FDA panel recommends against approval of ecstasy to treat PTSD

A U.S. Food and Drug Administration advisory committee overwhelmingly voted Tuesday that evidence is lacking that MDMA-assisted therapy is effective for treating post-traumatic stress disorder, and that the benefits don’t outweigh the risks to patients, dealing a potential blow to what could be the first psychedelic treatment the agency approves.

The advisory committee is made up of independent mental health and medical experts, and its vote is not binding. Still, its recommendation could hold great weight as the FDA decides for the first time whether the mind-altering compound - better known by its street name, ecstasy, and long categorized among the riskiest of controlled substances - can be legally used as a medical treatment in the United States.

During the all-day meeting, committee members praised the promise of the drug but struggled with gaps in the research data, potential for abuse of MDMA and how the psychotherapy, which is not regulated by the FDA, would be incorporated into the drug’s approval.

“The therapy itself is still, I would consider, experimental,” said Paul Holtzheimer, deputy director for research at the National Center for PTSD, who voted against approval.

The sponsor of the MDMA treatment, Lykos Therapeutics, conducted two late-stage clinical trials showing that patients treated with the drug experienced a significant improvement in their PTSD symptoms relative to those who got a placebo. The data, however, is uncommonly messy. Participants in the clinical trials also received various forms of psychotherapy, whose role wasn’t specifically measured in the results. The consciousness-distorting properties of MDMA also complicate the gold standard for clinical trials, which requires that participants not know whether they received a drug or a placebo.

“While we are disappointed in the vote, we are committed to continuing to collaborate with the FDA with their ongoing review,” Amy Emerson, Lykos’s CEO, said in a statement. She added: “There is an urgent need for new, effective and accessible therapies to address this unmet need for those living with PTSD.”

An approval would mark a watershed moment for advocates who believe psychedelic drugs best known for mind-bending trips or partying can successfully treat an array of mental health disorders. MDMA’s potential has been championed by veterans and others who suffer from PTSD, a condition afflicting an estimated 13 million in the United States but for which there are few drugs approved for treatment.

Should the drug fail to win approval, it would be a monumental setback for the field of psychedelic medicine and investors who have poured hundreds of millions of dollars into companies developing psychedelics to treat mental health conditions.

Ahead of Tuesday’s advisory meeting, the FDA’s own staff raised extensive questions about the potential skewing of pivotal late-stage trials because patients figured out whether they had actually received the drug. The agency also highlighted cardiovascular and substance abuse risks. On Tuesday, the committee voted 9-2 that the data doesn’t show the drug is effective in treating PTSD, and 10-1 that the benefits don’t outweigh the risks - even with the FDA’s proposed plan to mitigate them.

Jason Pyle, an independent doctor who serves as an unpaid member of Lykos’s board, cautioned against missing the larger picture. “In any pharmaceutical there are risks and questions, which is why we need the regulatory framework,” he said. “In the face of a veteran suicide epidemic and a community mental health crisis, we have to confront this with compassion, clarity and bravery.”

An FDA official, Tiffany R. Farchione, told the panel Tuesday that while the agency had asked Lykos to report impacts associated with abuse, the company did not note effects such as “euphoria” or “elated mood.” That will make it challenging for the FDA, if it approves the drug, to describe MDMA’s effects for labeling or for treatment recommendations, said Farchione, director of the agency’s psychiatry division.

Farchione said the lack of data collection “may have the greatest impact” on the agency’s decision.

Lykos’s senior medical director, Alia Lilienstein, acknowledged Tuesday that the company didn’t record euphoria and related effects but said it’s prepared to study that data if MDMA-assisted therapy is approved. She also allowed that Lykos’s application was complicated, adding, “Patients deserve us to work hard to figure out how to move something complicated forward.”

The federal government categorizes MDMA as a Schedule I controlled substance with no accepted medical use and a high risk of abuse, in the same class as heroin and LSD.

Lilienstein stressed that while MDMA has a “moderately high” abuse potential, it remains lower than drugs such as methamphetamine and produces no withdrawal symptoms.

Farchione also raised concerns about the effectiveness of the psychotherapy itself - which the FDA does not regulate. She added that while the agency could not label MDMA for use on its own, “we also don’t have strong evidence therapy is necessary.”

Committee members pressed Lykos officials on the company’s manual for therapy and how therapists were evaluated. They also raised concerns about the case of a female trial patient who said that in 2015 she was sexually abused by a male therapist, whose wife was also a therapist, during sessions that crossed ethical boundaries.

“Let’s try to not gloss over this misconduct - it was sexual misconduct,” said Elizabeth Joniak-Grant, a University of North Carolina at Chapel Hill sociologist and panel member who serves as a patient representative.

That patient, Meaghan Buisson, testified via a surrogate on Tuesday, pointing to a publicly available video of her session, which shows the therapists pinning her down, cuddling and stroking her. In an earlier interview with The Post, Buisson criticized the Multidisciplinary Association for Psychedelic Studies, or MAPS - the nonprofit parent of Lykos - for failing to keep her safe, glossing over harms and calling the therapy employed in the trials as “completely bunk.”

“How much information does the world need to recognize that MAPS cannot be trusted with these substances?” Buisson said.

A nonprofit affiliated with the American Psychological Association said in a letter to the FDA on Monday that it determined there is “insufficient evidence” for the advisory panel to recommend MDMA-assisted therapy for PTSD, citing concerns that the results may have been biased by participants who knew whether they received the actual drug or a placebo. That echoed concerns from the influential nonprofit Institute for Clinical and Economic Review, which published a draft report this year voicing “substantial concerns” about the research supporting the drug’s approval.

Committee members repeatedly grappled with allegations of clinical trial misconduct raised by public speakers and the ICER report, including claims that therapists discouraged patients from reporting adverse effects. The FDA’s Farchione said the agency could not speak about “what we are looking into” but added officials are aware of the report and “certainly take those allegations seriously.”

Lykos officials said that rollout of the drug would be limited and that the FDA’s proposed restrictions would include that the drug could be dispensed only in certain health-care settings - with a doctor available while the drug is administered, and at least two health-care providers to monitor a patient’s physical and psychological state for at least eight hours.