The biggest unknown in psychedelic therapy is not the psychedelics

To the surprise of almost everyone involved, therapy using MDMA — commonly known as ecstasy — will probably not become legal this year. That’s because Lykos Therapeutics, the company trying to get it approved by the Federal Drug Administration (FDA), came under fire at a public hearing on June 4 over questions about whether MDMA plus therapy effectively treats PTSD and concerns about the safety of Lykos’s therapeutic approach. After researchers put the company on blast, the FDA’s advisory committee voted against approval, though a final decision will be made by the agency in August. There were lots of problems with the evidence about the drug itself. In Lykos’s clinical trials, participants who got MDMA experienced a significant reduction in their PTSD symptoms, doing better than those who got a placebo, but almost all the trial participants could tell which one they were getting. So, to what extent were those who got MDMA healing because they knew they were getting the real drug and expecting that it would help them? No one can tell. Regulators also weren’t sure if MDMA would harm the liver or cardiovascular system in the long term because Lykos didn’t gather evidence for long enough to know. And we don’t know about the drug’s addictive potential because Lykos failed to report on addiction-driving effects like euphoria; worse, some claim that Lykos pressured participants not to mention bad outcomes. While these are important issues, they may not by themselves have been enough to tank Lykos’s application. Concern about the placebo effect, for example, came up again and again, but it’s also come up in applications for other mental health drugs and it hasn’t stopped the FDA from approving those (think antidepressants). “What we know from other areas of clinical research is that expectancy alone doesn’t seem to have this robust an effect on PTSD,” Jacob Aday, a psychedelics researcher at the University of Michigan, told me. “I’d be very surprised if that's all that's going on here.” But there was another major question looming over Lykos (previously known as MAPS public benefit corporation, the biggest force pushing psychedelics toward legalization over the past few decades). It’s a question that had begun to bubble up in the news and which finally burst out at the FDA hearing: What the hell is going on with the “therapy” part of Lykos’s “MDMA therapy”? Therapy is not just one practice — there are many different approaches, from psychoanalysis to exposure therapy. Yet, even as researchers enthuse about the therapeutic potential of psychedelics, there’s been shockingly little research into which kind of therapy should be paired with the drugs, in part because the psychedelic industry has little financial incentive to study that. “The drugs have been manipulated many times across studies, but the studies have not manipulated the therapy component at all,” Aday said. “That's problematic. This is considered a combined drug-therapy treatment, and so far we've only evaluated 50 percent of that equation.” Some types of therapy, like cognitive behavioral therapy, have plenty of evidence to back up their effectiveness when used on their own. Others, not so much. Lykos favors certain therapy modalities that have less of an evidence base and more of a New Age flavor. Some prominent critics have said Lykos’s approach leads to foreseeable harms for patients, to the point that they argue Lykos qualifies as a “therapy cult.” What is the “therapy” part of MDMA therapy? If you look at Lykos’s publicly accessible treatment manual, you’ll see that one idea comes up again and again: that each person has an “inner healing intelligence, which is a person’s innate capacity to heal the wounds of trauma.” This idea is core to Holotropic Breathwork and Internal Family Systems — two modalities that arguably form the backbone of Lykos’s therapy model. Holotropic breathwork is the brainchild of psychiatrist Stanislav Grof. He was an early advocate of psychedelics, but once President Richard Nixon kicked off the “war on drugs” in the 1970s, Grof had to figure out another, drug-free way to induce altered states of consciousness. Like many an ancient meditator before him, he found that intense breathing techniques can trigger something akin to a psychedelic trip. He argued that this kind of experience can mobilize “an inner radar” that finds traumatic material buried in the psyche so it can then be processed. There’s no question that Grof (and his wife Christina, another major figure in the field) influenced Lykos profoundly. “The foundation for this therapeutic approach was laid by Stan and Christina Grof,” among others, says the treatment manual. The idea that we each have an “inner healing intelligence” is also key to Internal Family Systems (IFS), an approach developed by therapist Richard Schwartz in the 1980s. IFS says that the psyche is made up of different “parts,” which try to protect us in different ways. Some ways may be maladaptive in the long run — like a part that says “let’s get drunk so we won’t have to