The Food and Drug Administration (FDA) recently issued first-of-its kind draft guidance for investigational new drug (IND) applications involving psychedelic drugs. Citing the rise in interest in exploring the potential therapeutic benefits of psychedelic drugs, FDA indicated its receptiveness to allowing researchers to investigate exactly how useful psychedelics are at treating psychological disorders, such as depression, post-traumatic stress disorder (PTSD), substance abuse, anxiety, and other conditions. While the guidance is not geared toward trials intended to support marketing applications, the agency’s attention to this topic may herald a new wave of associated investigations.

The clinical investigation guidance covers potential trials to explore the medical applications of “classic psychedelic drugs,” such as lysergic acid diethylamide (LSD), psylocibin, and methylenedioxymethamphetamine (MDMA). Because the Drug Enforcement Administration (DEA) still classifies these as Schedule 1 controlled substances, FDA’s proposed guidance places particular emphasis on the need for trial designs that minimize the potential for abuse.

Due to the novelty of this area of research, the draft guidance does not provide specific recommendations on study design, but rather presents “foundational constructs” to be considered. FDA suggests (1) submitting detailed chemical data for the proposed drugs to ensure quality, purity, and strength; (2) following industry best practices for nonclinical trials; (3) exploring a set of specific questions and interactions in any clinical pharmacology testing; (4) closely evaluating potential vectors of abuse; and (5) considering the unique properties of psychedelics when designing clinical trials.

Interest in this field is growing among regulators and the research community. FDA’s draft guidance comes only days after bipartisan congressional lawmakers introduced a bill to direct FDA “to issue guidance on considerations for conducting clinical trials for psychedelic assisted therapy.” The draft guidance also came less than a month after another bipartisan bill proposed a $75 million federal grant program to research how active duty military servicemembers could benefit from psychedelics. The National Institutes of Health and National Institute on Drug Abuse have posted notices of funding opportunities for research projects exploring how psychedelics can treat drug addiction.

A small number of trials involving psychedelics are in advanced stages. The Multidisciplinary Association for Psychedelic Studies (MAPS) is currently overseeing a trial on MDMA-assisted psychotherapy’s potential to treat PTSD, with a goal of receiving final FDA approval as soon as 2024. In November 2022, COMPASS Pathfinder released results from their phase-two trials on psylocibin’s ability to treat depression. These studies could soon be joined by many others, with FDA’s draft guidance pushing psychedelics one step closer to pharmacological legitimacy.

FDA is inviting public comments on its draft guidance until August 25, 2023 (Docket No. FDA-2023-D-1987).