The path toward federal approval for medical treatments involving psychedelics may be longer and less straightforward after the US Food and Drug Administration denied the first application for a treatment in this category, but experts say the work is far from over.
On Friday, the FDA declined to approve the use of MDMA, commonly known as ecstasy, as a treatment for post-traumatic stress disorder, according to a news release from drug sponsor Lykos Therapeutics. The company says the agency has requested an “additional Phase 3 trial to further study the safety and efficacy” of the treatment.
The initial application from Lykos presented positive data from two late-stage clinical trials that used MDMA in combination with talk therapy to treat PTSD. But in June, an independent FDA advisory committee voted overwhelmingly against the treatment, citing concerns about the integrity of the particular trials up for review – notably regarding missing information about safety and bias in efficacy data. The advisers said it was also difficult to parse how much the accompanying talk therapy — an area that the FDA does not regulate — contributed to outcomes.
Lykos said Friday that it plans to seek a meeting with the FDA to discuss its recommendations and ask the agency to reconsider, confident that the concerns raised by the FDA and its advisers can be addressed. Otherwise, conducting the additional trial could take years, Lykos said.
Advocates for the treatment, including some veterans groups, said they were “incredibly disappointed” by the FDA decision.
“While we remain confident MDMA-AT will eventually be approved, there is no doubt that this decision will lead to more unnecessary suffering and lives lost,” Martin Steele, president of the Veteran Mental Health Leadership Coalition, and Reason for Hope Executive Director Brett Waters said in a statement.
But experts say it’s important to honor the integrity of the scientific process. Dozens of clinical trials involving psychedelics are in various stages, and additional scrutiny can help strengthen the findings and build confidence.
“The whole field of science is one of peer review and critique. People are always weighing in, and hopefully that makes a better product. So hopefully all of this will lead to clarification,” said Dr. Rachel Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai’s Icahn School of Medicine. “There’s a difference between saying ‘We think this drug is dangerous’ and asking for more data.”
The FDA has a high bar for approval – and for good reason, said Dr. Michael Bogenschutz, director of the NYU Langone Center for Psychedelic Medicine.
“It’s frustrating to people who were hoping that this treatment would be found to be safe and effective and become available. I think we just need to take a deep breath and be patient and let the data accumulate to show more definitively, one way or the other, whether, in this particular case, MDMA can become a bona fide medical treatment for PTSD,” he said. “This was just one decision point along the road.”
Still, the FDA’s denial means that MDMA remains a Schedule I drug under the Controlled Substances Act, or a prohibited substance that has “no currently accepted medical use and a high potential for abuse.”
Drug trials that involve a controlled substance require a much more extensive approval process than standard treatments, involving significantly more logistics and expenses, Yehuda said. The additional barriers require people who undertake the work to be “highly motivated,” she said.
It can become risky when researchers are advocates instead of analysts, experts say.
“It’s really critical to research and to the sacred obligation of researchers to the general public to conduct studies with an open mind and with a degree of skepticism and to report the good and the bad results,” said Lori Bruce, who researches psychedelic ethics with the Oxford-NUS Centre for Neuroethics and Society and is associate director of the Interdisciplinary Center for Bioethics at Yale University.
“It’s OK for people to believe in a substance, but those conflicts of interest need to be reported.”
Studies retracted
On Saturday, one day after the FDA declined to approve an application for the use of MDMA as a treatment for PTSD, the journal Psychopharmacology retracted three studies about MDMA-assisted psychotherapy due to “unethical conduct” that was not disclosed before publication, the journal said. The studies were published in 2019 and 2020.
The “protocol violations” mentioned in the retraction notices occurred at a research site during a Phase 2 study on the use of MDMA-assisted psychotherapy, Psychopharmacology said.
The journal also said that the authors of the studies did not “fully declare a potential competing interest,” because at least two of the authors were affiliated with either the Multidisciplinary Association for Psychedelic Studies (MAPS) or one of its subsidiaries.
In early 2024, MAPS, a nonprofit research organization, spun off the company Lykos Therapeutics, which focused on getting FDA approval and insurance coverage for MDMA-assisted therapy for people with PTSD. MAPS announced in a January news release that it maintains select governance oversight of Lykos Therapeutics.
In 2019, MAPS posted a public announcement of ethical violations by investigators who had been involved in a MAPS-sponsored clinical trial of MDMA. A female participant in a study submitted complaints in 2018 about two therapists in Canada after one of the therapists “engaged in a sexual relationship with the participant,” MAPS said in an updated statement in 2022.
The two therapists verbally confirmed to MAPS that the “sexual relationship” occurred and were banned in 2018 from “all MAPS-related activities and from becoming providers of MAPS-affiliated MDMA-assisted therapy if the treatment is approved,” the statement said.
During the public comment section of an FDA advisory committee meeting in June, a statement was read on behalf of the female participant who made the complaints. In the statement, she said that she was “blindfolded, gagged, pinned, cuddled, and caressed” and that the assault was captured on video, which was later made public.
“I became suicidal during the trial, leading to a near missed attempt. Lykos was informed and chose not to document it. Undoubtedly, it was an adverse event and they hid it,” the participant’s statement said.
Earlier in the same meeting, a Lykos representative said, “it’s never OK for a care provider to cross boundaries. It’s unethical behavior,and it’s malpractice. We work with licensed and health care providers now only, and they are trained, in addition through our therapy training program, to understand how the drug may impact boundary-setting for patients and to reinforce an upholding of boundaries on their part of things, as well.”
According to the retraction notices, four of the study authors disagreed with the retractions, and one of the study authors said she agreed with the retractions “but disagrees with the wording of the retraction notice.” The other authors did not respond to the journal.
“The ethical violations at issue were reported to the FDA, Health Canada, and the Institutional Review Board (IRB)/Independent Ethics Committee (IEC), and a public statement was issued in May 2019. However, we did not disclose the violations to the journal itself, an additional step we should have taken and regret not doing. The journal also raised an issue regarding disclosure around conflict of interest, however, the authors did appropriately disclose contributions, funding sources, and affiliations,” Lykos said.
Psychopharmacology did not allow the study authors to publish a correction with data that excluded findings from one study site, said Allison Feduccia, an author in all three retracted studies.
Lykos also said the articles “remain scientifically sound and present important contributions to the study of potential treatments for PTSD.”
“It is important to note that these are not the efficacy data that was submitted to the FDA, and this was not the basis for their decision to issue a Complete Response Letter,” the company said in the statement.
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The retractions were “an additional disheartening surprise for psychedelic science” but an important emphasis on the importance of having high-quality data, said Dr. Brian Barnett, a psychiatrist who leads psychedelic research for Cleveland Clinic.
“Integrity matters in every arena of science, and psychedelic science is no exception,” he said. “Hopefully, these retractions will help ensure high quality and transparency in the rapidly growing field of psychedelic science in years to come.”
This integrity is key to building public trust and confidence in the way drugs are vetted, experts say.
“Right now, we are aware that some people do indeed have positive outcomes from psychedelics. We also know that some smaller percentage are going to have negative outcomes, sometimes for years, and we don’t yet know who is more likely to have the positive experience and who is more likely to have the negative experience or long term harms,” Bruce said.
“We need to find better solutions to address the mental health crises that are occurring in our country. Absolutely, it could be that psychedelics have a tremendous impact for patients, and I would love to see that happen, but we just need to proceed cautiously and examine all the data, not just the data that support a certain interest.”