Cannabidiol in Youth Alcohol Use Disorder

Primary outcomes

1. Concentrations of Glx (i.e., Glutamate + Glutamine)

   Time frame: Changes 3 hours after administration of 600mg CBD vs. placebo

   Using magnetic resonance spectroscopy and a within-subjects design, we measured Concentrations of Glx (i.e., glutamate + glutamine) levels in the anterior cingulate cortex in adolescents during cannabidiol (600mg) or placebo administration. Values provided are absolute values (mmol/kg) measured 3 hours after medication administration. Due to complexities of this method, "normal" levels of Glx are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" glutamate levels when comparing cannabidiol to placebo.

2. GABA+

   Time frame: Changes 3 hours after administration of 600mg CBD vs. placebo

   Using magnetic resonance spectroscopy and a within-subjects design, we measured GABA+ (GABA plus macromolecules) levels in the anterior cingulate cortex in adolescents during cannabidiol (600mg) or placebo administration. Values provided are absolute values (mmol/kg) measured 3 hours after medication administration. Due to complexities of this method, "normal" levels of GABA are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" GABA levels when comparing cannabidiol to placebo.

3. Alcohol Cue Reactivity Neural Activation

   Time frame: Changes 3 hours after administration of 600mg CBD vs. placebo

   Assessing the change in neural reactivity to alcohol cues after each round of medication: Cannabidiol vs. placebo. Cue reactivity is a type of learned response which is observed in individuals who use substances (e.g., alcohol) and involves significant physiological reactions to presentations of substance-related stimuli (i.e., alcohol images) in comparison to neutral images (e.g., non-alcoholic beverages ) measured by BOLD (Blood Oxygen Level-Dependent response). ROIs were (left and right hemisphere): amygdala, caudate, insula, nucleus accumbens, and putamen. The mean Z-statistic within each ROI mask is reported. A Z-score of 0 represents the population mean (e.g., no activation), where higher absolute Z-scores indicate greater evidence of activation (positive or negative) in the ROI compared to baseline. Z-scores do not have inherent clinical thresholds. Higher Z-scores generally reflect stronger task-related BOLD signal changes.

4. Heart Rate Variability

   Time frame: Changes 2 hours after administration of 600mg CBD vs. placebo

   All participants underwent an in vivo, olfactory alcohol cue exposure procedure. Participants smelled water followed by the participant's preferred beverage containing alcohol and apple juice in a counterbalanced order for three minutes each, with a three-minute rest period in between each liquid. The contents were poured into a cup in the participant's presence. During the task, electrocardiogram data were collected and used to create the heart rate variability (HRV) outcome related to the Sympathetic: Vagal ratio, which is the ratio of low-frequency to high-frequency power, derived from spectral HRV analysis. Higher values suggest increased sympathetic activity or reduced vagal activity.

5. PhenX Toolkit Alcohol Urges Questionnaire

   Time frame: Changes 2 hours after administration of 600mg CBD vs. placebo

   All participants underwent an in vivo, olfactory alcohol cue exposure procedure. Participants smelled water followed by the participant's preferred beverage containing alcohol and apple juice in a counterbalanced order for three minutes each, with a three-minute rest period in between each liquid. The contents were poured into a cup in the participant's presence. After each beverage exposure, self-reported alcohol craving was collected via the PhenX Toolkit Alcohol Urges Questionnaire (AUQ). The AUQ consists of eight statements about the participant's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). The participant was asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree" with a scare range of 8 to 56 where higher scores represent higher alcohol craving.