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.

摘要