The U.S. Food and Drug Administration (FDA) has issued a complete response letter for MDMA-assisted psychotherapy (MDMA-AT) for treating post-traumatic stress disorder (PTSD), requesting an additional phase 3 trial to further evaluate its safety and efficacy. This decision, as reported by Psychiatric Times, temporarily halts what could have been a groundbreaking approval for the treatment of PTSD using MDMA, also known as methylenedioxymethamphetamine.
Despite this setback, Lykos Therapeutics, the company developing the MDMA-AT treatment, remains resolute. Lykos expressed confidence that the FDA’s concerns could be addressed using existing data, post-approval requirements, or referencing scientific literature. Ongoing discussions between the company and the FDA are aimed at establishing a clear path forward for the treatment.
While the future of MDMA-assisted therapy is temporarily uncertain, several other psychedelic treatments are steadily advancing through clinical trials. Atai Life Sciences, for example, recently announced promising results from a phase 1b trial of VLS-01, a buccal film formulation of N,N-dimethyltryptamine (DMT), for treatment-resistant depression (TRD). The next phase 2 study is expected to begin by the end of 2024, focusing on safety, efficacy, and the durability of response.
Numinus Wellness is also making significant strides in the psychedelic space with their studies involving Cybin’s CYB003, a deuterated psilocybin molecule designed for treating moderate to severe depressive disorders. Meanwhile, Compass Pathways is testing COMP360, a synthetic form of psilocybin, which has shown promising early results in treating PTSD. These developments highlight the continued push toward psychedelic-assisted therapies for a wide range of psychiatric conditions.
Progress is also being made with LSD and ketamine-based therapies. MindBio Therapeutics has shown promise in phase 2a trials for major depressive disorder (MDD) with MB22001, a titratable microdosing form of LSD. They are also investigating LSD’s potential for treating conditions like premenstrual dysphoric disorder and depression associated with cancer. MindMed is progressing with their own LSD compound, MM-120, which has shown potential for treating generalized anxiety disorder (GAD), with a phase 3 trial scheduled to begin this year.
Ketamine-based therapies are also advancing, with Awakn Life Sciences leading the charge in addressing alcohol use disorder. Their MORE-KARE phase 3 trial is underway, testing the efficacy of ketamine infusions combined with psychosocial support.
As the psychedelic field expands, all eyes are on Lykos Therapeutics as they navigate the FDA’s requirements for MDMA-assisted psychotherapy. The company has undergone a significant reorganization, including a 75% reduction in workforce, and appointed Dr. David Hough as senior medical advisor to guide the next phase of clinical work. Dr. Hough brings extensive experience in psychiatric drug development, having led successful projects such as Spravato. Rick Doblin, PhD, founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), has stepped down from Lykos to focus on public advocacy for global access to MDMA and other psychedelics. Doblin’s resignation from the Lykos Board comes as the company continues its dialogue with the FDA.
Despite the challenges facing MDMA-assisted psychotherapy, the field of psychedelic research remains vibrant. With more than 185 clinical studies on psilocybin, 104 on MDMA, and 58 on LSD ongoing according to clinicaltrials.gov, the future holds promise for these novel treatments. As companies continue their work, patients and researchers alike are hopeful that these therapies will become more widely available in the near future.
