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两种最广泛使用和未经遗忘的药物类别。全球，一个 估计有5300万人滥用Ooids。在美国，有260万个人符合OOID使用的标准 由于阿片类药物过量，2019年疾病和近47,000人死亡。同时，全球大麻 （即大麻）使用也处于创纪录的高水平 - 2018年，美国有4,350万人报告了过去的一年 大麻使用。尽管具有高度使用这些药物类别的持有率和非法使用率，但没有受控数据 关于大麻在最高风险群体之一的影响 - 患有阿片类药物使用障碍的个体。那， 当前的项目旨在探讨急性（研究1）和重复（研究2）大麻给药 影响1）阿片类药物滥用潜力，2）阿片类药物戒断严重程度，3）阿片类药物安全/生理影响。二 在这个4年的项目中将进行独立的住院研究，每个研究都将使用随机的， 受试者内，双盲，安慰剂对照设计，并将注册中等的参与者样本 严重的阿片类药物使用障碍（当前的身体依赖性）和过去月份的大麻使用有限。研究1 将检查7种急性大麻剂量的影响，包括6倍的THC（5、10、20、30 mg）， THC/CBD剂量的3倍剂量范围（10:10 mg; 30:30 mg THC：CBD）并与安慰剂匹配 与1）急性阿片类药物挑战期间的阿片类药物滥用责任（即，高毒品的评级）有关的结果， 2）戒断严重程度（在阿片类药物戒断的急性实例中）和3）安全/生理效应（例如， 药物条件和组合的呼吸驱动。研究2将探索重复继承的效果 大麻（连续3.5天/天3次），跨三个随机剂量块（两个活性大麻 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） 在急性绿opire挑战期间评估了卵毒素滥用潜力（即，高分，药物喜欢的评分）； 2） 提取严重程度（在阿片类药物戒断的急性实例中测量），3）安全/生理效应 （例如，呼吸驱动）药物条件和组合； 4）大麻耐受性和戒断。 还将探讨急性阿片类药物戒断期间睡眠质量的大麻调节。两个都 研究将采用完全补充药物代谢结果，包括主观和观察者等级 措施，以及与安全性以及 充分评估OUD大麻的潜在风险/收益概况的损害。总体而言，这些及时 创新研究将提供有关阿片类药物依赖性大麻的影响的第一个经验数据 人口。这些研究将提供有关与临床相关的潜在相互作用的新的受控信息 练习，开处方和公共安全。