Cannabis Craving and Cross-Substance Substitution During Cannabis Treatment: Initial Insights Across Seven Cannabis Use Disorder Clinical Trials

BACKGROUND:Cannabis cessation or reduction may increase cross-substance substitution in response to craving or reduced use. Evidence for substitution is mixed, and treatment effects remain unclear. This exploratory study examined alcohol and tobacco substitution within clinical trials of cannabis cessation. DESIGN:Data were pooled from 829 participants (Mage = 27.1, SD = 9.1; 31 % female; 63 % White; 13 % Latine/Hispanic) across seven pharmacologic cannabis use disorder (CUD) trials. Weekly cannabis, alcohol, and cigarette use were assessed (cigarettes in six trials). Longitudinal mixed-effects models tested whether cannabis use or craving predicted next-week alcohol and cigarette outcomes, with treatment condition included as a moderator. RESULTS:No significant three-way interactions with treatment emerged. Cannabis craving interacted with cannabis frequency to predict modest increases in next-week alcohol quantity (b = 0.009, p = 0.04970497), although not drinking frequency. Higher cannabis quantity predicted lower next-week cigarette quantity (b =  - 0.009, p = 0.042). There was limited evidence of a treatment × craving interaction for cigarette frequency (b =  - 0.008, p = 0.04990499), with higher craving associated with fewer smoking days in the active treatment arm. CONCLUSIONS:Alcohol findings were consistent with complementary use patterns, whereas cigarette smoking showed evidence of both concurrent coco-use and prospective substitution with cannabis. Pharmacotherapy did not broadly alter these relationships; however, among participants receiving active treatment, greater cannabis craving was associated with fewer smoking days. These findings provide initial evidence supporting monitoring of polysubstance use during CUD treatment and consideration of how cessation efforts may differentially affect alcohol and tobacco use.