisted psychotherapy on PTSD symptoms. It finds a significant reduction in PTSD symptoms both at treatment exit and at least 12 months post-treatment, with 67% of participants no longer meeting PTSD criteria at long-term follow-up.
Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline
This review (2019) details the potential superiority of MDMA-assisted psychotherapy as a treatment for PTSD compared to the conventional treatment options paroxetine and sertraline.
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
This pooled analysis (n=105; s=6) of MAPS' Phase II trials finds significant improvements (Cohen's d=0.8) and no significant adverse effects with MDMA-assisted therapy for PTSD. This analysis has been done to support starting the Phase III trials (which have taken place).
Measures Used
Clinician-Administered PTSD Scale for DSM-5The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is often considered the gold standard in PTSD assessment. The 30-item structured interview was developed by staff at the U.S. Department of Veterans Affairs National Centre for PTSD. CAPS can be used to make a current diagnosis, lifetime diagnosis or assess PTSD symptoms over the past week in accordance with DSM-5 criteria.