Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder.

Abstinence is rarely achieved in clinical trials for cannabis use disorder (CUD). Cannabis reduction is associated with functional improvement, but reduction endpoints have not been established, indicating a need to identify and validate clinically meaningful reduction endpoints for assessing treatment efficacy.

In this study, data from a 12-week double-blind randomized placebo-controlled medication trial for cannabis cessation (CTN-0053, ACCENT) were analyzed. Participants (N = 225) were treatment-seeking adults, M = 30.6 (8.9) years old, 70.2% male, and 42.2% non-white, with CUD who completed 12 weeks of treatment. Frequency (days of use per week) and quantity (grams per using day) were used to define high-, medium-, and low-risk levels. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and cannabis-related problems were assessed using the Marijuana Problems Scale. General linear models for repeated measures tested associations between the magnitude of risk reduction and functional outcomes from baseline (BL) to end-of-treatment (EOT).

Results found that cannabis risk levels were sensitive to reductions in use from BL to EOT for frequency- and quantity-based metrics. Magnitude reduction in frequency-based risk level was associated with magnitude decrease in depression, anxiety, and cannabis-related problems. Magnitude reduction in quantity-based risk level was associated with magnitude decrease in anxiety and cannabis-related problems.

Conclusions: Cannabis use risk levels, as operationalized in this study, captured reductions in use during a clinical trial. Risk level reduction was associated with functional improvement suggesting that identifying risk levels and measuring the change in levels over time may be a viable and clinically meaningful endpoint for determining treatment efficacy.

Related protocols: CTN-0053