Hemp-derived Cannabidiol for the treatment of cannabis use disorder in concentrate users: A double-blind placebo-controlled randomized trial

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Project Summary As cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol (THC) concentrations in recreational products have significantly increased, with THC levels as high as 90-95%. Our preliminary data suggest that concentrate use elicits blood THC levels more than twice as high as cannabis flower use, and that concentrate use is associated with greater withdrawal, tolerance, and Cannabis Use Disorder (CUD), prompting concern about the risks of these high potency products in relation to problem use and CUD. No prior study has evaluated effective treatments to reduce cannabis use in this high risk group. Several previous studies have found that the non-intoxicating cannabinoid cannabidiol (CBD), which may antagonize the effects of THC on CB1 and CB2 receptors, reduces cannabis use and CUD-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising, but limited to synthetic or isolated forms of CBD that are not widely available. There have been no tests of the hemp-derived CBD that is widely available without a prescription across the U.S. Importantly, hemp-derived CBD comes in two forms, one with a small amount of THC (~0.3% THC, full spectrum; fsCBD) and one without THC (0% THC; broad spectrum; bsCBD). It is possible that a small amount of THC may confer additional benefits with respect to withdrawal and related affective disturbance, and in turn be beneficial for reducing THC use overall. Consistent with this hypothesis, pilot data from our lab suggest that CBD, that also contains low levels of THC, reduces THC drug reward, withdrawal, anxiety, and overall THC use in heavy concentrate users, supporting the potential for hemp- derived CBD to reduce THC use and mitigate withdrawal in this high risk group. However, no placebo-controlled trial has been conducted comparing hemp-derived CBD with and without THC on reducing THC use. The overarching goal of this proposal is to conduct a placebo-controlled RCT comparing the effects of hemp-derived CBD (fsCBD vs. bsCBD vs. placebo) on reducing THC use in concentrate users with CUD. 150 adult treatment seeking concentrate users with DSM5 CUD will be recruited to complete an eight-week protocol. Participants will be randomly assigned to take 400 mg of either hemp-derived bsCBD (contains no THC), hemp-derived fsCBD (contains low levels of THC), or matched placebo (50 participants per group) daily for eight weeks. All participants will receive a multi-session empirically supported psychological intervention to support cannabis use reduction during the trial. Participants will be assessed for changes in THC use [self- reported mg of THC used and levels of THC’s metabolite 11-nor-9-carboxy-Δ9-THC (THC-COOH)] and CUD symptoms, as well as levels of CBD and CBD’s metabolite, 7-Carboxy-Cannabidiol (CBD-COOH) to monitor medication adherence. Primary outcomes include reduction in THC exposure [via self-reported amount used and urine THC-COOH (standardized for creatinine)], CUD symptoms, and withdrawal symptoms, including affective, physiological, and physical symptom facets, across the 8 week study.