MDMA Shows Promise as Treatment for PTSD in New Clinical Trial

The drug could receive FDA approval by 2023, researchers said.

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The psychedelic drug MDMA, sometimes called "ecstasy" or "molly," may help people suffering from post-traumatic stress disorder (PTSD) when paired with talk therapy, according to new results from a phase 3 clinical trial.

The preliminary data was presented at the American Chemical Society's (ACS) Spring 2022 meeting in late March. The study helps pave the way for more research on MDMA, formally known as 3,4-methylenedioxymethamphetamine. Plus, the researchers say U.S. Food and Drug Administration (FDA) approval for MDMA-assisted therapy for PTSD may be on the horizon as early as 2023. Such a change could help millions.

"It definitely appears to be equally effective in people who are usually considered treatment resistant, so we're very excited to think that MDMA-assisted therapy is going to be an effective therapeutic in that hard-to-reach population," Jennifer Mitchell, PhD, the clinical trial's principal investigator and a professor of neurology at the University of California, San Francisco, said in a press release. Below, what to know about the new data—and how it could impact trauma survivors.

The New Clinical Trial Results

For the trial—the first of its kind for MDMA-assisted therapy for the treatment of PTSD—Mitchell and colleagues enrolled 90 participants with a severe form of the disorder.

Participants received the "optimal oral dosage of MDMA"—a full dose, followed by a half dose an hour later—which had been previously determined in phase 2 trials, or a placebo. After the half dose, participants attended an eight-hour psychotherapy session. They repeated the process twice, each a month a part. And they attended weekly therapy sessions in between.

Two months after their final session, two-thirds of the participants who received MDMA and therapy no longer met the criteria for a PTSD diagnosis, while only one-third of the participants who received a placebo with therapy no longer met the criteria. The researchers said participants did not exhibit any signs of addiction, and MDMA side effects, such as nausea and jaw clenching, were minimal.

Why MDMA for PTSD?

Selective serotonin reuptake inhibitors (SSRIs) are considered the first-line therapeutics for PTSD, but they're only effective for about half of patients, according to researchers. "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 in the press release.

Additionally, the American Psychological Association (APA) recommends cognitive behavioral therapy (talk therapy) for PTSD survivors. However, talk therapy on its own can be unhelpful, Geoff Bathje, PhD, a professor at Adler University and a psychologist at Sana Healing Collective, told Health.

"Talk therapy can be really triggering and activating when talking about your traumas," Bathje said. "MDMA really helps people stay regulated, stay present in their body, and stay connected to their therapist. So you can really see MDMA as a therapy facilitator."

It works this way because, according to Mitchell, MDMA is an empathogen. "It causes the release of oxytocin in the brain, which creates feelings of trust and closeness that can really help in a therapeutic setting," she said in the press release.

Bathje, who was not involved in the clinical trial, said the number of people living with PTSD may be "grossly understated," citing the fact that patients are often misdiagnosed with depression, or a panic disorder, or a different mental health issue, when PTSD would be a more accurate diagnosis. He added that trauma of any kind—such as war, sexual assault, abuse, illness, or a car accident—can lead to PTSD, but explained that not everyone who experiences a trauma will have it.

The condition manifests in different ways, and it can cause depression, anxiety, and even physical illness. For this reason, PTSD cases—and how they're treated—often look different from patient to patient.

"The landscape of what PTSD looks like and how it impacts people is so diverse," Bathje explained. "I think the treatments generally have needed to be pretty diverse too. As a result, you have people treated with dozens of different medications and dozens of different therapies."

Though the clinical trial showed the efficacy of MDMA for PTSD, both Bathje and trial researchers stated the importance of using MDMA in a therapeutic setting, instead of self-medicating. "If MDMA is decriminalized, that doesn't mean it's safe," Mitchell said. "It can be a very powerful tool, but it needs to have the right dose in the right context with the right support system."