think about the traumatic thing we experienced” — but the parts are just doing their best in the moment to help us maintain emotional stability. IFS also posits that we each have a wise inner “Self,” which embodies eight C’s: clarity, compassion, calmness, confidence, curiosity, connectedness, creativity, and courage. The Lykos treatment manual makes clear its intellectual debt to IFS. “One way to describe the effects of MDMA is that it facilitates access to a high level of Self-energy, and thereby brings courage to face painful experience and provides clarity and compassion for one’s own parts,” it says. You might be thinking: So what? Many people feel like they do have a core self, and if that idea helps them heal, why not embrace it? “Inner Healing Intelligence is not mystical or domineering, it is the opposite,”Jamie Beachy, a therapist on the Lykos study, told me by email. She said it’s about “recognizing and trusting a participant’s inner capacity while providing the right conditions through therapy to facilitate this healing process, including a trusting therapeutic relationship.” Trusting a participant’s inner capacity sounds positive, and in the right therapist’s hands, it could be a refreshing change to more mainstream, biomedically informed styles of therapy that tend to pathologize the patient. But the helpfulness of the “Self” or “inner healer” idea may depend on whether we embrace it as a useful metaphor or as a literal reality. We don’t have scientific evidence that this core self exists; dissect a human brain and you will find lots of different parts carrying out different functions, but you won’t find a unitary guiding persona. Yet Lykos’s therapy model takes this self quite literally, and critics say the company’s rigid focus on the concept has actually enabled harm. Nese Devenot, a Johns Hopkins University researcher specializing in psychedelic bioethics, told me the inner healer concept can yield a “flawed model of consent” — one that could lead therapists to misconstrue what a patient truly wants, or worse, engineer artificial consent. When a trial participant says something in the course of therapy — like “no” or “stop” or “it hurts too much” — is there a reliable way for the therapist to know whether that’s coming from the wise “inner healer” or from a “part” that’s resisting the therapy, perhaps because therapy can be scary and the part is trying to help the person maintain emotional stability? According to the Lykos manual, “therapists should trust that any fear, memories, etc. that keep coming up are doing so to be healed ... and that the participant’s psyche/inner healer knows when the best time is for this to occur.” It adds that “surrendering” to the inner healer “may be the method of therapeutic action that is so hard to come by without the help of MDMA.” But it’s easy to see how this could go awry, especially when you consider the fact that MDMA is known to enhance suggestibility, making the patient more trusting and less equipped than usual to say no. Maybe a traumatic memory isn’t surfacing because the psyche knows now’s the moment for that trauma to be healed. Maybe the person is just triggered. And maybe they’re triggered by something the therapist is doing to them. In one case, therapist Veronika Gold touched a patient, Annie, who became distressed and physically struggled against her. Gold was not troubled. She writes in a book on psychedelic therapy: “Annie began to add her voice, expressing anger and saying, ‘Go away! Get your fucking hands away from me!’ The words were clearly meant for her father and did not indicate that she wanted me to go away or stop. Because we had the agreement to use the specific safe word “enough” if she wanted me to stop the touch, there was no confusion in my mind about how to proceed. Over the course of the next several minutes, she pushed my hands with increasing vigor and force.” Bear in mind that someone under the influence of MDMA might not remember a safe word, especially if they’re in the midst of a panic attack. “Phase 3 therapists were trained on the sensitive nature of consent,” a Lykos Therapeutics spokesperson assured me. “Patients at any time could withdraw consent to appropriate therapeutic touch such as hand holding.” But that doesn’t seem to have been the case for Annie, nor was it the case for Meaghan Buisson, a participant in phase 2 of the study. In 2015, Buisson — a sexual assault survivor who came in the hope of healing her PTSD — was pinned down and cuddled by her therapists, a married couple. Video footage shows the therapists continuing to touch her even after she reacts with distress. Later, the male therapist had sex with Buisson; in a lawsuit, she alleged that it was sexual assault. MAPS said the married therapists “substantially deviated” from the treatment manual, and it cut ties with the couple. But Devenot, who credits psychedelics with saving her own life and who previously volunteered with MAPS, told me that this isn’t just about a couple of bad apples. “There's an emphasis on the guide's ability to cultivate the spiritual authority to discern when a participant