Expert Panel Delivers Major Setback to MDMA Proponents
A panel of experts advising the Food and Drug Administration (FDA) on the use of the psychedelic MDMA for treating post-traumatic stress disorder (PTSD) concluded on Tuesday that the existing evidence does not demonstrate the drug’s effectiveness or prove that its benefits outweigh its risks. This decision poses a significant challenge to the drug’s proponents and its sponsor, Lykos Therapeutics, potentially jeopardizing FDA approval.
Panel’s decision
After a day of public comments and discussions, the panel voted 9-2 against the effectiveness of MDMA combined with talk therapy for treating PTSD. Additionally, they voted 10-1 that the benefits of MDMA treatment do not outweigh its risks. While the FDA often heeds the panel’s advice, it is not bound to follow their recommendations. However, given the numerous concerns raised, it is likely the FDA will align with the panel’s stance.
Research shortcomings and allegations of misconduct
FDA staff and advisory panel members highlighted significant shortcomings in the clinical research, including data uncertainties, unanswered questions about potential abuse, and a lack of evidence supporting the psychological approach used in therapy sessions.
“There are so many problems with the data,” said Melissa Barone, a psychologist with the VA Maryland Health Care System. “Each one alone might be okay, but when you pile them up on top of each other…”
Panelists also addressed allegations of possible misconduct and bias in the trials that could have skewed the results. “I have real concerns with the validity of the data and the allegations of misconduct,” said Elizabeth Joniak-Grant, a sociologist on the panel. The FDA acknowledged ongoing investigations into these claims but did not provide details.
Advocates for MDMA therapy
Despite the overall skepticism, some panel members supported the treatment. Dr. Walter Dunn, a psychiatrist at UCLA, voted in favor of the therapy’s efficacy, noting that the effect sizes were significant enough to indicate potential effectiveness for PTSD, even considering the allegations of misconduct.
Implications for psychedelics
The panel’s decision comes at a crucial moment for the broader effort to expand access to psychedelics. MDMA would be the first new PTSD treatment to hit the market in decades and a milestone for psychedelic therapies. “We are charting new territory,” said Kim Witczak, a consumer representative on the FDA’s advisory committee. “We want to set it up right.”
Proponents’ perspective
Representatives from Lykos emphasized the positive findings from clinical trials, noting that 67% of participants in the MDMA treatment group no longer met the diagnostic criteria for PTSD after three sessions, compared to 32% in the placebo group. “These results support that MDMA combined with psychological intervention provides significant reductions in PTSD symptoms,” said Berra Yazar-Klosinski, Lykos’s chief scientific officer.
However, the FDA staff and advisors raised concerns about “functional unblinding” in the studies, where participants could tell if they had received the experimental drug, potentially affecting the results. “Although we have two positive studies, the results are in the context of dramatic functional unblinding,” said Dr. David Millis, an FDA clinical reviewer.
Concerns about abuse potential
Another potential sticking point was the lack of data about how patients experienced the acute effects of the drug, including feelings like “euphoria” or “elevated mood.” That data helps inform the FDA’s assessments of the drug’s abuse potential.
“We noticed a striking lack of abuse-related adverse events,” said David Millis, an FDA clinical reviewer, noting that the FDA had advised the study sponsors to collect this type of data.
While MDMA is currently listed as a Schedule I drug, the agency’s review found it has the same abuse potential as a Schedule II stimulant, a category that includes cocaine.
“We’re actually managing more and more severe cases of MDMA overdose, and so I’m less concerned about the safety in the acute setting, but more chronically if they go on to abuse MDMA,” said Maryann Amirshahi, a professor of emergency medicine at Georgetown University and a committee member.
Study data and long-term effects
About 40% of those enrolled in the MDMA study had a history of using it prior to the study. Alongside its positive findings on the short-term effects of MDMA, Lykos presented data from a follow-up observational study intended to assess the durability of the treatment. While not yet published in a peer-reviewed journal, that data “suggest evidence of MDMA’s durability to at least six months,” said Berra Yazar-Klosinski, chief scientific officer for Lykos.
However, FDA staff highlighted issues with the long-term data, including a 25% dropout rate and the fact that some participants sought additional therapy and, in some cases, used illicit drugs, including MDMA.
Future of MDMA for PTSD treatment
The form of talk therapy used in the MDMA sessions also troubled some on the panel who noted there wasn’t strong data to support its use outside of the trial. “The psychological intervention is still for me a bit of a black box,” said Dr. Paul Holtzheimer with the National Center for PTSD. “What was described is really a relatively vague, ill-defined treatment.”
Despite some positive clinical trial results from Lykos Therapeutics, the panel’s decision underscores the complexity and challenges in approving new treatments, especially involving psychedelics. The significance of this moment in the broader effort to expand access to psychedelics was acknowledged, but the path forward remains uncertain given the concerns raised.