FDA Issues First Ever Guidance for Clinical Trials with Psychedelic Drugs

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The U.S. Food and Drug Administration (FDA) is issuing guidance to provide general considerations to sponsors developing psychedelic drugs for the treatment of medical conditions (e.g., psychiatric disorders, substance use disorders).

Psychedelic is used as shorthand to include classic psychedelics, typically understood to be 5-HT2 agonists such as psilocybin (Magic Mushrooms) and lysergic acid diethylamide (LSD), as well as entactogens or empathogens such as methylenedioxymethamphetamine (MDMA).This is the first FDA draft guidance that presents considerations to the industry for designing clinical trials for psychedelic drugs.

There has been growing interest in the therapeutic potential of psychedelic drugs in recent years. They are being evaluated for use in the potential treatment of conditions such as depression, post-traumatic stress disorder, substance use disorders, and other conditions. However, designing clinical studies to evaluate the safety and effectiveness of these compounds presents a number of unique challenges that require careful consideration.

“Psychedelic drugs show initial promise as potential treatments for mood, anxiety, and substance use disorders. However, these are still investigational products. Sponsors evaluating the therapeutic potential of these drugs should consider their unique characteristics when designing clinical studies,” said Tiffany Farchione, M.D., director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research. “By publishing this draft guidance, the FDA hopes to outline the challenges inherent in designing psychedelic drug development programs and provide information on how to address these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.”

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 (DEA) regulatory requirements.

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 the durability of any treatment effect.

The agency filed the 14-page document two days after a bipartisan coalition in Congress led by Rep. Dan Crenshaw (R-Texas) introduced legislation directing the issuance of clinical trial guidelines.
It also came as 10,000 attendees and hundreds of exhibitors converged on Denver for what was billed as the “largest psychedelic conference in history,” with guests ranging from New York Jets quarterback Aaron Rodgers to National Institute of Mental Health director Joshua Gordon.

“People want to enter the market without having to do the experimentation and the safety and efficacy analysis,” said Kimberly Chew, an attorney at Husch Blackwell focused on psychedelics and emerging therapies. Most don’t want to go through the FDA approval process because it’s expensive, resource intensive, and “they just want their business to thrive,” Chew added.