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.

项目摘要 随着大麻合法化继续遍及美国，平均Δ9-四氢大麻酚（THC） 休闲产品的浓度显着升高，THC水平高达90-95％。我们的 初步数据表明，浓缩物使用引起的血液THC水平高于大麻的两倍以上 花朵使用，而浓缩物的使用与更大的戒断，耐受性和大麻使用有关 疾病（CUD），引起人们对这些高效力产品与问题使用的风险的关注 和cud。没有先前的研究评估了有效的治疗方法，以减少这个高风险组中的大麻使用。 先前的几项研究发现，无毒性大麻素大麻二酚（CBD）可能 拮抗THC对CB1和CB2受体的影响，减少大麻的使用和与CUD相关的符号， 例如情感灾难和戒断。承诺这些研究的结果，但仅限于合成或 孤立的CBD形式，这些形式不广泛。没有对大麻衍生的CBD的测试 大麻衍生的CBD在美国各地无处方的情况下可用，有两种形式，一种 少量THC（〜0.3％THC，全光谱； FSCBD）和一个没有THC（0％THC; Broad Spectrum; BSCBD）。少数THC可能会在撤离方面付出额外的收益和 相关受影响的疾病，进而有益于减少THC总体使用。与此一致 假设我们实验室的试点数据表明，CBD也含有低水平的THC，可降低THC药物 奖励，戒断，焦虑和整体THC在重点浓缩使用者中使用，支持大麻的潜力 派生的CBD可减少THC使用并减轻此高风险组的撤离。但是，没有安慰剂控制 试验已进行了比较，在减少THC使用方面，与大麻衍生的CBD进行了比较。 该提案的总体目标是进行安慰剂对照的RCT，以比较 大麻衍生的CBD（FSCBD vs. BSCBD与安慰剂）在减少CUD的浓缩物用户中使用THC。 将招募150种成人治疗DSM5 CUD的浓缩用户以完成为期八周 协议。参与者将被随机分配为400毫克大麻衍生的BSCBD（包含否 THC），大麻衍生的FSCBD（包含低水平的THC）或匹配的安慰剂（每组50名参与者） 八周。所有参与者都将获得多课的经验支持的心理干预措施 支持大麻在试验期间使用减少。将评估参与者使用THC的变化[自我 报道了使用的THC的毫克和THC代谢物11-NOR-9-Carboxy-Δ9-THC（THC-COOH）和CUD的水平 症状以及CBD和CBD的代谢物，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[通过使用的自我报告的数量 和尿液thc-cooh（肌酐标准化）]，cud符号和提取符号，包括 在整个8周的研究中，情感，身体和身体症状方面。