Per the United States Food and Drug Administration (FDA’s) 2017 abuse potential guidance document, all drugs with central nervous system (CNS) activity under development should be evaluated for abuse potential. A full abuse potential assessment (APA) includes identifying potential abuse-related adverse events (ARAEs) in all clinical safety and efficacy studies. S1-221 is a combination cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) product being developed for the acute treatment of migraine.
A Phase 1 single ascending dose (SAD) study (DLP-S-0-1.01) was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of different doses and ratios of orally administered S1-221 in healthy participants. A total of 8 cohorts consisting of 8 participants each (randomized 6:2, active:placebo) has been completed and data analysis is ongoing. The study evaluated ratios of CBD:THC ranging from 25:1 to 300:1 and doses ranging from 250 to 1000 mg CBD and 2.5 to 10 mg THC. As part of the overall APA strategy for S1-221, potential ARAEs were prospectively evaluated as AEs of special interests (AESIs) using a prespecified list of adverse event (AE) terms recommended by FDA.)
The objectives of this presentation are to: (1) Provide background information about the importance of collecting ARAE data as part of an overall APA of a drug in development, and (2) Summarize the methods used to monitor for AESIs in study DLP-S-0-1.01 and present results of the evaluation in the form of AESI narratives.
Authors: Ryan K. Lanier, Sarah Thayer, Joe Seroogy, Terrance Ocheltree, Alan M. Rapoport, George Pappas
This study was funded by Delphian Therapeutics.
Presented at The College on Problems of Drug Dependence 88th Annual Scientific Meeting, June 2026.Lanier_CPDD_2026_Poster_FINAL_09Jun2026
