Impact of vaporized cannabis with varying cannabidiol and THC ratios on opioid abuse-liability and analgesia

不同大麻二酚和 THC 比例的汽化大麻对阿片类药物滥用责任和镇痛的影响

• 批准号: 9750248
• 负责人: Caroline A Arout
• 金额: $ 20.25万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750248
• 关键词: Absence of pain sensation; Address; Adverse effects; Affect; Analgesics; Cannabidiol; Cannabinoids; Cannabis; Cannabis Abuse; Centers for Disease Control and Prevention (U.S.); Cessation of life; Controlled Study; Data; Data Reporting; Disease; Dose; Double-Blind Method; Drug Combinations; Effectiveness; Epidemiology; Human; Inhalation; Internet; Knowledge; Laboratories; Laboratory Study; Legal; Measures; Medical; Medical Marijuana; Opioid; Opioid Analgesics; Outpatients; Oxycodone; Pain; Participant; Patient Self-Report; Patients; Physicians; Placebos; Policies; Public Health; Reporting; Risk; Route; Sativex; Self Administration; Sex Differences; Smoke; THC concentration; Techniques; Testing; Tetrahydrocannabinol; Therapeutic; Therapeutic Uses; Time; Vaporizer; Woman; chronic neuropathic pain; chronic pain; design; experience; marijuana use; marijuana user; men; opioid abuse; opioid epidemic; opioid policy; opioid use; pain patient; pre-clinical; prescription opioid; prescription opioid abuse; public health priorities; recruit; response; vapor; vaporization; volcano

Project Summary: An estimated 60% of medical cannabis patients report concomitant use of prescription opioids to alleviate pain, yet there is an enormous gap in our understanding of how the drug combination impacts opioid abuse liability and analgesic effectiveness. Studies in our laboratory have demonstrated that cannabis (1) produces dose-related increases in analgesia measured with the Cold Pressor Test (CPT), a reliable and validated pain induction technique that has predictive validity for analgesics that are used for chronic pain, and (2) enhances the analgesic effects of a sub-threshold analgesic dose of the popularly prescribed opioid, oxycodone (OXY; 2.5 mg) without increasing cannabis’s abuse liability. However, these studies did not directly assess the impact of the combination on oxycodone’s abuse liability, a critical public health concern given the rising rates of prescription opioid abuse. Furthermore, the cannabis used previously had negligible concentrations of cannabidiol (CBD), a non-intoxicating cannabinoid that is hypothesized to decrease the abuse liability of tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, and opioids. CBD is also hypothesized to alleviate chronic (neuropathic) pain. Despite the widespread medical use and availability of cannabis with varying THC:CBD ratios, no studies have assessed how cannabis with varying ratios of THC:CBD affects cannabis’s abuse liability or analgesia when administered alone, or opioid abuse liability and analgesia when given in combination. The proposed study would be the first examination of the abuse liability and analgesic effectiveness of vaporized cannabis with high (~30:1) equal (~1:1) and low (~1:30) THC:CBD ratios, a route of administration and THC:CBD ratios that are ecologically relevant. Healthy cannabis users (N=20, 10M, 10F) with limited opioid experience will complete 8 outpatient laboratory sessions, during which they will be administered a sub- threshold analgesic dose of OXY (2.5 mg) or placebo, followed by inhalations of 30:1, 1:1, 1:30 THC:CBD, or placebo cannabis vapor via Volcano® vaporizers. The 30:1 dose will match the 1:1 dose on total THC content, but contain < 1 mg of CBD; the 1:30 dose will match the 1:1 dose on total CBD content, but contain < 1 mg THC. This design allows us to examine the independent and combined effects of THC and CBD on measures of abuse liability (positive subjective effects, self-administration) and analgesia when administered alone and when combined with OXY. Reducing the therapeutic dose and abuse liability of RxOPs while effectively treating pain is a public health priority. Cannabinoids hold promise, but there is an alarming absence of scientific data to inform if they mitigate or enhance adverse effects. The proposed study would provide urgently needed data on the effects of THC and CBD on abuse liability, therapeutic utility of medical cannabis and cannabinoids for chronic pain, and their effects when combined with RxOPs.

项目摘要：估计 60% 的医用大麻患者报告同时使用处方药 阿片类药物可以减轻疼痛，但我们对药物组合如何发挥作用的理解存在巨大差距 我们实验室的研究表明，影响阿片类药物滥用的可能性和镇痛效果。 大麻 (1) 产生与剂量相关的镇痛增加，通过冷加压试验 (CPT) 进行测量，冷压试验 (CPT) 是一种 可靠且经过验证的疼痛诱导技术，对用于镇痛的药物具有预测有效性 慢性疼痛，(2) 增强普遍使用的亚阈值镇痛剂量的镇痛效果 处方阿片类药物羟考酮（OXY；2.5 毫克）不会增加大麻的滥用可能性然而，这些。 研究没有直接评估该组合对羟考酮滥用倾向的影响，这是一个批评公众 鉴于处方阿片类药物滥用率不断上升，健康问题进一步加剧。 大麻二酚 (CBD) 的浓度可以忽略不计，这是一种无毒的大麻素，被破坏后 减少四氢大麻酚（THC）的滥用可能性，THC是大麻的主要精神活性成分， 尽管医学上广泛使用，但 CBD 也有助于缓解慢性（神经性）疼痛。 大麻的使用和可用性具有不同的 THC:CBD 比例，没有研究评估大麻如何 THC:CBD 的不同比例会影响大麻或阿片类药物单独给药时的滥用倾向或镇痛作用 组合使用时的滥用倾向和镇痛。 拟议的研究将是对滥用倾向和镇痛效果的首次检查 具有高（~30:1）相等（~1:1）和低（~1:30）THC:CBD比率的汽化大麻，一种给药途径 与生态相关的 THC:CBD 比率（N=20、10M、10F）有限。 阿片类药物经验将完成 8 个门诊实验室课程，在此期间他们将接受亚 OXY（2.5 毫克）或安慰剂的镇痛阈值剂量，然后吸入 30:1、1:1、1:30 THC:CBD，或 通过 Volcano® 蒸发器的大麻蒸气 30:1 剂量将与总 THC 含量的 1:1 剂量相匹配， 但含有 < 1 毫克 CBD；1:30 剂量将与 1:1 剂量的 CBD 总含量相匹配，但含有 < 1 毫克 THC。这种设计使我们能够检查 THC 和 CBD 对措施的独立和综合影响。 单独给药时的滥用倾向（积极的主观效果、自我给药）和镇痛 与 OXY 联合使用时，可有效降低 RxOP 的治疗剂量和滥用可能性。 治疗疼痛是一项公共卫生优先事项，大麻素有望实现这一目标，但令人震惊的是，大麻素的缺乏。 拟议的研究将紧急提供科学数据，以告知它们是否减轻或增强了不利影响。 需要有关 THC 和 CBD 对滥用倾向、医用大麻的治疗效用的影响的数据 大麻素治疗慢性疼痛及其与 RxOP 联合使用的效果。

项目成果

Necessity of addressing motivations for cannabis use to guide research.

有必要解决大麻使用的动机以指导研究。

• 发表时间: 2019
• 作者: Cooper, Ziva D;Adinoff, Bryon
• 通讯作者: Adinoff, Bryon