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

项目摘要：估计60%的医用大麻患者报告同时使用处方 阿片类药物用于缓解疼痛，但我们对药物组合的理解存在巨大差距 影响阿片类药物滥用倾向和止痛效果。我们实验室的研究表明， 通过冷加压试验(CPT)测量，大麻(1)产生与剂量相关的镇痛增加，a 可靠和有效的疼痛诱导技术，对用于以下疾病的止痛药具有预测有效性 慢性疼痛，以及(2)增强一般阈值下止痛剂的止痛效果 处方类阿片，羟考酮(羟考酮；2.5毫克)，不增加大麻的滥用风险。然而，这些 研究没有直接评估联合使用对羟考酮滥用责任的影响，羟考酮是一种关键的公众 鉴于处方阿片类药物滥用的比率不断上升，人们对健康感到担忧。此外，之前使用过的大麻 大麻二酚(CBD)的浓度可以忽略不计，这是一种非醉人的大麻类化合物，假设 减少大麻的主要精神活性成分四氢大麻酚(THC)的滥用可能性， 和阿片类药物。CBD也被认为可以缓解慢性(神经性)疼痛。尽管广泛存在的医疗保健 大麻的使用和可获得性具有不同的THC：CBD比率，没有研究评估大麻与 不同比例的THC：CBD影响大麻的滥用倾向或单独给药或阿片类药物的止痛 当联合给药时，滥用倾向和止痛。 这项拟议的研究将是对滥用责任和止痛有效性的首次检查。 高(~30：1)等(~1：1)和低(~1：30)THC：CBD比率的蒸发大麻，一种给药途径 与生态相关的THC：CBD比率。健康的大麻使用者(N=20，10M，10F)，有限 阿片类药物体验将完成8个门诊实验室会议，在此期间，他们将接受亚 Oxy(2.5毫克)或安慰剂，然后吸入30：1，1：1，1：30 THC：CBD，或 安慰剂大麻蒸气通过Volcano®雾化器。30：1剂量将在总THC含量上与1：1剂量匹配， 但含有1毫克CBD；1：30剂量的CBD总量将与1：1剂量相当，但含有1毫克CBD 太好了。这一设计使我们能够检查THC和CBD对措施的独立和联合影响 单独给药时的滥用责任(积极的主观影响，自我管理)和止痛 当与Oxy结合时。在有效减少RxOps治疗剂量和滥用风险的同时 治疗疼痛是公共卫生的优先事项。大麻类药物有希望，但令人担忧的是缺乏 科学数据，以告知它们是否减轻或增强不利影响。拟议的研究将紧急提供 需要关于THC和CBD对滥用倾向、医用大麻的治疗效用和 大麻类药物治疗慢性疼痛，以及与RxOps联合使用时的效果。

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.