Subjective drug-effect ratings predict cannabis self-administration in people who use cannabis daily

As interest in the potential therapeutic benefits of cannabis-derived products grows, accurate predictors of abuse potential will be vital for informing regulatory decisions. Currently, the Food and Drug Administration recommends using subjective effect ratings of Drug Liking as the primary measure in human abuse potential studies. However, dissociations between subjective ratings and drug-taking behavior have been previously reported. This retrospective analysis determined if any subjective effects questionnaire items uniquely predicted cannabis self-administration in people who use cannabis daily (N = 89; 71 male and 18 female). Data from 4 previous studies across 2 research sites that included cannabis self-administration and subjective effects assessments were combined. Concentrations of Δ⁹-tetrahyrdocannabinol (THC) were similar across studies (5.5%, 5.6%, or 5.9%), although milligram THC dose varied based on administration procedures. Ratings of Good Effect, High, Sedated/Tired, Drug Liking, Stimulated, and Willingness to Take Again were used as predictors. In each study, a money option ($0.50 or $1.00) was scheduled as an alternative to cannabis puffs in self-administration procedures. Proportion of choices for cannabis puffs over total choice trials (3 or 8 trials) was used as the primary outcome. Generalized linear models revealed that higher ratings of Willingness to Take Again (OR = 1.04) were associated with increased odds of self-administering active THC cannabis, while higher ratings of Stimulated were associated with decreased odds of self-administering placebo cannabis (OR = 0.94). These results suggest that subjective ratings of Willingness to Take Again should be considered as a primary outcome when assessing abuse potential for novel cannabinoid products. SIGNIFICANCE STATEMENT: This retrospective analysis found that subjective ratings of Willingness to Take Again was a more predictive measure of cannabis self-administration than Drug Liking in people who use cannabis daily. Refining human abuse potential assessments to prioritize measures that better align with drug-taking behavior could improve regulatory evaluations of novel cannabinoid products.