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

大麻衍生的大麻二酚用于治疗浓缩使用者的大麻使用障碍：一项双盲安慰剂对照随机试验

• 批准号: 10825337
• 负责人: L. Cinnamon Bidwell
• 金额: $ 74.19万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10825337
• 关键词: Abstinence; Acute; Adult; Affective; Anxiety; Blood; CNR1 gene; CNR2 gene; Cannabidiol; Cannabinoids; Cannabis; Creatinine; DSM-V; Data; Double-Blind Method; Flowers; Goals; Hemp; Intervention; Intoxication; Laboratories; Marketing; Measures; Mediating; Methods; Monitor; Participant; Patient Self-Report; Pharmaceutical Preparations; Physiological; Placebo Control; Placebos; Preparation; Protocols documentation; Public Health; Randomized; Randomized, Controlled Trials; Recreation; Research; Standardization; Symptoms; THC concentration; THC exposure; Testing; Tetrahydrocannabinol; United States; Urine; Withdrawal; Withdrawal Symptom; affective disturbance; cannabis seeking; drug reward; effective therapy; high risk; high risk population; marijuana legalization; marijuana use; marijuana use disorder; marijuana user; medication compliance; negative affect; physical symptom; placebo controlled trial; primary outcome; psychologic; randomized placebo controlled trial; recruit; telehealth; trial comparing; week trial

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.

项目概要 随着大麻合法化继续在美国蔓延，平均 Δ9-四氢大麻酚 (THC) 娱乐产品中的 THC 浓度显着增加，我们的 THC 含量高达 90-95%。 初步数据表明，浓缩使用引起的血液 THC 水平是大麻的两倍多 花的使用，以及浓缩物的使用与更大的戒断、耐受性和大麻使用有关 紊乱（CUD），引发人们对这些高效产品与问题使用相关的风险的担忧 之前没有研究评估减少这一高危人群使用大麻的有效治疗方法。 之前的几项研究发现，非醉人的大麻素大麻二酚（CBD）可能 拮抗 THC 对 CB1 和 CB2 受体的影响，减少大麻使用和 CUD 相关症状， 这些研究的结果是有希望的，但仅限于合成或戒断。 尚未广泛使用的 CBD 的分离形式尚未对大麻衍生的 CBD 进行过测试。 在美国无需处方即可广泛使用。重要的是，大麻衍生的 CBD 有两种形式，一种是 含有少量 THC（~0.3% THC，全谱；fsCBD），一种不含 THC（0% THC；广谱；fsCBD） bsCBD）。少量的 THC 可能会在戒断和治疗方面带来额外的好处。 相关的情感障碍，进而有利于减少 THC 的整体使用。 假设，我们实验室的试点数据表明 CBD 也含有低水平的 THC，可以减少 THC 药物 奖励、戒断、焦虑和重度浓缩使用者的 THC 总体使用情况，支持了大麻的潜力 衍生的 CBD 可以减少 THC 使用并减轻这一高风险人群的戒断症状，​​但没有安慰剂对照。 已经进行了一项试验，比较含有和不含有 THC 的大麻衍生 CBD 在减少 THC 使用方面的作用。 该提案的总体目标是进行安慰剂对照随机对照试验，比较以下药物的效果： 大麻衍生的 CBD（fsCBD 与 bsCBD 与安慰剂）减少患有 CUD 的集中使用者的 THC 使用。 将招募 150 名寻求 DSM5 CUD 集中治疗的成年用户来完成为期八周的研究 参与者将被随机分配服用 400 毫克大麻衍生的 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）每天 所有参与者将接受为期八周的多次经验支持的心理干预。 支持试验期间减少大麻使用。将对参与者进行 THC 使用变化的评估[自我评估]。 报告使用的 THC 毫克数以及 THC 代谢物 11-nor-9-carboxy-Δ9-THC (THC-COOH)] 和 CUD 的水平 症状，以及 CBD 和 CBD 代谢物 7-羧基大麻二酚 (CBD-COOH) 的水平进行监测 主要结果包括减少 THC 暴露[通过自我报告的使用量] 和尿液 THC-COOH（肌酐标准化）]、CUD 症状和戒断症状，​​包括 在为期 8 周的研究中，人们所面临的情感、生理和身体症状。