On June 23, 2023, FDA issued a first-of-its-kind draft guidance for sponsors of studies of psychedelic drugs. The guidance arrived just as the Psychedelic Science 2023 conference in Denver was wrapping up. Touted as the “largest psychedelic conference in history,” the conference drew over 12,000 people, including an array of medical professionals, government officials (i.e., Dr. Joshua Gordon, Director of the National Institute of Mental Health (NIMH), and Commander Gene Gunn in FDA’s Office of Regulatory Affairs) and politicians (i.e., Colorado Governor Jared Polis and former Texas Governor Rick Perry). Additionally, recent activity on Capitol Hill demonstrates a growing interest by legislators in the field of psychedelic science. These events signal a significant shift in our cultural awareness and acceptance of psychedelics and their potential to address an array of medical conditions.

In recent years, there has been a growing interest in better understanding how psychedelic drugs could be used to address mental and behavioral health conditions like post-traumatic stress disorder (PTSD), anxiety and depression. As FDA notes in its draft guidance, examples of “classic psychedelics” include psilocybin, lysergic acid diethylamide (LSD) and 3,4-methylenedioxy-methamphetamine (MDMA). Two companies that were featured prominently at the Psychedelic Science conference are in the process of conducting phase 3 clinical testing of certain psychedelic drugs and have received FDA designation as “Breakthrough Therapies.” The Multidisciplinary Association for Psychedelic Studies’ Public Benefit Corporation (MAPS PBC) is studying MDMA for PTSD. COMPASS Pathways is studying a synthetic formulation of psilocybin, “COMP360,” in treatment-resistant depression. Other psychedelics are being studied and showing promise as “potential treatments for mood, anxiety and substance use disorders,” according to FDA.  

The newly released draft guidance differs from more traditional FDA guidances because of the “emerging” nature of this area of drug development and the “limited experience as to the configuration of programs that may support approval of a psychedelic drug.” FDA states that instead of providing “specific recommendations on study design,” the draft guidance will “present foundational constructs that all sponsors, including academic sponsor-investigators, studying the therapeutic potential of psychedelic drugs should consider.”

The draft guidance is intended to illuminate the “unique challenges” associated with clinical studies of psychedelic drugs. Many psychedelic drugs are subject to additional regulation by the Drug Enforcement Administration (DEA) as Schedule I substances under the Controlled Substances Act if DEA has determined that the drug has high abuse potential and a lack of currently accepted medical use in the United States. Furthermore, to meet FDA’s effectiveness standard, adequate and well-controlled clinical studies using a design that “permits a valid comparison with a control” to assess a drug’s effect are generally required. But in the context of psychedelic drugs that often prompt “intense perceptual disturbances,” reliance on a “traditional placebo as a control” might be “problematic.” The guidance also walks through considerations relating to the potential for serious adverse effects and the need for different monitoring and staffing models to address risks that could jeopardize patient safety.

Capitol Hill has also taken note of the growing body of evidence demonstrating the promise of psychedelics. FDA’s draft guidance was issued two days after the introduction of a bill (H.R. 4242) that would require FDA to “issue guidance on considerations for conducting clinical trials for psychedelic assisted therapy.” Earlier this year, the Congressional Psychedelics Advancing Therapies (PATH) Caucus was relaunched with a goal of addressing “ways to alleviate the national mental health crisis through psychedelic science and research.” Late last year, Senators Cory Booker (D-NJ) and Rand Paul (R-KY) introduced the bipartisan “Breakthrough Therapies Act,” which seeks to alleviate the burdens of conducting research on Schedule I substances “such as MDMA and psilocybin.” And this is only a sampling of recent legislative activity in this space.

Much remains to be learned as research in this burgeoning field continues. But the fact that FDA took the initiative to lay out its thinking in a draft guidance at this relatively early stage underscores the agency’s commitment to fostering a climate of responsible development of these products. FDA is accepting comments on the guidance until August 25, 2023—a key opportunity for those engaged in this area of drug development or considering entering it to provide feedback to FDA as it continues to assess new and emerging products.