Combination of psychedelic drug, psychotherapy improves PTSD symptoms

The combination of MDMA and psychotherapy improved PTSD symptoms among participants in a phase 3 clinical trial, researchers reported at the spring meeting of the American Chemical Society.

Preliminary findings suggest that the combination works in hard-to-treat patients, including those with drug or alcohol use disorders, Jennifer Mitchell, PhD, principal investigator and professor of neurology at the University of California, San Francisco, and colleagues report.

According to Mitchell, the use of psychedelic drugs to treat these disorders is not new, and some psychiatrists used MDMA to enhance psychotherapy as early as the 1970s.

“MDMA is really interesting because it’s an empathogen,” Mitchell said in a press release. “It causes the release of oxytocin in the brain, which creates feelings of trust and closeness that can really help in a therapeutic setting.”

Because selective serotonin reuptake inhibitors (SSRIs), which are first-line therapeutics for PTSD patients, are effective in just about half of patients, Mitchell and colleagues explored the use of MDMA to improve psychotherapy by enrolling 90 participants with severe PTSD in a phase 3, randomized, double-blind, placebo-controlled study.

In previous phase 2 studies, investigators had determined the optimal oral dosage of MDMA was a full dose, followed by a half dose an hour later. In this phase 3 trial, participants attended an 8-hour therapy session after receiving the half dose. This process was repeated twice, a month apart each time, in addition to weekly therapy.

Mitchell and colleagues assessed change in PTSD symptoms (CAPS-5) and functional impairment (SDS) by a central, blinded independent rater pool at baseline and following each treatment. Participants also were monitored for adverse events during the study.

According to the release, MDMA in combination with psychotherapy significantly reduced CAPS-5 scores (n = 89; d = 0.91; 95% CI, 0.44-1.37; P < .0001) and SDS scores (d = 0.43; 95% CI, –0.01 to 0.88; P = .0116). The mean change in CAPS-5 scores was –24.4 among 42 participants in the MDMA/therapy group and –13.9 among 37 in the placebo/therapy group.

“The effect size for MDMA-assisted therapy is better than that for the SSRIs that have been investigated, suggesting that MDMA is a far better therapeutic for PTSD,” Mitchell said.

Mitchell and colleagues are currently enrolling participants for a second phase 3 trial. They anticipate that MDMA-assisted therapy for PTSD could potentially receive FDA approval as early as 2023.