A federal advisory committee meets today to weigh the risks and benefits of using MDMA, commonly known as ecstasy, as a treatment for post-traumatic stress disorder.
MDMA is classified as a schedule I drug under the Controlled Substances Act, and approving it would be a marked shift. It’s the first time the FDA’s advisers have considered a psychedelic drug for medical use. The novel treatment has the potential to transform a field with significant need, but critical questions loom.
About 5% of adults in the United States – about 13 million people – experience PTSD in any given year, according estimates from the National Center for PTSD. But current treatment options – including antidepressants and some specialized forms of cognitive behavioral therapy – are limited in their scope and effectiveness, with few alternatives available to help those don’t respond well to them.
Lykos Therapeutics has promising data from two late-stage clinical trials that used MDMA in combination with therapy to treat PTSD. MDMA is a psychedelic drug known as an entactogen, a class of psychoactive drugs that produce experiences of emotional communion, relatedness and emotional openness.
About 200 people participated in the Lykos trials, with a treatment program that involved three eight-hour sessions where participants took MDMA in the presence of two therapists. The MDMA sessions were spaced about a month apart, along with additional therapy sessions.
“Participants appear to experience rapid, clinically meaningful, durable improvement in their PTSD symptoms,” the US Food and Drug Administration wrote in a briefing document about the studies.
But the agency also noted that “several factors make these data challenging to interpret and complicate the benefit-risk assessment for this application,” posing key questions for the members of the Psychopharmacologic Drugs Advisory Committee to consider.
As they weigh the risks and benefits of the novel treatment at today’s meeting, the committee members will hear presentations from Lykos and the FDA, along with comments from the public.
The FDA has final say on approving the treatment and will often follow the committee’s recommendations but does not have to do so.
The studies were designed to be double-blind, meaning neither the participants nor the researchers knew who received the MDMA treatment and who didn’t. This type of study is considered the gold standard because it helps reduce bias in results by minimizing the effects of external factors. But MDMA’s hallucinogenic effects have “profound alterations” on a person’s state of being, and the vast majority of participants knew which group they were in simply by the nature of their experience.
The Institute for Clinical and Economic Review, a nonprofit that conducts independent reviews of treatments, tests and procedures, also cited “substantial concerns about the validity of the results” of the Lykos trials in a report published in March. Those concerns centered around bias, both from the unblinding of the trial and from other influences on patient perspectives.
In addition to blurry data on efficacy, there were concerns about safety data, the FDA said.
It is known to have potential for abuse, but the FDA cautions that the research did not appropriately assess this as an adverse event in the context of the treatment program.
Reports from illicit use of MDMA suggest that it may pose risks to both heart and liver health. The phase III clinical trials showed “significant increases in both blood pressure and pulse” among participants, the FDA said, but certain related assessments were incomplete. And liver health was assessed only in small groups from earlier phases of the clinical trials.
The questions are all familiar to Lykos, and the company has had conversations with the FDA throughout its research, CEO Amy Emerson said. The advisory committee meeting is the “next big milestone” in the process and an opportunity to gather even more information, she said.
“There’s just such an urgent patient need for new treatment options, and we really use that as our guiding light as we develop MDMA-assisted therapy,” she said. “All along, we’ve been really committed to safety, and that will always be top of mind.”
There is growing interest and support to explore the use of psychedelics as therapeutics. Along with MDMA, drugs like ketamine and psilocybin mushrooms are being studied in clinical trials to treat a variety of mental health disorders.
“Depression, PTSD, eating disorders – they’re all different. You can’t just lump these together and say, ‘Psychedelics are good for this,’” Emerson said. “You need to study it, you need to look at the safety and efficacy profiles of each, and we have to be careful to not treat these things as panaceas or like a magic bullet.”
The Lykos treatment is the first to reach this point in the process, and the way the FDA and its advisory board proceed could set key precedents.
“It’s an early but exciting moment. The promise is there, the potential is there, and we just have to find out through careful study and time how impactful these medications will be,” said Dr. Joshua Gordon, director of the National Institute of Mental Health.
Many questions remain about the specific conditions needed to achieve effective use of this treatment, and the FDA advisers could choose to endorse it under a wide range of stipulations or not at all, he said.
Still, even the most supportive experts caution about the limitations of the treatment.
“I hope that the drug gets approved but in a way where it can be made available and monitored in a responsible manner,” said Dr. Rachel Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai’s Icahn School of Medicine, who is not a member of the FDA advisory committee. “My fear would be that we stop being curious, we stop asking the right questions, we stop trying to figure out mechanisms of action, we stop trying to perfect and scale like we do with any other treatment.”
It’s critical to protect vulnerable populations who may benefit from this treatment, experts say.
“There’s a recognition that psychedelics are probably uniquely susceptible to the blurring of the boundaries between strictly applied medical treatments that are provided by experienced clinicians under very well-monitored circumstances versus recreational use, so there’s a great interest in trying to get this as right as possible,” said Dr. Jon Alpert, chair of the American Psychiatric Association’s research council and chair of the department of psychiatry and behavioral sciences at the Albert Einstein College of Medicine.
“The last thing you want is for a promising treatment for a devastating condition to go off the rails in an unbounded, unmonitored kind of use.”
Also, the trials so far have excluded people who may be most vulnerable to substantial side effects of MDMA, such as adolescents and those with coinciding conditions such as schizophrenia or bipolar disorder, and it’s important to continue gathering data to understand how the treatment works in these populations, he said.
“Any FDA approval of MDMA must be accompanied by rigorous regulations, strict prescribing and dispensing controls, comprehensive patient education, and ongoing monitoring and surveillance systems,” the American Psychiatric Association wrote in a letter to FDA’s advisory committee.
In addition to potentially setting a precedent in mental health treatment, the particular treatment program that Lykos has studied is “labor-intensive,” she said. It requires a significant amount of investment – both logistically and emotionally – from participants and providers, which is challenged by the shortage of mental health professionals in the US.
“We never had a situation where something that the government had deemed harmful gets a 180 and becomes an approved treatment for a condition,” Yehuda said. “Then, the question is, ‘Are we going to be able to use the moment in a way that really furthers the mental health of our population?’”