"It really is the combination of talk therapy and MDMA, rather than just the molecule, that has the therapeutic effect," Bathje added. "The way I think about it is that MDMA helps shift somebody into a state where they can really take advantage of therapy."

The Future of MDMA-Assisted Therapy

Mitchell and colleagues are now recruiting participants for another phase 3 clinical trial to confirm the results. In the meantime, they're analyzing long-term data from their first phase 3 study to determine how long PTSD relief might last. The researchers report that their phase 2 participants have seen years-long benefits.

"They seemed to have a new perspective on life and engaged more," Mitchell said in the press release. "As their social skill set built up, they were happier over time." But she noted that the phase 3 trial participants had more severe PTSD symptoms than those in the phase 2 study, so their results may differ.

The following phase 3 trial is the next hurdle to overcome on the path to potential FDA approval of MDMA as a medication—and in making it accessible to clinicians and their patients. Ultimately, the drug needs to be rescheduled for providers and patients to benefit from MDMA as a medication. "It's currently a schedule I drug, with the government considering it to have no legitimate medical use," Bathje said. The classification also means the drug has a high potential for abuse.

The FDA's advisory board will need to review clinical trial data to assess MDMA treatment benefits and risks and to gain an overall picture. But board approval isn't the last step to making MDMA accessible. "Probably a last step for a lot of people will be getting the insurance companies to cover it to make it more affordable," Bathje said. "Pretty much any treatment is inaccessible to most people if it's entirely out of pocket."

In addition to insurance coverage, clinicians will have to be trained in using MDMA as part of therapy in order for the medication to be accessible. The Multidisciplinary Association for Psychedelic Studies (MAPS), which provided support and funding for Mitchell's recent research, has a training program.

But current research and training lacks a crucial component, according to some experts. "One major hurdle [for] the psychedelic research space is significant lack of diversity in both research subjects and research therapists," Gillian Scott-Ward, PhD, a clinical psychologist familiar with the MAPS MDMA-assisted therapy training, told Health.

Another consideration is the stigma associated with MDMA, a drug that has been illegal in the U.S., with a few exceptions, since 1985. "We've had a 50-year-plus war [on] drugs that has focused only on the harms and has either covered up, or minimized, or just refused to look at any of the potential benefits," Bathje said.

But, he added, FDA approval would legitimize MDMA as a therapy and start to remove its associated stigma. As more people experience benefit from the medication, that will also help, Bathje said.

Previous Research on MDMA and Other Psychedelics

The promising preliminary data from Mitchell and colleagues' phase 3 trial adds to a growing body of research supporting the therapeutic benefits of MDMA and other psychedelics when used in a medical setting.

Bathje and other researchers conducted a meta-analysis of placebo-controlled trials of psychedelic-assisted therapy since 1994, published in the Journal of Psychoactive Drugs in 2020. His team looked not only at MDMA, but also psilocybin (commonly called "magic mushrooms"), lysergic acid diethylamide (LSD), and ayahuasca (a hallucinogenic drink made from tropical botanicals).

Their analysis supported the effectiveness of psychedelic-assisted therapy across several mental health conditions, including PTSD, major depression, anxiety and depression associated with life-threatening illness, and social anxiety for those with autism spectrum disorder.

"When we looked at them all in combination," Bathje said, "what we found was that, really interestingly, it didn't matter what drug you were using or which condition you were treating. They all had about the same efficacy."

He added that many people go to therapy because they're "stuck" in a pattern of behavior, emotion, thought process, or even a relationship that isn't working for them. "I think psychedelics are really good at temporarily disrupting those things that we're stuck in," he explained, "and allowing us to consider some new possibilities, and to try out some new possibilities of thinking and feeling and behaving."

The new phase 3 clinical trial provides further evidence of the potential benefit of MDMA, Bathje said: "The current study is very consistent with our prior meta-analysis and very consistent with the previous MDMA clinical trials too."

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