MDMA-assisted psychotherapy proved safe and effective in treating post-traumatic stress disorder (PTSD) symptoms in a diverse patient population, according to findings from the phase III randomized MAPP2 trial.
Based on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score, patients undergoing MDMA-assisted psychotherapy saw a significant improvement in their symptoms compared with those who received placebo with psychotherapy (least squares mean change -23.7 vs -14.8; P<0.001), reported Jennifer M. Mitchell, PhD, of the University of California San Francisco, and colleagues.
There was also an improvement in clinician-rated functional impairment, measured by the Sheehan Disability Scale, with MDMA-assisted therapy versus placebo with therapy (least squares mean change -3.3 vs -2.1, P=0.03), they noted in Nature Medicine.
These results supported earlier findings that MDMA-assisted therapy was effective for improving PTSD symptoms, though Mitchell said another important aspect of this trial that set it apart from earlier research was its diverse patient population.
Previous trials failed to account for the needs of a diverse patient population, she noted, especially among more marginalized groups. Some trials had to turn away certain patients who needed more support to be enrolled in the trial, such as transportation or child care, because the researchers didn’t have the means to support those patients. This limitation led to a less diverse, more affluent group of participants, according to Mitchell.
However, for this trial, the researchers were given the resources to include patients from all backgrounds, which allowed for a more diverse and robust study.
“The results continued to hold in populations that perhaps were more marginalized,” Mitchell said. “This population, I believe, more likely represents the general population with PTSD, which means that these results should be more indicative of what we would see if MDMA-assisted therapy were FDA approved.”
“There aren’t drugs to specifically treat PTSD. We only have two FDA-approved compounds for the treatment of PTSD, and they’re both SSRIs [selective serotonin reuptake inhibitors] … to mitigate those signs and symptoms of depression,” she added. “This is different. This actually affects PTSD, and it doesn’t just sort of address the symptoms, it appears to address the cause.”
In 2017, the FDA granted a Breakthrough Therapy Designation for the use of MDMA-assisted therapy to treat PTSD when administered as an adjunct treatment to psychotherapy, and Mitchell said that these data should provide the basis to submit a new drug application for MDMA-assisted therapy, though she noted that there is still more research to be done.
“The next big question, of course, is how durable are the effects of these compounds,” she noted.
“The hope is that MDMA and psychedelics in general might have a signal in not just PTSD and depression … but in other mental health disorders as well,” she added. “The objective will be to evaluate all of the psychedelics in each of these different disorders to determine how far the therapeutic efficacy reaches.”
For this double-blind, confirmatory trial conducted at 13 sites, Mitchell and team enrolled 104 adults: 26.9% had moderate PTSD and 73.1% had severe PTSD. Participants were randomized to MDMA-assisted therapy (n=53; mean age 38) or placebo (n=51; mean age 40).
Therapy was conducted by trained personnel in accordance with the MAPS MDMA-assisted treatment manual and trial protocol.
About 34% of participants identified their race as other than white, with 26.9% of participants identifying as Hispanic or Latino. In total, 71.2% were assigned female sex at birth, with a higher proportion in the placebo group (82.4%) versus the MDMA-assisted group (60.4%). The mean duration of PTSD was 16.2 years, and the mean CAPS-5 score at baseline was 39.0 and was similar between groups.
Seven participants experienced severe treatment-emergent adverse events (TEAEs); five participants in the MDMA-assisted therapy group and two in the placebo group. No deaths or serious TEAEs were reported.
The trial was supported by the Multidisciplinary Association for Psychedelic Studies (MAPS) with support from the Steven and Alexandra Cohen Foundation.
Mitchell has received grants/contracts from the Veterans Administration and the FDA; royalties/licenses from UCLA (for a patent licensed to UCSF); payment/honoraria from Stanford University and Johns Hopkins; and has been a reviewer for the National Institute on Alcohol Abuse and Alcoholism Clinical Trials Network and the Australian Medical Research Council.
Co-authors disclosed multiple relationships with industry and nonprofit organizations.
Source Reference: Mitchell JM, et al “MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial” Nat Med 2023; DOI: 10.1038/s41591-023-02565-4.