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

项目摘要 随着大麻合法化继续在美国蔓延，平均Δ9-四氢大麻酚（THC） 休闲产品中的THC浓度显著增加，THC水平高达90- 95%。我们 初步数据表明，浓缩使用的大麻血液THC水平是大麻的两倍多 鲜花的使用，以及浓缩使用与更大的戒断，耐受性和大麻使用相关 疾病（CUD），促使人们关注这些高效力产品与问题使用有关的风险 和CUD。此前没有研究评估过有效的治疗方法，以减少这一高危人群的大麻使用。 以前的几项研究发现，非麻醉性大麻素大麻二酚（CBD），可能 拮抗THC对CB 1和CB 2受体的作用，减少大麻使用和CUD相关症状， 例如情感障碍和退缩。这些研究的结果是有希望的，但仅限于合成或 CBD的孤立形式并不广泛。目前还没有大麻衍生的CBD的测试， 大麻衍生的CBD有两种形式，一种是大麻衍生的CBD， 含有少量THC（~0.3% THC，全光谱; fsCBD）和不含THC（0% THC;广谱; bsCBD）。少量的THC可能会在取款方面带来额外的好处， 相关的情感障碍，并反过来有利于减少THC的整体使用。符合本 假设，从我们实验室的试点数据表明，CBD，也含有低水平的THC，减少THC药物 奖励，戒断，焦虑，以及重度浓缩使用者的整体THC使用，支持大麻的潜力- 衍生的CBD，以减少THC的使用，并减轻这一高风险群体的戒断。然而，没有安慰剂对照 已经进行了一项试验，比较了大麻衍生的CBD与THC和无THC对减少THC使用的影响。 该提案的总体目标是进行一项安慰剂对照RCT，比较以下因素的影响： 大麻衍生的CBD（fsCBD vs. bsCBD vs.安慰剂）在减少患有CUD的集中使用者中THC的使用方面。 将招募150名患有DSM 5 CUD的寻求治疗的浓缩液使用者， 议定书参与者将被随机分配服用400 mg大麻衍生的bsCBD（不含 THC）、大麻衍生的fsCBD（含有低水平的THC）或匹配的安慰剂（每组50名参与者） 八个星期。所有参与者都将接受多阶段经验支持的心理干预， 在试验期间支持减少大麻使用。参与者将被评估THC使用的变化[自我- 报告了使用的THC的mg和THC的代谢物11-去甲-9-羧基-Δ9-THC（THC-COOH）]和CUD的水平 症状，以及CBD和CBD的代谢产物，7-羧基大麻二酚（CBD-COOH）的水平，以监测 药物依从性。主要结果包括减少THC暴露[通过自我报告的使用量 和尿THC-COOH（肌酐标准化）]、CUD症状和戒断症状，包括 情感，生理和身体症状方面，在整个8周的研究。

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.