The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial

Novel treatment evaluation for youth with alcohol use disorder (AUD) is needed. Cannabidiol (CBD), a constituent of the Cannabis sativa plant, may be a promising candidate pharmacotherapy due to its potential therapeutic properties and preclinical research suggesting it decreases alcohol use. Due to limited data in humans, rigorous screening of the acute neural, psychophysiological, and alcohol-related effects of CBD is indicated to assess its viability as a potential treatment for youth AUD. Using a within-subjects, randomized, double-blind, placebo-controlled design, we tested acute multi-modal effects of CBD (600 mg) in non-treatment seeking youth with AUD (N = 36; ages 17-22; 69% female). Outcomes included (1) glutamate+glutamine (Glx) and GABA levels in the anterior cingulate cortex measured with proton magnetic resonance spectroscopy; (2) whole-brain and a priori region-of-interest neural alcohol cue-reactivity measured with functional MRI; (3) psychophysiological response to alcohol olfactory cues measured by self-reported acute alcohol craving, heart rate variability, and skin conductance; and (4) alcohol use. No CBD-associated adverse events were observed. There were no effects of acute CBD administration, compared to placebo, on any outcomes of interest. This is the first adequately powered medication screening study for the use of CBD in youth with AUD. We did not detect significant effects of CBD on neurometabolic, neurobehavioral, psychophysiological, or alcohol use outcomes in this sample. Future studies may benefit from chronic administration to better understand substance-related effects.