Beyond abstinence: Redefining success in cannabis use disorder treatment

Over two decades of pharmacotherapy research has yet to yield a consistently effective medication for cannabis use disorder (CUD), in part because clinical trials have frequently prioritized abstinence as a primary or key endpoint. Abstinence, however, is difficult for many patients to attain, may not align with their treatment goals, and can obscure meaningful clinical improvements. By contrast, the alcohol and tobacco fields have advanced through adoption of validated reduction-based frameworks that capture changes in harm, functioning, and quality of life.

This paper (1) critiques the limitations of abstinence-focused endpoints in CUD trials, (2) outlines key methodological challenges, and (3) proposes a more comprehensive approach to outcome measurement. Most adult pharmacotherapy trials have been deemed negative when evaluated on abstinence, despite frequent reductions in cannabis use that are associated with improvements in psychiatric symptoms and functional outcomes. Studies evaluating non-abstinent outcomes are often difficult to interpret clinically without clearer links to mental, physical, and functional outcomes. Emerging CUD data and lessons from other substance use fields point to the need for standardized, reduction-based metrics that can more accurately detect treatment-related change.

Reliance on abstinence as the primary endpoint has constrained progress in CUD treatment development. Incorporating consensus-driven, reduction-based outcomes, while continuing to measure abstinence as a secondary endpoint, may better align research with patient goals, enhance interpretability of trial findings, and improve the field's ability to identify promising interventions. Standardizing definitions for meaningful reductions is critical to advancing CUD care.