Measuring Within-Individual Cannabis Reduction in Clinical Trials: a Review of the Methodological Challenges

PURPOSE: Cannabis abstinence traditionally is the primary outcome in cannabis use disorder (CUD) treatment trials. Due to the changing legality of cannabis, patient goals, and preliminary evidence that suggests individuals who reduce their cannabis use may show functional improvements, cannabis reduction is a desirable alternative outcome in CUD trials. We review challenges in measuring cannabis reduction and the evidence to support various definitions of reduction. FINDINGS: Reduction in number of cannabis use days was associated with improvements in functioning across several studies. Reductions in quantity of cannabis used was inconsistently associated with improvements in functioning, though definitions of quantity varied across studies. Different biomarkers may be used depending on the reduction outcome. CONCLUSIONS: Biologically-confirmed reductions in frequency of cannabis use days may represent a viable endpoint in clinical trials for cannabis use disorder. Additional research is needed to better quantify reduction in cannabis amounts.