Cannabis Modulation of Outcomes Related to Opioid Use Disorder: Opioid Withdrawal, Opioid Abuse Potential and Opioid Safety

大麻对阿片类药物使用障碍相关结果的调节：阿片类药物戒断、阿片类药物滥用潜力和阿片类药物安全性

• 批准号: 10609065
• 负责人: Shanna Babalonis
• 金额: $ 70.9万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609065
• 关键词: Acute; Address; Affect; Agonist; Anxiety; Benefits and Risks; Buprenorphine; Cannabinoids; Cannabis; Cannabis policy; Clinical Research; Complement; Data; Dose; Double-Blind Method; Dronabinol; Enrollment; FDA approved; Impairment; Individual; Inhalation; Inpatients; Life; Maintenance; Marijuana; Measures; Medical Marijuana; Methadone; Modeling; Naltrexone; Opiate Addiction; Opioid; Oral; Oral Administration; Outcome; Panic; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacodynamics; Physical Dependence; Physiological; Placebo Control; Placebos; Population; Public Advocacies; Public Health; Qualifying; Randomized; Reporting; Research; Research Project Grants; Route; Safety; Sampling; Severities; Statutes and Laws; Study Subject; Tachycardia; Testing; Therapeutic Effect; Time; US State; Ventilatory Depression; Withdrawal; abuse liability; cannabis administration; cannabis withdrawal; clinical practice; design; drug misuse; effective therapy; epidemiology study; high risk population; illicit drug use; innovation; marijuana use; medication for opioid use disorder; mortality; opioid abuse; opioid epidemic; opioid misuse; opioid mortality; opioid overdose; opioid use; opioid use disorder; opioid withdrawal; overdose death; placebo group; respiratory; sleep quality

Abstract Opioids and cannabinoids are the two most widely used and misused drug classes. Worldwide, an estimated 53 million people misuse opioids. In the US, 2.6 million individuals meet criteria for opioid use disorder and nearly 47,000 people died in 2019 due to opioid overdose. At the same time, global cannabis (i.e., marijuana) use is also at record high levels - in 2018, 43.5 million individuals in the US reported past-year cannabis use. Despite high rates of both licit and illicit use of these drug classes, there are no controlled data on the effects of cannabis in one of the most high-risk groups – individuals with opioid use disorder. Thus, the current project aims to explore how both acute (Study 1) and repeated (Study 2) cannabis administration impacts 1) opioid abuse potential, 2) opioid withdrawal severity, and 3) opioid safety/physiological effects. Two independent inpatient studies will be conducted during this 4-year project and each will utilize a randomized, within-subject, double-blind, placebo-controlled design and will enroll samples of participants with moderate to severe opioid use disorder (with current physical dependence) and limited past-month cannabis use. Study 1 will examine the effects of 7 acute cannabis doses, including a 6-fold dose range of THC (5, 10, 20, 30 mg), THC/CBD doses across a 3-fold dose range (10:10 mg; 30:30 mg THC:CBD) and matched placebo on outcomes related to 1) opioid abuse liability (i.e., ratings of high, drug liking) during an acute opioid challenge, 2) withdrawal severity (during acute instances of opioid withdrawal), and 3) safety/physiological effects (e.g., respiratory drive) of the drug conditions and combinations. Study 2 will explore the effects of repeated inhaled cannabis (3 times/day for 6.5 consecutive days), across three randomized dosing blocks (two active cannabis doses, matched placebo), to determine how a repeated cannabis dosing model impacts outcomes related to 1) opioid abuse potential (i.e., ratings of high, drug liking) assessed during an acute opioid challenge; 2) withdrawal severity (measured during acute instances of opioid withdrawal), 3) safety/physiological effects (e.g., respiratory drive) of the drug conditions and combinations; and 4) cannabis tolerance and withdrawal. Cannabis modulation of sleep quality during bouts of acute opioid withdrawal will also be explored. Both studies will employ a full complement of pharmacodynamic outcomes, including subjective and observer-rated measures, as well as a full battery of physiological and psychomotor outcomes related to safety and impairment to fully assess the potential risk/benefit profile of cannabis in OUD. Overall, these timely and innovative studies will provide the first empirical data on the effects of inhaled cannabis in an opioid-dependent population. These studies will provide new controlled information on potential interactions relevant to clinical practice, prescribing, and public safety.

抽象的 阿片类药物和大麻素是世界范围内使用最广泛和滥用的两种药物。 据估计，有 5300 万人滥用阿片类药物。在美国，有 260 万人符合阿片类药物使用标准。 2019 年，全球有近 47,000 人因阿片类药物过量死亡。 （即大麻）使用量也创下历史新高——2018 年，美国有 4,350 万人报告去年吸食大麻的人数 尽管这些药物类别的合法和非法使用率很高，但没有受控数据。 大麻对最高风险群体之一——阿片类药物使用障碍患者的影响。 当前项目旨在探索急性（研究 1）和重复（研究 2）大麻管理如何 影响 1) 阿片类药物滥用的可能性，2) 阿片类药物戒断的严重程度，以及 3) 阿片类药物的安全性/生理影响 两个。 在这个为期 4 年的项目中将进行独立的住院患者研究，每项研究都将利用随机、 受试者内、双盲、安慰剂对照设计，并将招募患有中度至 严重的阿片类药物使用障碍（目前存在身体依赖性）和过去一个月有限的大麻使用研究 1。 将检查 7 种急性大麻剂量的影响，包括 6 倍剂量范围的 THC（5、10、20、30 毫克）， THC/CBD 剂量跨 3 倍剂量范围（10:10 mg；30:30 mg THC:CBD）和匹配的安慰剂 与 1) 在急性阿片类药物挑战期间阿片类药物滥用倾向（即高评级、药物喜好）相关的结果， 2) 戒断严重程度（在阿片类药物戒断的急性情况下），以及 3) 安全/生理影响（例如， 研究 2 将探讨反复吸入的影响 大麻（每天 3 次，连续 6.5 天），跨越三个随机剂量组（两种活性大麻 剂量，匹配的安慰剂），以确定重复的大麻剂量模型如何影响与 1）相关的结果 在急性阿片类药物挑战期间评估阿片类药物滥用可能性（即高、药物喜好评级）；2) 戒断严重程度（在阿片类药物戒断的急性情况下测量），3) 安全/生理影响 （例如，呼吸驱动）药物状况和组合；以及 4) 大麻耐受和戒断。 还将探讨大麻在急性阿片类药物戒断期间对睡眠质量的调节。 研究将采用完整的药效学结果，包括主观和观察者评价 措施，以及与安全和相关的全套生理和精神运动结果 总体而言，这些及时而有效地评估了大麻在 OUD 中的潜在风险/效益状况。 创新研究将提供第一个关于吸入大麻对阿片类药物依赖者影响的经验数据 这些研究将提供与临床相关的潜在相互作用的新的受控信息。 实践、处方和公共安全。