Therapy
By Elena Schmidt
Lykos’ psychedelic-assisted therapy model was meant to reinvent mental healthcare as we know it. Its PTSD protocol, which included preparation support, three guided MDMA therapy sessions, and integration counseling, took a bold step toward merging pharmacology with psychotherapy. But the FDA’s decision to reject it may force the psychedelic industry to pivot from resource-intensive and holistic to streamlined and pharma-friendly.
How We Got Here: Understanding the FDA’s Rejection
On Aug. 9, Lykos announced that the U.S. The Food and Drug Administration (FDA) rejected its new drug application (NDA) for MDMA-assisted therapy for PTSD. The company’s press release was so matter-of-fact and measured that I had to read it twice to grasp the meaning.Eventually, my eyes refocused on two sentences: “The FDA communicated that it had completed its review of the NDA and determined that it could not be approved based on data submitted to date. The FDA has requested that Lykos conduct an additional Phase 3 trial to further study the safety and efficacy of midomafetamine (MDMA).”Lykos has not shared the FDA’s complete response letter (CRL). However, it said the agency rejected its NDA for reasons aligning with the June 4 Psychopharmacologic Drugs Advisory Committee (PDAC) hearing. I’ve investigated the infamous MDMA hearing in prior articles, so I’ll spare the exhaustive details here. But to briefly recap, PDAC members who lacked psychedelic expertise said that Lykos’ statistically significant clinical data was unreliable. It determined the trials contained inherent design flaws and feared that alleged misconduct, although unsubstantiated, could have skewed the data. Nine of eleven panelists said the NDA was not ready for approval. PDAC’s vote confused many advocates, who noted that Lykos followed the FDA’s draft psychedelic therapy FDA approval guidance. Others pointed out that MAPS and the FDA co-created the trial design through a Special Protocol Assessment in 2017. In the FDA’s words, “We have completed our review and, based on the information submitted, agree that the design and planned analysis of your study adequately address the objectives necessary to support a regulatory submission.”Dr. Scott Shannon, Principal Investigator in MAPS Phase 2 and 3 clinical trials, added that the FDA thoroughly investigated MAPS’s research sites during the trials to ensure proper data acquisition.However, the advisory committee ignored these facts. Instead, they lamented over Lykos’ drug plus psychotherapy protocol, consistently questioning its validity and whether emotional support was even necessary alongside MDMA to alleviate PTSD. Worse, despite blatant contrary evidence, they asserted that MAPS’ FDA-aligned MDMA therapy protocol could do patients more harm than good.
Facing the Fallout: Lykos’ Next Steps
Lykos must now conduct a third Phase 3 clinical trial to overcome issues it thought were ironed out. The new trial will take at least two years and cost millions of dollars the team may not have. In preparation, Lykos laid off 75% of its workforce, discontinued funding MDMA therapy research in Europe, and radically shifted its leadership team.Rick Doblin, PhD, founder of Lykos’ non-profit parent company MAPS, resigned from the board shortly after the MDMA therapy FDA rejection. Doblin, a beloved psychedelic trailblazer and somewhat controversial figure, said his activist nature interfered with Lykos’ regulatory path. He will now pursue MAPS’ broader research, education, and policy reform goals. Upon Doblin’s departure, Lykos hired a seasoned pharmaceutical executive, Dr. David Hough, to oversee the NDA’s next steps. In a recent press release, Lykos Chairman Jeff George said, “Dr. Hough is a consummate industry professional and exactly the right person to lead the crucial work of engaging with the FDA for our resubmission.”Hough’s resume includes bringing Spravato (esketamine nasal spray) to market at Johnson & Johnson, where he led compound development and the medical, scientific, and regulatory processes.Spravato is a ketamine-analog medication with dissociative psychedelic properties prescribed for major depressive disorder. The FDA approved Spravato’s NDA in 2019 with a protocol requiring patients first to prove that traditional antidepressants failed before becoming eligible for coverage. Glaringly, Spravato’s application did not include therapeutic intervention, begging the question, could Hough have similar plans for MDMA?
A New Path for Psychedelic Therapy?
The future of psychedelic-assisted therapy remains uncertain. Doblin, among others, believes that Lykos will eventually bring MDMA therapy to the masses, but following the FDA rejection, he has grave concerns about the direction the industry might take.On a recent Modern Enlightenment podcast by Ceremonia, he expressed fears that the FDA’s decision could have a chilling effect on future psychedelic NDAs, setting a hands-off precedent he deems immoral.Doblin told Ceremonia, “We (MAPS) had suggestions that it might be interesting to do a study just giving people MDMA without any support, but Michael Mithoefer, our lead psychiatrist, myself, and others thought it would be unethical to do that.”“…stuff comes up [on MDMA], and if you’re not capable of processing it, you can end up worse off,” he added.Doblin also articulated why he believes MDMA alone is insufficient to extinguish PTSD.He explained that 40% of Lykos’ clinical trial participants had previously tried MDMA recreationally before joining the study. If the drug alone were all they needed, these patients would’ve been cured of PTSD. But they weren’t. Many had suffered for years without relief. And it was the combination of MDMA plus psychotherapy that finally helped them achieve remission.Doblin explained, “It’s not about the drug. It’s about how you process. And it also is not just about the drug experience. It’s about integration. It’s also about preparation. All of that is what contributes to the outcomes.” In other words, the idea that a psychedelic experience alone can cure mental health issues ignores the complexities of trauma and the human psyche.Nevertheless, the FDA skepticism about MDMA therapy means psychedelic NDAs may start to look like Spravato’s, or they may follow the “psychological support” approach that pharmaceutical companies Compass Pathways (Compass) and Mind Medicine (MindMed) are promoting. “Profit-oriented companies like Compass are minimizing any psychotherapeutic angle. They just want [psychedelic medicine] to fit into the psycho-pharm model that people understand,” said Shannon.He added, “I have to tell you that 95% of the people that I know in the psychedelic realm don’t believe in that {approach},” he added.According to Shannon, “psychological support” means licensed therapists are on-site during drug administration. But instead of providing counseling intervention, they serve in more passive roles, stepping in only to prevent psychological harm when necessary.“[This approach comes from] people stuck in the old ways. People who want something comfortable and not challenging. This is what fading, failing paradigms do. They try to prevent new ideas from coming in,” said Shannon.
Will Lykos Carry MDMA Therapy to the FDA Finish Line?
Lykos has vowed to bring this novel psychedelic medicine to the current regulatory framework. However, industry insiders think its new Phase 3 trial will introduce different study design elements that could render the original protocol unrecognizable.At the very least, Lykos may need to shift from integrative, holistic therapies, like Internal Family Systems, Hakomi, and Holotropic Breathwork, to accepted “evidence-based approaches” like Cognitive Behavioral Therapy (CBT) that fit neatly into the traditional medical structure. CBT can be effective for PTSD, but today’s mental health crisis proves it is remarkably substandard.Amid the tug-of-war between innovation and convention, I fear psychedelic-assisted therapy, as we now know it, may be headed toward extinction. But I won’t mourn its passing. Instead, I’ll see this phase as a metamorphosis—where the old form dissolves, making way for a model that adapts to today’s framework while (hopefully) preserving the transformative essence of psychedelic healing.
