Evaluation of Marijuana and Opioid Drug Interactions: Assessment of the Safety Profile, Abuse-Related Pharmacodynamic Effects and Models of Drug Intake

大麻和阿片类药物相互作用的评估：安全性评估、滥用相关药效和药物摄入模型

• 批准号: 10160868
• 负责人: Shanna Babalonis
• 金额: $ 60.93万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160868
• 关键词: Absence of pain sensation; Accidents; Acute; Address; Age; Agonist; Analgesics; Animals; Attenuated; Automobile Driving; Autopsy; Behavior; Behavioral; Biochemical; CNR1 gene; Cannabinoids; Chemosensitization; Cognitive; Data; Dose; Double-Blind Method; Dronabinol; Drug Interactions; Drug Modelings; Enrollment; Epidemic; Evaluation; Funding; Heroin; Human; Illicit Drugs; Individual; Inpatients; Intake; Laws; Legal; Marijuana; Measures; Medical Marijuana; Mus; Opioid; Opioid Receptor; Outcome; Oxycodone; Oxymorphone; Pharmaceutical Preparations; Pharmacodynamics; Physiological; Placebos; Population; Public Health; Randomized; Recording of previous events; Reporting; Research; Risk; Safety; Sampling; Self Administration; Series; Smoke; Specimen; Statutes and Laws; System; THC concentration; Taxes; Therapeutic; Time; Ventilatory Depression; cannabinoid receptor; clinical practice; design; drug discrimination; drug misuse; endogenous cannabinoid system; endogenous opioids; epidemiologic data; functional outcomes; human data; innovation; marijuana use; meetings; mortality; mu opioid receptors; neurochemistry; neurophysiology; nonhuman primate; opioid misuse; opioid mortality; opioid overdose; opioid use; opioid use disorder; opioid user; pain outcome; pain relief; prescription opioid; prescription opioid misuse; receptor; response; safety assessment; safety outcomes; substance use prevention; young adult

Abstract Misuse of prescription opioids and heroin is a global epidemic, with an estimated 33 million people misusing opioids worldwide and 2.6 million individuals in the U.S. meeting criteria for an opioid use disorder. This public health crisis is occurring on the background of a precipitous increase in the availability of marijuana, both in the U.S. and worldwide. Marijuana use is at peak levels in the U.S. – in 2014, 22.2 million individuals 12 years and older reported past month marijuana use and 8.4 million individuals reported daily/near-daily marijuana use. Marijuana and opioids are the two most commonly misused illicit drug classes (with many more taking these drugs therapeutically); however, despite these high rates of use, there are no carefully controlled human data available on their co-use, specifically in regard to drug response, abuse-related measures and safety outcomes. Thus, the current project aims to explore the 1) safety/physiological effects of marijuana and opioid combinations, 2) impact of marijuana use on opioid response and opioid drug-taking, 3) effects of opioid use on marijuana drug-taking, and 4) behavioral and cognitive effects of combined opioid- cannabinoid use. Two independent inpatient studies will be conducted during this 4-year project and each will utilize a randomized, within-subject, double-blind, double-dummy, placebo-controlled design and will enroll samples of non-physically dependent recreational opioid users with histories of marijuana use. Study 1 will examine the effects of smoked marijuana pre-treatment, over a range of THC concentrations (0, 5 &15% THC), on intranasal oxycodone (0, 15 & 30 mg) response, using a full battery of pharmacodynamic outcomes, including safety/physiological response and abuse-related subjective and observer-rated effects. Secondary aims will examine the psychomotor/cognitive effects across the dose conditions. Study 2 will explore 1) the effects of smoked marijuana pre-treatment (0, 15% THC) on intranasal oxycodone (0, 15 & 30 mg) self- administration, and 2) intranasal oxycodone pre-treatment (0, 30 mg) on smoked marijuana (0, 5 & 15% THC) self-administration. Overall, these studies will provide some of the first empirical data on the interaction effects of the two most commonly misused drug classes, providing information on the safety impact, physiological effects and abuse-related effects of their co-use. These findings will be highly relevant to public health considerations, will help determine the risk profile of marijuana and opioid interactions, and will provide new controlled information relevant to clinical practice, prescribing, and public safety.

摘要 滥用处方阿片类药物和海洛因是一种全球流行病，估计有3300万人 滥用阿片类药物在世界各地和260万人在美国符合阿片类药物使用障碍的标准。 这场公共卫生危机是在大麻供应急剧增加的背景下发生的， 无论是在美国还是全世界。在美国，大麻的使用处于高峰水平--2014年，2220万人12 10岁及以上的人报告上个月使用大麻，840万人每天/几乎每天报告 吸食大麻海洛因和阿片类药物是两种最常被滥用的非法药物类别（其中许多 更多地服用这些药物治疗）;然而，尽管使用率很高， 关于其共同使用的受控人体数据，特别是药物反应、滥用相关 措施和安全结果。因此，本项目旨在探索1）安全性/生理效应 大麻和阿片类药物组合，2）大麻使用对阿片类药物反应和阿片类药物服用的影响，3） 阿片类药物使用对大麻吸毒的影响，以及4）联合阿片类药物的行为和认知影响， 大麻素的使用在这个为期4年的项目中，将进行两项独立的住院研究， 采用随机化、受试者内、双盲、双模拟、安慰剂对照设计，并将入组 有大麻使用史的非身体依赖性娱乐性阿片类药物使用者样本。研究1将 检查在THC浓度范围内（0，5和15%THC）吸食大麻预处理的效果， 鼻内羟考酮（0、15和30 mg）反应，使用一整套药效学结果， 包括安全性/生理反应和滥用相关的主观和非主观评定效应。二次 aims将检查不同剂量条件下的心理/认知效应。研究2将探讨1） 熏大麻预处理（0.15%THC）对鼻内羟考酮（0.15&30 mg）自身 给药，和2）鼻内羟考酮预处理（0，30毫克）对吸食大麻（0，5和15%四氢大麻酚） 自我管理。总的来说，这些研究将提供一些关于相互作用效应的第一批经验数据 在两种最常误用的药物类别中，提供了关于安全性影响、生理学影响、 其共同使用的作用和与滥用有关的作用。这些发现将与公共卫生高度相关 考虑，将有助于确定大麻和阿片类药物相互作用的风险状况，并将提供新的 与临床实践、处方和公共安全相关的受控信息。

项目成果

Cannabidiol: pharmacology and therapeutic targets.

• DOI: 10.1007/s00213-020-05712-8
• 发表时间: 2021-01
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Britch SC;Babalonis S;Walsh SL
• 通讯作者: Walsh SL

Cannabinoid Poisoning-Related Emergency Department Visits and Inpatient Hospitalizations in Kentucky, 2017 to 2019.

2017 年至 2019 年肯塔基州与大麻素中毒相关的急诊就诊和住院治疗。

• DOI: 10.1080/10826084.2022.2148478
• 发表时间: 2023
• 期刊: Substance use & misuse
• 影响因子: 2
• 作者: Britch,StevieC;Walsh,SharonL;Vickers-Smith,Rachel;Babalonis,Shanna;Slavova,Svetla
• 通讯作者: Slavova,Svetla

Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim.

• DOI: 10.1186/s42238-022-00140-1
• 发表时间: 2022-06-06
• 期刊: JOURNAL OF CANNABIS RESEARCH
• 影响因子: 3.7
• 作者: Johnson, Erin;Kilgore, Michael;Babalonis, Shanna
• 通讯作者: Babalonis, Shanna