MDMA Helps To Reduce PTSD Symptoms in Confirmatory Clinical Trial

Findings from a new confirmatory clinical trial have shown the potential for 3,4-methylenedioxymethamphetamine (MDMA) therapy in reducing post-traumatic stress disorder (PTSD) symptoms. The research, which builds upon previous studies by using a more diverse patient population, is published in Nature Medicine.

Exploring new therapies for PTSD

PTSD is a psychiatric disorder that affects 5% of the US population each year. It can arise after experiencing stressful and traumatic events, causing symptoms including flashbacks, nightmares and anxiety.

Treatments for PTSD largely consist of psychological therapies such as cognitive behavioral therapy and medications such as selective serotonin reuptake inhibitors (SSRIs). However, approximately 35–47% of patients do not respond to treatment with sertraline and paroxetine, two common SSRIs approved by the FDA to treat PTSD.

Given the complexity of the condition and the limitations of existing treatments, new therapies are needed to combat PTSD, particularly for diverse populations and racial minorities who are at a disproportionately higher risk of the disorder.

MDMA, also known as ecstasy, has shown promise in reducing the severity of PTSD symptoms in previous trials. This comes amid the growing momentum of psychedelics in clinical trials for psychiatric conditions. In the current study, researchers carried out a multi-site, confirmatory trial to evaluate the efficacy of MDMA further and investigate its effects in a more diverse patient population.

Clinically meaningful improvements

The Phase 3 randomized clinical trial aimed to test the efficacy and safety of MDMA and psychotherapy (53 patients) in comparison to placebo with psychotherapy (51 patients) for people with moderate to severe PTSD.

Of the 104 patients in the study, 28 (26.9%) identified as Hispanic/Latino and 35 (33.7%) identified as other than White.

The patients took part in three separate eight-hour dosing sessions one month apart, during which they received either MDMA or a placebo alongside therapy.

The efficacy of the treatment was measured using a scale called CAPS-5 (clinician-administered PTSD scale) used by doctors to assess the severity of PTSD symptoms.

The findings revealed that 86.5% of MDMA-treated patients experienced a clinically meaningful improvement after 18 weeks (defined as a ≥ 10-point reduction in their CAPS-5 score) compared to 69% in the placebo group.

Additionally, 71.2% of MDMA-treated patients no longer met the criteria for PTSD at the end of the study, compared to 48% of patients who received the placebo.

“This is the second Phase 3 clinical trial of MDMA therapy for severe PTSD and, similar to the previous trial, shows credible and clinically significant results suggesting that this intervention is both effective and relatively safe in this patient group,” said Dr. James Rucker, senior clinical lecturer in psychopharmacology and mood disorders at King’s College London, who was not involved in the study.

Overcoming the hurdles of psychedelic therapies

Nonetheless, while these findings provide encouraging evidence for the efficacy of MDMA therapy for PTSD, the number of patients in trials to date has not been large enough to detect the possibility of rare side effects.

“In part, this is because MDMA is classified as a Schedule 1 drug, which needlessly drives up the costs of MDMA clinical trials, which in turn reduces the number of participants that can be recruited,” explained Rucker. “The overall effect is that patients have to wait longer for new treatments based on Schedule 1 drugs to be developed.”

Prof. Neil Greenburg, a professor of defense mental health at King’s College London who was not involved in the study, also said: “This is an important trial that provides evidence of a potentially beneficial treatment option for those who cannot be helped by more traditional evidence-based treatments, which thankfully help the majority of people with PTSD to recover.”

Reference: Mitchell JM, Ot’alora GM, van der Kolk B, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023:1-8. doi: 10.1038/s41591-023-02565-4