A new study has found that combining the drug MDMA with psychotherapy can help people with moderate to severe post-traumatic stress disorder (PTSD) reduce their symptoms and improve their ability to perform everyday activities. The research, which was conducted as a double-blinded randomized clinical trial, was published in Nature Medicine.
PTSD is a serious mental health condition that affects individuals who have experienced or witnessed a traumatic event, such as violence or natural disasters. Individuals with PTSD may have nightmares, flashbacks, anxiety, depression and difficulty functioning in daily life. Current treatments include psychotherapies (talking therapies that assist people explore their inner thoughts and feelings) in addition to medications, but they have been found to not work for all.
Growing evidence suggests a compound called 3,4-methylenedioxymethamphetamine (more commonly known as MDMA, ecstasy or molly) as a potential treatment. MDMA is a substance that can reduce fear as well as enhance empathy and openness with others. The research team led by Jennifer M. Mitchell from the University of California combined MDMA with psychotherapy, a practice known as MDMA-assisted therapy (MDMA-AT).
The study involved 104 adults recruited from the United States and Israel with moderate to severe PTSD who had not responded to previous treatments. They were randomly assigned to receive either MDMA-assisted therapy (MDMA-AT) (53 participants) or placebo with therapy (51 participants). MDMA-AT consisted of three sessions of MDMA (80–120 mg) with psychotherapy, spaced about 1 month apart, plus 12 sessions of 90-minute therapy (without drug consumption). The placebo with therapy group received identical therapy sessions but instead consumed placebo pills.
The researchers measured the participants’ PTSD symptoms and functional impairment levels before and after the treatment, using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scale, and Sheehan Disability Scale (SDS), respectively. They found that MDMA-AT significantly reduced PTSD symptoms and functional impairment compared to placebo with therapy.
Mitchell and colleagues also discovered that more participants in the MDMA-AT group achieved clinically meaningful improvement – 86.5% in the MDMA-AT group compared to 69% in the placebo with therapy group. Additionally, 71.2% of participants in the MDMA-AT group were no longer clinically diagnosed with PTSD, compared with 47.6% in the PTSD group. The treatment effect of MDMA was also not influenced by disease severity, trauma type or comorbidities.
The researchers also found that MDMA was generally well tolerated, with no serious or life-threatening events that led to hospitalizations, disability, or deaths. The most common side effects of MDMA were muscle tightness, nausea, decreased appetite and sweating, which were mostly mild or moderate and transient. MDMA caused temporary increases in blood pressure and heart rate, which were expected side effects.
Suicidal ideation was observed in both groups, as is consistent with PTSD symptoms. However, MDMA did not increase the risk of suicidal ideation or behavior, or MDMA abuse or dependence.
Notably, the study included a diverse population of participants with moderate to severe PTSD and various trauma histories and comorbidities. “In a historic first, to our knowledge, for psychedelic treatment studies, participants who identified as ethnically or racially diverse encompassed approximately half of the study sample,” the researchers highlighted, as 26.9% of participants identified as Hispanic/Latino, and 33.7% identified as other than White.
Study author Mitchell emphasized the importance of this inclusivity, “due to disparities in trauma exposure, gender-diverse and transgender individuals, ethnoracial minorities, first responders, military personnel, veterans and victims of chronic sexual abuse have a disproportionately higher risk of developing PTSD. However, these diverse populations are historically underrepresented in clinical trials.”
Some limitations are to be noted. For example, there is a lack of a comparison with other treatments for PTSD, such as selective serotonin reuptake inhibitors (SSRIs). The study also excluded participants with high suicide risk, comorbid personality disorders and underlying cardiovascular disease, which may limit the generalizability of the findings.
Nevertheless, the study was a large, rigorous and confirmatory phase 3 trial that followed FDA guidance, and MDMA-AT could be a promising new treatment for individuals with PTSD who do not respond to current therapies.
The study, “MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial”, was authored by Jennifer M. Mitchell, Marcela Ot’alora G., Bessel van der Kolk, Scott Shannon, Michael Bogenschutz, Yevgeniy Gelfand, Casey Paleos, Christopher R. Nicholas, Sylvestre Quevedo, Brooke Balliett, Scott Hamilton, Michael Mithoefer, Sarah Kleiman, Kelly Parker-Guilbert, Keren Tzarfaty, Charlotte Harrison, Alberdina de Boer, Rick Doblin, Berra Yazar-Klosinski and MAPP2 Study Collaborator Group.