needs to hurt,” she said. Notably, the treatment manual permits two kinds of touch: “nurturing touch,” such as holding a patient's hand or patting them on the back, and “focused bodywork,” which involves giving the patient some resistance to push against. This gives therapists an unusual amount of latitude. Touch isn’t a feature of traditional talk therapy, and it’s controversial in the world of MDMA-assisted therapy, especially because there’s a history of sexual abuse in the psychedelic subculture. Taken together, all this means that therapists could wittingly or unwittingly feed their own thoughts or desires to a patient, then pass them off as the patient’s true wishes. If the patient complies, the Lykos logic enables the therapists to read that as the wise self talking. In fact, they can view themselves as getting the most authentic consent possible since the premise is that a patient is more able to access the true self during an MDMA trip than during regular life, when mental health issues obfuscate that inner wisdom. And if the patient resists? The therapists can just interpret that as a fearful “part” acting up. At its worst, the logic forms a tight, self-confirming loop, one that could increase risks to the patient rather than minimizing them. Is Lykos a “therapy cult” for MDMA? “I submit that Lykos is a therapy cult that uses the application under review to further mystical and utopian goals,” Brian Pace, who teaches psychedelic studies at The Ohio State University, told the FDA advisory committee. “This lens explains the mounting allegations against them regarding research misconduct and clinical trial participant harms.” Devenot, the Johns Hopkins bioethicist, uses the same term — “therapy cult” — to describe Lykos, saying, “therapy cults transform therapeutic and personality theories into totalizing ideologies that promise reductive solutions for diverse causes of psychological distress.” Former Lykos employees have also expressed the view that the company is a cult, citing, for example, its use of techniques from hypnosis and neuro-linguistic programming (a scientifically unsupported method for changing someone’s thoughts) when trying to get people to donate money to the company. “Half the company was like, ‘Oh, this is so inspiring,’ and the other half is like, ‘Jesus Christ, is this a cult?’” one ex-staffer told Insider. The health news site STAT also quotes a former Lykos employee describing “cult-like dynamics” at the company, and another saying, “The more we tried to make it a scientific company, the more we got disparaged by the cult side.” In an emailed statement, the Lykos spokesperson told me that allegations of cultishness “discredit the scientific rigor and evidence-based approach that has been taken to develop a new potential option for the millions of people who are suffering with PTSD.” She added that “the concept of the ‘inner healing intelligence’ does not refer to a spiritual concept” and that the therapy uses a “conceptual framework that centers the participant’s autonomy and self-directed healing which a skillful therapist seeks to amplify in this approach.” In academic religious studies, scholars have moved away from the pejorative term “cult,” preferring “new religious movement.” That’s because there’s often little separating a cult from a religion other than the passage of time: plenty of faiths, like Christianity, could have been viewed as cults at the outset but gained the status of legitimate religions as they became more dominant. To some degree, the distinction is in the eye of the beholder. Nevertheless, in the cult studies literature, scholars have used the term “psychotherapy cult” to describe practices that share some core similarities, like precluding doubt or criticism and encouraging members to see themselves as heroes who are enlightening humanity in the face of great resistance. We’ve already covered how the Lykos logic could be used to preclude doubt in patients. Former employees have also said that the company pushed ideological conformity. “The longer I was there,” one told Insider, “the more it was like, you need to agree with this, or you’re out.” According to the Institute for Clinical and Economic Review, a nonprofit evaluating new medical treatments, trial participants have said they were told that they were helping make history and not to talk about adverse events because that could hurt MDMA’s chances of approval. Rick Doblin, who founded MAPS in 1986, has often suggested that psychedelics could save humanity. It’s a utopian view that echoes Grof’s spiritual vision, as Doblin acknowledged in a paper: “We'll set up a network of MAPS clinics. And other people will be able to do this as well. Then we'll have world peace, but it might take a little bit of time between those. All of this really comes back to Stan Grof ... And we are coming forward to fulfill the promise.” Doblin says his ultimate goal is for psychedelics to lead to “a spiritualized humanity” and “net-zero trauma by 2070.” In 2019, he spoke on the TED stage about how his own experiences with psychedelics gave him the feeling that