Considerations in assessing the abuse potential of psychedelics during drug development

The recent increase in clinical research on the potential therapeutic uses of classic psychedelics has prompted the need to revisit the assessment of the abuse potential of these drugs. The term “classic psychedelic” is used in this manuscript to describe serotonergic 5-HT2A agonists that alter perception, cognition, and mood (i.e., psychedelic effects) and that are currently controlled in Schedule I of the Controlled Substances Act (CSA). Schedule I drugs are subject to the most restrictive controls under the CSA, as they are considered to have a high abuse potential and no currently accepted medical use in the United States (USA). However, these classic psychedelics were placed in Schedule I at the time the CSA was enacted in 1970, and their abuse potential has not been systematically assessed using modern methodology. This paper provides an overview of scientific evaluation of the abuse potential of classic psychedelics and delineates the data that will be needed in support of a recommendation for the rescheduling, if a drug product containing a classic psychedelic gains FDA approval. This article is part of the Special Issue on 'National Institutes of Health Psilocybin Research Speaker Series'. •To be approved by FDA, a drug needs to be found safe and effective for its intended use.•In the USA, the Controlled Substances Act (CSA) establishes five schedules of control.•Classic psychedelics are currently controlled in Schedule I of the CSA.•Schedule I drugs have no accepted medical use in the USA.•A new drug application submission for a classic psychedelic will trigger a scientific and medical evaluation to inform rescheduling.