FDA to consider ‘innovative approaches’ to psychedelic drug development
Top US Food and Drug Administration (FDA) officials said the agency is open to novel, “innovative approaches” to the clinical development of psychedelic drugs in light of the worsening mental health crisis in the US.
The agency’s evolving approach to psychedelic drugs was presented in a New England Journal of Medicine (NEJM) article published on Wednesday. The article was written by top officials from the agency’s Center for Drug Evaluation and Research (CDER), including Michael Davis — who was appointed as CDER’s permanent director earlier this week — Teresa Buracchio, director of the Office of Neuroscience within the Office of New Drugs at CDER, as well as Tiffany Farchione and Bernard Fischer, who lead the Division of Psychiatry within the Office of Neuroscience. (RELATED: FDA names permanent CDER, CBER directors, new deputy commissioner for AI, Regulatory Focus 9 September 2026)
The article follows the publication of FDA’s final guidance laying out considerations for clinical investigations of psychedelic drugs, which was released in July, three years after the agency issued a draft version for comment. (RELATED: Psychedelics: FDA offers clarifications, compromises in final clinical trial guidance, Regulatory Focus 13 July 2026)
The officials noted the prevalence and significant economic burden of mental health disorders, like major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and acknowledged that existing treatments may not benefit all patients.
“[FDA] recognizes that although some people benefit from available treatment options, for others our current medications are not enough,” they wrote. “The FDA is committed to meeting this moment with the urgency it deserves. Through innovation and by leveraging existing programs, we can begin to address the unmet need for new and better treatments.”
The authors note that the agency has granted breakthrough therapy designation to several psychedelic drugs, which enables “more intensive guidance from the FDA” and more frequent opportunities to meet with officials, as well as the potential for a rolling review. These investigational drugs include Definium Therapeutics’ LSD-derivative DT120, which recently received its second breakthrough designation, and Cybin Inc’s CYB003, a deuterated psilocybin analog.
So far, the agency has yet to approve any psychedelic drugs for any indication, and in 2024, the agency rejected Lykos Therapeutics’ (now Resilient Pharmaceuticals) MDMA-assisted therapy for PTSD, years after granting it the first breakthrough therapy designation for a psychedelic drug in 2017.
The officials touted the recently issued final guidance as offering a flexible approach to psychedelic drug development.
“The guidance builds on the agency’s experience with drug development programs and incorporates relevant input from the scientific and patient community to address the distinct methodologic challenges in psychedelic clinical trial design — particularly issues around blinding, selection of control, and assessment of the durability of treatment effects,” they wrote.
Unblinding poses is a significant challenge to traditional placebo-controlled trials in this space, as the “pronounced and recognizable” treatment effects can cause both patients and investigators to become “functionally unblinded” during the study. As such, the officials said that FDA is open to approaches that rely on an active comparator instead of an inert placebo to help mask whether participants are taking the investigational drug or not or comparing the study drug to a lower dose.
However, they noted that FDA may still expect to see a placebo-controlled trial, as a comparison to an inactive placebo can help determine whether adverse events are caused by the investigational drug.
The officials also noted that the agency is also open to approving psychedelics for intermittent or as needed use. “The FDA is receptive to granting initial approval based on evidence of efficacy over a clinically meaningful duration (e.g., 12 weeks), in conjunction with a longer-term preliminary assessment of the need for and safety of treatment with additional doses (e.g., continuing blinded follow-up for 12 months),” they wrote, adding that questions about dose interval and continued efficacy could be addressed after approval.
Due to the risks posed by these drugs, the officials said that a risk evaluation and mitigation strategy (REMS), potentially featuring elements to assure safe use (ETASU), and additional postmarketing studies may be required for approval.
