FDA Rejection of Lykos' MDMA Therapy Sparks Debate on Psychedelic Drug Approval Process

The pharmaceutical industry is grappling with new challenges in the emerging field of psychedelic therapies, as evidenced by the recent rejection of Lykos Therapeutics' MDMA-assisted therapy for post-traumatic stress disorder (PTSD). The FDA's complete response letter (CRL), made public in September 2025, has ignited discussions about the regulatory pathway for psychedelic drugs and the future of mental health treatments.

Lykos Faces Setback in MDMA Therapy Approval

Lykos Therapeutics, recently rebranded as Resilient Therapeutics, received a CRL from the FDA in August 2024, following a 10-1 advisory committee vote against recommending approval of their midomafetamine (MDMA)-assisted therapy for PTSD. The rejection letter, now public, cites concerns including unreported safety events, potential for drug abuse, study design issues, and questions about the durability of the treatment's effects.

Rick Doblin, founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) and Lykos, expressed frustration with what he perceives as a "changing of the goal posts" in the regulatory process. Doblin highlighted that the FDA did not consider an amendment submitted by Lykos addressing concerns raised during the advisory committee meeting, stating, "Those responses from the company were not considered in this complete response letter."

Regulatory Challenges and Industry Implications

The FDA's rejection has raised questions about the criteria for approving psychedelic therapies. Doblin argued that the requirement for demonstrating durability of effect beyond 18 weeks is inconsistent with standards applied to other drugs, including cancer treatments and Johnson & Johnson's esketamine therapy, Spravato.

The CRL's recommendation for a new randomized, double-blind study to address durability concerns has also sparked debate. Doblin highlighted the complexities of blinding studies for psychedelic drugs, noting that even for SSRIs, "the double blind fails to work anyway" due to noticeable side effects.

This development has significant implications for the broader psychedelic therapy industry. Doblin cautioned against what he sees as a misinterpretation of the FDA's message, stating, "The for-profit psychedelic industry has got the wrong message." He emphasized that the focus should remain on patient outcomes rather than minimizing the role of psychotherapy in mental health treatments.

As the industry navigates these regulatory challenges, the outcome of Lykos' MDMA therapy application may set important precedents for future psychedelic drug approvals. The pharmaceutical sector will be closely watching how regulators and companies address the unique aspects of psychedelic-assisted therapies in the coming months and years.