Guidance Issued by FDA for Psychedelics Clinical Trials

The US Food and Drug Administration (FDA) has released new draft guidance that focuses on important factors for researchers conducting clinical trials involving psychedelic drugs for the treatment of medical conditions. This marks the first time the FDA has provided guidance for studying psychedelics like psilocybin, LSD, and MDMA, which have shown potential as treatments for severe mental health conditions. The guidance covers considerations for trial conduct, data collection, subject safety, and new drug application requirements throughout the drug development process.

In a statement, Dr. Tiffany Farchione, the director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, acknowledged that psychedelic drugs exhibit initial promise as potential treatments for mood, anxiety, and substance use disorders. However, she emphasized that these drugs are still being investigated and that sponsors evaluating their therapeutic potential should consider their unique characteristics when designing clinical studies.

Psychedelics for Mental Health

Growing interest in the therapeutic potential of psychedelics has prompted research into the use of these drugs as treatments for medical conditions such as depression, anxiety, substance misuse disorders, and post-traumatic stress disorder (PTSD). Early studies have shown promise, and the FDA has designated psilocybin and MDMA as “breakthrough therapies,” indicating that clinical evidence suggests they represent significant improvements over standard treatments for certain medical conditions.

However, the FDA noted that studying psychedelics presents unique challenges that require careful consideration. The guidelines were developed to advise researchers on study design and other considerations as they develop medications containing psychedelics, including “classic psychedelics” like psilocybin and lysergic acid diethylamide (LSD), which typically act on the brain’s serotonin system, as well as “entactogens” or “empathogens” like methylenedioxymethamphetamine (MDMA).

The FDA highlighted that many psychedelic drugs produce psychoactive effects that may make them susceptible to misuse. The guidance also acknowledges that research into Schedule 1 drugs such as psilocybin is subject to stricter controls and must comply with requirements set by the Drug Enforcement Administration (DEA).

The FDA stated, “The evidentiary standard for establishing the effectiveness of psychedelic drugs is the same as for all other drugs. However, there are unique factors investigators may need to consider when designing their clinical trials if those trials are to be considered adequate and well-controlled.” The draft guidance also addresses the role of psychotherapy in psychedelic drug development, considerations for safety monitoring, and the importance of characterizing dose-response and treatment effect durability.

Positive Feedback from Lawmakers

Only a few days before the FDA issued draft guidance on researching psychedelic drugs, a bipartisan group of lawmakers in the US House of Representatives introduced legislation to direct the agency to take action in this area. The bill, H.R.4242, was filed on June 21 by Rep. Dan Crenshaw (R-TX), Rep. Mariannette Miller-Meeks (R-IO), and California Democratic Rep. Ro Khanna. If passed, it would require the Secretary of Health and Human Services, in collaboration with the FDA, to release guidelines for research into medical conditions including PTSD and traumatic brain injury. After the guidelines were released, the lawmakers who introduced the bill commended the FDA for taking this step.

Rep. Miller-Meeks, a medical doctor, stated on June 30, “Many veterans find guided use of psychedelics with assisted therapy as a way to successfully treat the excruciating post-traumatic pain they face, with better outcomes and fewer medication side effects. As a physician, I know the importance of medical research, and I am encouraged by the FDA’s support and guidance regarding psychedelic clinical trials. This important step gives our veterans another option and hope when they feel they’ve run out of coping methods.”

Rep. Crenshaw added, “I’m glad the FDA is taking this first step of issuing guidance for psychedelic clinical trials and listening to my bipartisan legislation with Reps. Miller-Meeks and Khanna. It’s critical that we get this right for the researchers conducting this important scientific work. We need this guidance to expand access to clinical trials so that we can move towards life-saving psychedelic therapies for our veterans, service members, and individuals living with PTSD, traumatic brain injury, and substance abuse disorder.”

The FDA published a notice about the new draft guidance on psychedelic research in the Federal Register on June 26. Interested parties now have a 60-day public comment period to provide input on the draft and submit suggestions for the agency to consider before finalizing the guidelines.

Dr. Farchione stated, “By publishing this draft guidance, the FDA aims to outline the challenges associated with designing psychedelic drug development programs and provide information on how to address these challenges. The goal is to help researchers design studies that will yield interpretable results capable of supporting future drug applications.”