Phase 3 Trial of MDMA Therapy for PTSD Finds Excellent Results, Safety Record

A phase 3 clinical trial of methylenedioxymethamphetamine (MDMA)-assisted therapy for patients with severe, chronic post-traumatic stress disorder (PTSD) has found that the drug is an effective treatment, with more than half of the participants who received MDMA no longer qualifying for a PTSD diagnosis.

MDMA is currently listed as a Schedule I drug and is defined as having no medical benefit, making it inaccessible as a treatment except when administered in clinical trials. In a press release, however, Multidisciplinary Association for Psychedelic Studies (MAPS) Executive Director Rick Doblin, PhD, said that the drug has the potential to change the entire therapeutic process and generate positive outcomes.

These results replicated and expanded on phase 2 trial results from MAPS, which found that MDMA-assisted therapy might be an effective and cost-saving treatment for PTSD. According to the press release, their new findings represent the first phase 3 trial of any psychedelic-assisted therapy.

“The experience of having been traumatized profoundly alters perceptions; self-experience; and capacity to plan, imaging, and anticipate,” said principal investigator for the Boston study site, Bessel van der Kolk, MD, in the press release. “For 88% of people who receive this treatment, we can expect to see a treatment response. This can lead to fundamental shifts in our subjects’ perspective on self-capacity, affect regulation, and attitude toward those around them.”

The randomized, blinded, phase 3 trial was designed under a Special Protocol Assessment with the FDA. It involved 90 patients with severe, chronic PTSD who were randomized to receive 3 sessions of either MDMA or placebo with identical talk therapy. Forty-six patients received MDMA therapy and 44 received therapy with placebo.

The primary efficacy endpoint was based on the change from baseline in a clinical interview of PTSD severity after 18 weeks. Investigators also examined average change in functional impairment in work or school, social, and family life.

In the trial, participants who received MDMA-assisted therapy reported a significant reduction in PTSD symptoms compared to patients who received placebo with therapy. Participants in the MDMA-arm successfully achieved the primary endpoint for the trial, with 67% no longer qualifying for a PTSD diagnosis after 3 treatment sessions, compared to 32% in the control arm.

Furthermore, patients treated with MDMA-assisted therapy had statistically significant reductions for the key secondary endpoint of functional impairment relative to placebo with therapy.

“People with the most difficult-to-treat diagnoses, often considered intractable, respond just as well to this novel treatment as other study participants,” said Jennifer Mitchell, PhD, lead author of the paper, in the press release. “In fact, participants diagnosed with the dissociative subtype of PTSD experienced a greater reduction in symptoms than those without the dissociative subtype.”

The investigators observed no serious safety or tolerability issues in the MDMA group. It did not increase the risk of suicidal thoughts or behaviors and did not increase cardiovascular risk or abuse potential relative to therapy with a placebo.

As expected, based on earlier clinical trials, temporary increases in blood pressure and pulse were observed during the treatment sessions with MDMA, whereas adverse events such as muscle tightness, decreased appetite, nausea, sweating, and feeling cold were transient.

“It takes a great deal of courage to address one’s PTSD, particularly when other treatments have failed,” van der Kolk said in the press release. “These results open the door to a potentially powerful new pathway to healing—once MDMA-assisted therapy has been approved as a treatment for PTSD.”

REFERENCE

MAPS’ Phase 3 Trial of MDMA-Assisted Therapy for PTSD Achieves Successful Results for Patients with Severe, Chronic PTSD [news release]. MAPS; May 3, 2021. https://maps.org/news/media/9122-maps-phase-3-trial-of-mdma-assisted-therapy-for-ptsd-achieves-successful-results-for-patients-with-severe-chronic-ptsd. Accessed May 4, 2021.