In the 1970s, MDMA was used as an adjunct to psychotherapy and was thought to help people confront their feelings and open up to their therapists. Its therapeutic potential, however, began to be overshadowed by its recreational use in the 1980s. MDMA became popular at clubs and raves and its reputation as a party drug, commonly called Ecstasy or Molly, led to its criminalization in the United States in 1985. 

In recent years, researchers have been re-evaluating MDMA as a potential therapy, this time for conditions such as posttraumatic stress disorder (PTSD) and drug dependence. 

Structural model of MDMA.

Three Brown faculty members—Carolina Haass-Koffler, associate professor of behavioral and social sciences and psychiatry and human behavior; Erica Eaton, assistant professor of psychiatry and human behavior and of behavioral and social sciences; and Christy Capone, assistant professor of psychiatry and human behavior—are at the forefront of this research and are launching the first-ever study of MDMA-assisted therapy for veterans with co-occurring PTSD and alcohol use disorder (AUD).

The team is hopeful that their study, supported by a Seed Award from Brown University’s Office of the Vice President for Research and funding from the Center for Addiction & Disease Risk Exacerbation (CADRE), will provide much-needed evidence of the safety, feasibility, and acceptability of the MDMA treatment option for veterans who have not been able to find relief from other forms of medication or therapy.

“It’s exciting to be on the front edge of this,” said Professor Eaton, “because so much of the potential is really unknown.”

The After-War

PTSD occurs after experiencing or witnessing a life-threatening or traumatic event. Pulitzer Prize-winning journalist and MacArthur Fellow, David Finkel, defines it as “a mental-health condition triggered by some type of terror, or a traumatic brain injury, which occurs when the brain is jolted so violently that it collides with the inside of the skull, causing psychological damage.”

“Every war has its after-war,” Finkel writes: “depression, anxiety, nightmares, memory problems, personality changes, suicidal thoughts.” According to the US Department of Veterans Affairs, 11% to 20% of Iraq and Afghanistan veterans experience PTSD in a given year. By extension, the most recently assessed veteran suicide rate was a staggering 57.3% higher than that of non-veteran adults.

Professors Eaton and Capone have worked on the PTSD crisis during their many years as clinicians at the Providence VA Medical Center. They are all too familiar with the attempts of patients to manage symptoms with alcohol, and PTSD’s notorious resistance to standard treatments.

Professors Eaton and Capone have worked on this crisis during their many years as clinicians at the Providence VA Medical Center. They are all too familiar with the prevalence of PTSD among veterans, the attempts of patients to manage symptoms with alcohol, and PTSD’s notorious resistance to standard treatments.

Available PTSD-AUD therapies effectively help “only a fraction of people who engage in them,” they write. The persistence of the problem, despite the array of approaches and clinical hours devoted to it, has led to a “growing interest in alternative medications, including psychedelics.”

The results so far have been amazing. This is far and away much greater efficacy than meds and psychotherapy. And then there’s the longevity of those effects. We just do not see that sort of effectiveness elsewhere or with other treatments.

Erica Eaton, assistant professor of psychiatry and human behavior and of behavioral and social sciences

Early studies into MDMA-assisted therapy for PTSD have been so impressive as to be startling: “Placebo-controlled study of participants with treatment-resistant PTSD showed that 85% of those in the MDMA study (compared with 15% in the placebo group) no longer had a diagnosis of PTSD after three sessions of MDMA-assisted psychotherapy,” write Ben Sessa and David Nutt for the British Journal of Psychiatry. “And the results were sustained at 3.5 years long-term follow-up.”

“The results so far have been amazing,” says Eaton. “This is far and away much greater efficacy than meds and psychotherapy. And then there’s the longevity of those effects. We just do not see that sort of effectiveness elsewhere or with other treatments.”

Capone adds: “And this occurs with only one course of treatment. The patients are not on daily meds. And they continue to get better. It’s quite different from anything we’ve seen before. We’re looking at brain changes. The process continues after they’ve finished with the treatment.”

With conventional therapies, says Capone, “patients leave the VA and, very often, come right back. The treatment doesn’t stick and there’s a high dropout rate. Many patients were coming through the program and not benefitting. MDMA is like night and day.”

Heeding the Science

How does MDMA-assisted therapy produce these results? There are a few hypotheses. One is that MDMA reduces inflammation in the brain caused by PTSD. Researchers also posit that it “improves bonding and raises levels of empathy, empathetic understanding, and compassionate regard.” Professors Eaton, Capone, and Haass-Koffler write that the “combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection.”

“Essentially what it can do is increase the brain’s ability to hold more serotonin,” Eaton said, “and it seems as though that can be the driving force. It also increases oxytocin, which is known as the caregiving or love hormone. And we think that is a really important aspect of the assisted therapy part of the program and why it can be so impactful; because the trust between the participant and the therapist allows for the space for these changes to occur.”

There is a caveat: “There has been much news around psychedelics over the last several years,” says Eaton. “There is some well-earned enthusiasm, but we should remain cautious. Private companies want to capitalize on this. It’s a little worrisome. Some will try to use this as a moneymaker without trying to do it justice. We’re hoping that the profit-motive doesn’t outpace the science.”

First Steps

Brown’s pilot study will officially begin in February 2023. It is the first step in creating a body of work and infrastructure around the issue. The larger plan is to form a center for psychedelics research at the Center for Alcohol and Addiction Studies (CAAS).

The clinical team conducting the study is composed of four certified therapists who are currently training with the Multidisciplinary Association for Psychedelic Studies (MAPS), which is one of the working bodies sponsoring trials to investigate the efficacy of MDMA-assisted therapy on veterans with PTSD. MAPS spearheads negotiations with the FDA and supports the study at Brown.

“It’s a big undertaking for therapists and participants alike to go through 15 therapy sessions,” says Eaton, “and then two eight-hour-long sessions of MDMA treatment. It’s also resource intensive as therapists work in pairs during those two full days when MDMA is administered.”

In addition to the Providence VA, MAPS, CADRE, and CAAS, the study involves the Warren Alpert Medical School. 

“We’re excited about forming this great collaboration with Dr. Haass-Koffler, who has her own expertise in pharmacokinetics and biomarkers,” says Eaton. We’re building a really good team and looking into what we can explore further.”

“I think we feel such an urgency to explore other treatment options,” says Capone, “not just because veterans don’t get much better under the conventional protocols, but because some of them are dying or have died under our watch. That really drives us forward to explore MDMA therapy.”

“It’s a real crisis among our veterans and the mental health system in general,” says Eaton. “To have a program that puts people in a better place—and to be able to lower the suicide rate—is frankly magic and a real beautiful thing to be a part of.”