they could “help be an antidote to tribalism, to fundamentalism, to genocide, and to environmental destruction.” Concluding his talk, Doblin said: “Humanity now is in a race between catastrophe and consciousness. The psychedelic renaissance is here to help consciousness triumph.” The declaration has the feel of apocalyptic logic. Found in many religious traditions, apocalypticism warns that catastrophe is looming and that humanity needs a tool to achieve salvation. It’s a part of eschatology, the branch of theology that deals with the “end times” or the final destiny of humanity. [Image: Rick Doblin founded the Multidisciplinary Association for Psychedelic Studies in 1986. https://platform.vox.com/wp-content/uploads/sites/2/2024/06/doblin-GettyImages-94859476_9ae52f.jpg?quality=90&strip=all] Although lots of companies talk about their work in terms of changing the world, few executives go around implying that their drug is “the antidote to Hitler” or the path to Israeli-Palestinian peace, as Doblin has done. The philosopher Isaiah Berlin once wrote in his critique of all utopian projects: “To make mankind just and happy and creative and harmonious forever — what could be too high a price to pay for that? To make such an omelet, there is surely no limit to the number of eggs that should be broken.” That’s exactly what worries Lykos’s critics. Why hasn’t there been more research into the therapy? In an ideal world, we’d have studies pitting different types of therapy against each other in combination with MDMA to see which works best, said Aday, the University of Michigan psychedelics researcher. But running psychotherapy studies is even harder than running drug trials. “You very rarely see two psychotherapies pitted against each other in a randomized controlled trial,” Aday told me. “That's because there's so many common factors among different therapies that you need to have a super large sample to actually test one therapy against another and get meaningful results.” It’s also really expensive to get a large enough sample to run combined drug-therapy trials. Each participant has to be screened for a host of medical and psychological conditions, and it can cost $50,000 to enroll just one person, Aday said. Well-powered studies comparing psychotherapies often have at least 100 to 200 participants, which means you can easily run up a $5-$10 million bill to conduct a psychedelic-assisted psychotherapy study. So far, there’s been almost no federal government support for psychedelic-assisted therapy studies, a possible hangover from the fact that drugs like MDMA are still classified as illegal. In 2022, there was zero federal funding; since then, one study has been funded. That means most of the funding has had to come from industry or philanthropy. And there's a simple reason industry isn’t interested in funding studies that look at therapy: “They're not going to make any money off of that,” Aday said. “You can’t patent psychotherapy.” Among philanthropists, there may also be a feeling that the drug, not the therapy, is the exciting new thing. “This plays into the general biological reductionism that's kind of dogma right now, that if you can take a pill and make it go away, that's much preferred than actually going through something experientially or doing lifestyle changes,” Aday said. But the fact that the therapy component of MDMA therapy is so understudied is a major problem. “Most of the harms that I’m seeing are tied to the therapy,” not the drug, Devenot said. “This is a new treatment modality,” said Balázs Szigeti, a University of California San Francisco researcher who investigates psychedelics and their relationship to the placebo effect. “It’s not therapy. It’s not a drug. It’s therapy with a drug. It doesn’t fit into either category and that’s why it’s a little confusing” to the FDA. That agency is set up to evaluate drugs; before the Lykos case, it had never attempted to evaluate therapy. “The difficult thing ... is that we don’t regulate psychotherapy, and also we don’t really have any say in the design or the implementation of the particular therapy that is going to be used,” the FDA’s Tiffany Farchione said at the hearing. With psychedelic treatments, the therapy component seems to be key to healing, so we should expect to see a growing number of applications for combined drug-therapy treatments — and that means the FDA itself may need to change. “It would be useful for them to develop a specialized unit, possibly in collaboration with the American Psychological Association or other leading psychotherapy organizations, to evaluate these submissions,” Aday said. If that happens, it’s likely to take a while; the FDA is not an agency known for its speed. As Szigeti said, “It’s going to be difficult to recognize that this is something different here requiring different processes,” from adjusting the expectations around placebo effects in psychedelic trials to developing a more rigorous therapy protocol. “MDMA made first contact” with the FDA, Szigeti told me. “But the same questions are going to be raised about LSD, about psilocybin. It’s coming.”