FDA Issues First Draft Guidance on Clinical Trials With Psychedelic Drugs

WASHINGTON — The Food and Drug Administration on Friday published a new draft guidance on what researchers should consider when investigating the use of psychedelic drugs for potential treatment of medical conditions, including psychiatric or substance use disorders. 

The first-of-its-kind guidance comes amid growing interest in the therapeutic potential of psychedelic drugs, particularly when it comes to treating conditions like depression, post-traumatic stress disorder and substance use disorders.

But as the agency acknowledged in releasing the new guidelines, designing clinical studies to evaluate the safety and effectiveness of these compounds presents a number of unique challenges.

“Psychedelic drugs show initial promise as potential treatments for mood, anxiety and substance use disorders. However, these are still investigational products,” said Dr. Tiffany Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, in a written statement.

“Sponsors evaluating the therapeutic potential of these drugs should consider their unique characteristics when designing clinical studies,” Farchione continued. “By publishing this draft guidance, the FDA hopes to outline the challenges inherent in designing psychedelic drug development programs and provide information on how to address these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 that will be capable of supporting future drug applications,” she said.

The draft guidance offers direction to researchers on study design and other considerations as they develop medications that contain psychedelics. 

Within the draft guidance, the term psychedelics refers to “classic psychedelics,” typically understood to be drugs such as psilocybin and lysergic acid diethylamide that act on the brain’s serotonin system, as well as “entactogens” or “empathogens” such as methylenedioxymethamphetamine.

The document describes basic considerations throughout the drug development process including trial conduct, data collection, subject safety and new drug application requirements. For example, psychedelic drugs may produce psychoactive effects such as mood and cognitive changes, as well as hallucinations. 

As a result, there is the potential for abuse of these drugs, which is a drug safety issue that requires careful consideration and putting sufficient safety measures in place for preventing misuse throughout clinical development. 

For psychedelics that are currently Schedule I controlled substances, the draft guidance notes that activities associated with investigations under an Investigational New Drug Application must comply with applicable Drug Enforcement Administration regulatory requirements.

The evidentiary standard for establishing 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 the durability of any treatment effect. 

The FDA is encouraging the public to provide comments on the draft guidance. Comments should be submitted within 60 days to ensure the agency considers them. 

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