Today, a Federal Drug Administration advisory committee held a public hearing to evaluate the evidence on MDMA treatment for post-traumatic stress disorder, voting in a non-binding manner against approval of the treatment – which indicates a good chance that the FDA will follow suit in its official determination. , and setting a handful of precedents for efforts to legalize other psychedelics that follow closely behind.
The FDA’s decision is expected by August 11, and if MDMA treatment is approved, it will mark the true beginning of the end of the psychedelic ban that has stifled research since 1970. It would also be the first new treatment for PTSD for over two years. decades, a condition that affects approximately 13 million Americans. But some prominent researchers have decried a “psychedelic hype bubble” that inflates expectations over what peer-reviewed evidence actually supports. As legalization looms, the unfolding drama tests the strength of the evidence.
Lykos Therapeutics, the company that submitted the application in February, is now facing criticism over the integrity of its clinical trial data. Concerns range from methodological issues around the development of placebos for psychedelic experiences that could bias results to questions of ethical misconduct, where internal pressures to report positive experiences may have affected participants’ responses.
Formerly known as MAPS Public Benefit Corporation, Lykos Therapeutics – spun off from MAPS, the organization that has worked to approve MDMA since its founding in 1986 – has conducted two Phase 3 clinical trials, each with impressive results . The first trial found that MDMA therapy successfully treated 67 percent of participants, reducing their symptoms to the point that they no longer met criteria for PTSD. In the placebo group, this figure was 32 percent. The second trial found similar results: 71 percent of the treatment group no longer met criteria for PTSD, compared to 48 percent of the placebo group.
In March, the Institute for Clinical and Economic Review, or ICER, a nonprofit that evaluates new medical treatments, released a report highlighting placebo bias and ethical concerns in the Lykos data. A group of Lykos therapists and trial participants pushed back against the criticism, launching a saga that is still ongoing.
Then, in April, a citizen petition was submitted to the FDA and has now gathered 88 signatories from across the field, calling for a public hearing to highlight these overlooked concerns and bring them to the FDA’s consideration. They do not focus on the risks of psychedelics in general, but on the application of Lykos in particular and their protocol that explains how to manage mixing suggestibility-enhancing drugs with psychotherapy.
Today’s hearing of the Advisory Committee on Psychopharmacologic Drugs lasted an entire day, providing a forum for public comment, reviewing the evidence of safety and effectiveness, and ultimately voting that the evidence does not support still approval.
As for whether the available data suggests MDMA therapy is effective for treating PTSD, nine voted no, two voted yes. As for whether the benefits of treatment, as well as the FDA’s proposed risk assessment and mitigation strategy, outweigh the risks of treating PTSD patients, only one in 11 people voted yes . “I don’t think we’re there yet,” said Kim Witczak, a consumer representative on the advisory committee.
It’s now up to the FDA to decide whether it agrees.
What’s wrong with MDMA therapy?
Amid a deluge of headlines and editorials in prestigious journals that herald psychedelics as the start of a new paradigm in mental health treatment, ICER recently voted 14-1 that the evidence Current studies do not demonstrate that MDMA-AT (MDMA-assisted therapy) is a net benefit, let alone better than other treatments. It caused a sensation.
Some of ICER’s concerns have been well known to researchers for years, such as “functional unblinding.” Simply put, it’s very difficult to prevent someone from knowing whether you’ve given them a psychedelic, which undermines blinding, one of the key pillars of placebo-controlled research. It should be noted, however, that unblinding is not a problem unique to psychedelics. Failures in successful blinding have already been recognized in other approved drugs, from opioids and antidepressants to a version of ketamine.
And for unblinding to become a hurdle now would be a bit strange, since the FDA began working with MAPS on the design of their Phase 3 trials in 2017, including approving the methodology for this kind of delicate questions.
Other concerns on the agenda include safety, such as cardiovascular risks due to elevated heart rate and blood pressure, the contribution of psychotherapy to the overall effectiveness of treatment, and the myriad of small details related to the provision of complex treatment such as MDMA therapy.
But at the center of the recent debate are ethical concerns surrounding the conduct and direction of Lykos’ MDMA trials. Beyond placebo concerns, ICER raised concerns that some participants felt “compelled to report good results and suppress bad results” so as not to hinder the overall success of approval of the drug. MDMA.
Testimony submitted to the FDA by a participant in a Phase 3 MAPS trial reportedly claimed that at least three people who received MDMA during the trial reported worsening suicidal tendencies in the weeks that followed – a detail which did not appear in published journal articles. about the trial (Lykos responded that all adverse events were reported to the FDA).
Additionally, the same participant alleges that their trial therapists repeatedly told them that they were “helping to make history” and reminded them that their “responses and behaviors during and after the trial could jeopardize the legalization.”
To learn more about the potential effects of legal access to drugs like MDMA on millions of Americans, it is important that study participants feel free to share everything about their experiences, not just the good ones. things. Smothering participants with the political implications of their experiences speaks to a broader climate of “psychedelic evangelism,” which threatens to undermine the validity of the science that advances the movement.
As Olivia Goldhill reported in STAT, the FDA did not include concerns about data suppression in its pre-meeting materials, indicating that it did not find a problem with the reporting of negative events from the test. But during an oral presentation at the hearing by Neşe Devenot, a lecturer at Johns Hopkins University and co-author of the citizen petition submitted to the FDA, she highlighted problems with Lykos’s particular treatment protocol, citing incidents of sexual misconduct and therapists restricting participants during MDMA sessions. Devenot added: “Lykos says its training will ensure boundaries are maintained. But his intervention increases the risks for participants by encouraging “border violations,” where we are sure to see these issues raised.
Although Lykos’ application is the first drug in the broad psychedelic field to be considered for approval by the FDA, others are not far behind. A psilocybin analogue received breakthrough designation from the FDA in 2018 as a treatment for depression, and an LSD formula received the same designation for anxiety earlier this year.
The broader momentum toward legalizing psychedelic therapies will survive this particular approval anyway, but the stakes are high. The FDA’s verdict on the Lykos application will set precedents for other psychedelic drug applications that will surely follow. And if the application is not approved, it would delay the time frame in which PTSD patients could access treatment (which, for critics of the Lykos model, is a good thing, as they fear we will not we don’t know enough about the treatment). Lykos treatment protocol to quantify the risks).
There is also the question of drug classification. If MDMA were approved, it would likely be reclassified by the DEA from a Schedule I substance, defined as one with no accepted medical use, to something more lenient. This would have ripple effects across the entire psychedelic ecosystem.
An Annex I status makes it difficult to obtain funding for research, limits enrollment in clinical trials, and limits the production of the drugs themselves. Reclassifying MDMA would ease all of these restrictions, ultimately supporting a stronger research base. Meanwhile, states that get ahead of the federal government in legalizing various forms of access to psychedelics — like Oregon’s adult-use model — would face less red tape.
Overall, the FDA must decide whether the benefits of Lykos’ MDMA-AT proposal outweigh the risks. Today’s vote suggests they will likely say no, pushing back the end of the ban. But especially when it comes to psychedelics, anything can happen.
Update, June 4, 6:10 p.m.: This story has been updated to reflect the FDA advisory committee’s vote.