Unlocking the Potential of MDMA

“People are dying,” Capone said. “There’s a pretty high suicide rate among Veterans. Some of the risk factors for suicide are PTSD and substance use. Veterans that have sought treatment and have not benefited are pretty demoralized.”

Capone has lost Veterans to suicide in her clinical work. “It’s pretty intense,” she said. “So I feel like we need to think outside the box and be open to exploring additional options. That’s what drives me forward; I feel like there’s a critical need.”

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

This study is also personal for Haass-Koffler who served in the Italian military and was deployed during the Somalian Civil War, the Rwandan Genocide and in the ethnic wars in former Yugoslavia during the 1990s. 

“I watched firsthand the trauma and the violence that happens in a war zone,” she said. “When I returned from my first tour in Somalia, it was hard, I have to say. But the most difficult part was coming back from the second tour because I realized that these negative experiences were accumulating and negatively impacting my day-to-day life. They were building up one tour after another.”

Haass-Koffler, whose research involves examining biobehavioral mechanisms of addiction, believes the pairing of pharmacology with clinical psychology is the key to finding a way forward for Veterans. “I don’t believe in a silver bullet,” she said. “But when we combine the two treatments, there is potential. Neither MDMA nor clinical therapy by themselves are sufficient for this very fragile population.” 

Why MDMA?

A recent study into MDMA-assisted therapy for PTSD has produced impressive results: 86.5% of participants with treatment-resistant PTSD achieved clinically meaningful improvement, 71.2% no longer met criteria for PTSD, and 46.2% met remission criteria by the study’s end. For the placebo group, the results were 69%, 47.6% and 21.4%, respectively.

“The results so far have been amazing,” Eaton said. “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.”

“Part of what MDMA does is increase feelings of connectedness, trust and empathy,” Capone said. “It can also reduce some of the fear of confronting traumatic memories. Less fear and more openness is a good state to be in to work through some really difficult things.”

MDMA “allows the patient to go through mental processes that externalize their intimate trauma experience,” Haass-Koffler said. “The medication itself allows access to memories that are deep in the brains of those individuals. This is where assisted therapy comes in because those experiences are going to be guided by the clinical psychologist in the room.” 

“Essentially what MDMA 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; the trust between the participant and the therapist allows for the space for these changes to occur.”

Capone points out that MDMA is not a classic hallucinogen like psilocybin mushrooms or LSD. Although it may induce some hallucinatory imagery, the power of MDMA lies in its ability to promote empathy and prosocial feelings. MDMA is “more about breaking down barriers and processing what’s there,” she said. 

As part of her training, Capone has spent countless hours studying videos of patients undergoing MDMA-assisted therapy. “I’ve seen people get so much further down the road after this experience; it seems to jumpstart their progress,” she said. “Some of the Veterans I’ve worked with have deployed three or four times and have had multiple horrendous experiences. They avoid talking about it because it’s so distressing. So if they can approach rather than avoid it, and if the imagery, setting and relationship with the therapist are helpful, it can be pretty compelling.”

The Brain on MDMA

Haass-Koffler, whose expertise extends to pharmacokinetics and biomarkers, and whose role in the study includes examining the effects of MDMA on the brain, is conducting MRIs on each participant before and after the course of treatment.

“We’re investigating changes in the brain, such as rewiring, altered connectivity, and reduced inflammation, to understand why symptoms improve following medication and therapy,” she said. “Our goal is to identify specific biomarkers in the brain to assess differences before and after therapy.”

This is crucial information for the FDA, which requires biomarkers to evaluate the effectiveness and safety of this approach. “We are rigorously following all necessary procedures and collecting substantial data,” Haass-Koffler said. “Our aim is to provide biomarkers that can give the FDA confidence in the observed brain changes, which we can measure accurately.”

What Success Looks Like

Capone, Eaton and Haass-Koffler will gauge the success of this study by examining MDMA’s impact on alleviating PTSD symptoms and reducing alcohol use. They will also evaluate its effects on depression, suicide, suicidal ideation and overall quality of life. 

The MRI component is especially important because researchers don’t fully understand how MDMA works, how it affects the brain or how long the positive effects last. One recent study showed a significant reduction of PTSD symptoms for at least one year after treatment.

“We’re excited to be part of that conversation and to show what we’ve found,” Capone said. “We have the opportunity to extend from the comorbidity of PTSD and AUD to opioid use disorder, because with Veterans, it’s not just alcohol; it can also be methamphetamine or cannabis.

“When people are in extreme distress, many substances come into play. So if successful, we can do a bigger or more expansive trial,” she said. “That’s our next frontier.”