The budding field of psychedelic drugs suffered a major setback on Friday. The FDA Refusal to approve MDMA-assisted therapy It called on the drug’s manufacturer, Lycos Therapeutics, to conduct another clinical trial to better show that the drug is safe and effective as a treatment for PTSD. The agency’s full reasons were shared only in a private letter to the company, but the advisory committee had previously expressed concerns about the drug. Missing data Adverse events, accusations of misconduct that put patients at risk, and concern Participants were informed whether they received the drug or a placebo.
This decision by the FDA is the first of its kind for a psychedelic drug, and it will likely only slow its formal introduction into mainstream medicine. schedule The agency has asked the FDA to reconsider. But even this initial rejection could signal a major shift in how researchers, drug companies and regulators treat a less understood and hotly contested part of psychedelic therapy: the therapy itself. For many advocates of psychedelics, the combination of therapy and drug has the greatest potential to change how the U.S. treats mental health. Friday’s rejection highlighted the difficulty of getting this combination approved by the drug-focused FDA. Now, some experts worry that approval depends on stripping out the therapy element and making psychedelics just drugs.
While many drugs work best when taken in a therapeutic context (such as antidepressants or psychotherapy), psychedelic therapy has traditionally mandated it. Intentionally combining mind-altering substances with talk therapy is thought to be safer and promote changes that drugs or therapy alone cannot induce. But the bulk of the research has focused on the effects of MDMA, psilocybin, and other psychedelic drugs, because the future of these substances depends on the FDA approving the drugs. That focus has left many questions about the therapy itself unanswered, ultimately complicating Lykos’ regulatory approval.
More time and careful research into the role of therapy in treating patients with psychedelics may lead the field to pinpoint what actually works and why. But Lycos’ initial failure may steer the field away from a therapy-focused approach altogether. “If I were running a pharmaceutical company that wasn’t interested in revolutionizing mental health care, I would take out the therapy element,” Stanford University neuroscientist Boris Heifetz told me. “I think it would be a shame, but it’s the least risky path to approval.”
Lycos’ MDMA-assisted therapy traces its origins back to the early days of psychedelic research, when mystical ideas about the nature of the self were mixed with science. The key idea of the therapy, designed to treat PTSD, is that humans have an inner wisdom or intuition and “may have a sense of how to move forward,” says Ingmar Gorman, psychologist and CEO of psychedelic therapy training organization Fluence. MDMA is thought to help unlock this inner wisdom by bringing up difficult experiences. Therapists try to let these experiences guide the sessions, but use their own intuition to help patients get through. They then help patients process the experiences in integration sessions. This general approach of helping therapists make sense of the often profound and difficult psychedelic journey underlies much of the promising psychedelic research to date.
But in nearly all of these studies, the role of talk therapy hasn’t been rigorously tested. It’s been held roughly constant between treatment and placebo groups to differentiate the effects of the drug. That’s important, of course, but a crucial part of the psychedelic drug equation is largely untested. These studies don’t tell us which elements of this complex, long-term therapy are actually helping patients. “That’s a problem,” Amy McGuire, a bioethicist at Baylor College of Medicine, told me. “The field doesn’t really understand the extent to which therapy contributes to the drug’s effects.” While Lycos’ data can’t answer this question, and the FDA doesn’t regulate the therapy itself, McGuire said, “they’re concerned about this therapy and they want to understand what role it’s playing.”
Patients Sometimes it gets worse Psychedelic drugs can cause intense and painful experiences. In the Lycos trial, three people who took MDMA said The Wall Street Journal Suicidal thoughts worsen during or after treatment Some patient Misconduct by therapists, including unwanted touching and restraints, has reportedly caused lasting psychological damage. Investigate all allegations Lycos has been arrested on suspicion of misconduct, and in one case filed a lawsuit against two therapists. Neche Devenot, a psychedelic drug researcher and bioethicist at Johns Hopkins University, argues that Lycos’s intuition-driven model puts patients at risk of harm and abuse. “They believe that if they take MDMA, they’ll be able to tolerate stress that they would normally not want to endure,” Devenot told me. While it helps some people overcome their illness, “I’ve also spoken to people whose symptoms have worsened because of it,” Devenot said. “The therapeutic component is important, and we need to stop and evaluate these models.”
Lykos’s treatment isn’t the only option for psychedelic treatment. Some researchers are exploring whether combining psychedelics with more traditional psychotherapies, such as cognitive behavioral therapy or acceptance and commitment therapy, could produce a therapeutic breakthrough. But again, there has been little rigorous research evaluating which parts of these therapies are most effective.
Maybe getting good results is all about a good relationship with your therapist, rather than the exactitude of the treatment method. Or maybe certain psychotherapeutic concepts, like questioning unhelpful core beliefs, prove especially important for certain groups. Understanding which parts of psychotherapy are necessary and which parts may be dangerous for different mental illnesses is crucial to ensuring that approved treatments work well in the real world, experts told me.
Some researchers hope that Lycos’ rejection will encourage other companies to do more rigorous studies. “This is an opportunity to better understand what we need from a psychotherapy perspective to maximize effectiveness,” McGuire told me. First, studies could include trials comparing treatment plans like Lycos’ non-directive approach with patients who get the drug with minimal intervention. Researchers could also compare different psychotherapy approaches—for example, CBT versus exposure therapy, while keeping the medication constant.
But testing psychotherapy is hard. “Different psychotherapies have a lot of common elements, so you need large samples to really discover the unique elements of each psychotherapy,” Jacob Aday, an experimental psychologist at the University of Michigan, told me. Such trials are quite time-consuming and expensive, given the many hours of care participants will undergo. Though trials may be valuable, companies have little financial incentive to invest that time and money, says Suresh Muthukumaraswamy, a neuropharmacologist at Oakland University. “You can’t patent conveying patterns of speech or behavior.”
Many companies with psychedelics in the regulatory pipeline are seeking to minimize treatment as much as possible. Compass PathwaysA London-based psychedelic start-up is promoting a model of psilocybin therapy that weakens the role of psychotherapy, calling it “psychological support.” MindMedThe US biotechnology company has received FDA breakthrough therapy designation for what it says is an LSD-based treatment for anxiety. No psychotherapy included“I expect biotech companies will tailor their offerings to meet the FDA’s specific regulatory requirements,” says Jules Evans, the agency’s director of regulatory affairs. A project to challenge the psychedelic experience“But that doesn’t necessarily translate to optimal care for patients,” he told me.
This simplified approach remains controversial in a field where many people hold strong beliefs that some form of intense therapy is truly important for lasting benefits. But if lighter therapies begin to show some benefit without the extra burden, they may come to dominate the market. That would undoubtedly help meet the enormous demand for new mental health treatments, but it could frustrate attempts to fully understand whether therapy is important and what forms it takes to be most transformative.
