Opioid and cannabinoid combinations in laboratory and clinical pain

阿片类药物和大麻素组合在实验室和临床疼痛中的应用

• 批准号: 9479123
• 负责人: Claudia Michelle Campbell
• 金额: $ 75.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9479123
• 关键词: Absence of pain sensation; Adjuvant; Adverse event; Affect; American; Analgesics; Animals; Attenuated; CNS processing; Cannabinoids; Chronic; Clinical; Clinical Data; Clinical Treatment; Clinical Trials; Cognitive; Confounding Factors (Epidemiology); Data; Degenerative polyarthritis; Dose; Double-Blind Method; Drug Combinations; Drug Evaluation; Drug Kinetics; Elderly; Evaluation; Evaluation Studies; FDA approved; Foundations; Human; Individual; Investigation; Knee Osteoarthritis; Laboratories; Laboratory Study; Literature; Measurement; Measures; Mediating; Methods; Modeling; N-Methylaspartate; Nature; Neurocognitive; Nociception; Opioid; Opioid Analgesics; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Performance; Pharmaceutical Preparations; Pharmacodynamics; Physical Function; Physiological; Placebos; Population; Public Health; Regimen; Reporting; Rodent; Safety; Sampling; Sensory; Signal Transduction; Stimulus; Testing; central sensitization; chronic pain; chronic pain patient; chronic painful condition; clinical pain; clinically relevant; cognitive performance; cohort; disability; drug testing; human subject; improved; indexing; opioid therapy; pain behavior; pain model; pain reduction; pre-clinical; transmission process

This laboratory study will evaluate whether a cannabinoid enhances the analgesic efficacy of an opioid in a clinical sample of chronic pain patients, laying the foundation for a larger clinical trial evaluating the utility of cannabinoids as potentially opioid-sparing adjuvants to chronic opioid therapy for pain. Heightened CNS processing, or central sensitization (CS), occurs across numerous chronic pain conditions and is an important treatment target in its own right. While cannabinoids show initial promise as treatments or adjuncts for some chronic pain conditions and pre-clinical data suggest effects on CS, little is known about the degree to which combining cannabinoids with opioids alleviates CS-mediated chronic pain. We propose a within-subject, single exposure, double-blind, placebo-controlled, human laboratory investigation of the extent to which a cannabinoid enhances opioid analgesia in a model chronic pain population (e.g., patients with knee osteoarthritis). Human laboratory studies are an ideal method for this initial evaluation because they provide the opportunity to tightly control study drug dosing and afford high sensitivity of measurements, and enable tight control of confounding variables that may otherwise exist in clinical treatment populations and could differentially impact outcomes. This approach will minimize the number of participants needed to determine whether a positive signal exists while permitting rigorous and elegant evaluation of the study aims. Primary study outcomes will include measures of clinical pain and central sensitization, physical function, drug effects (e.g., abuse liability, adverse events, cognitive performance), and pharmacokinetic analyses. The Aims will examine the magnitude and duration of cannabinoid/opioid combination in reducing clinical pain and central sensitization; the effects on physical functioning, adverse events and indices of abuse liability; and the pharmacokinetic and pharmacodynamics profiles for the individual and combined drugs. This study will provide the most systematic and rigorous evaluation of the potential for cannabinoids to enhance analgesic effects of opioids in human subjects to date, and will do so in a relevant and generalizable clinical pain population who has CS, which makes these results more directly relevant compared to studies conducted in healthy populations. These findings will be critical to informing the efficacy and safety profile for the advancement of opioid/cannabinoid combination regimens to clinical trials with chronic pain patients.

这项实验室研究将评估大麻素是否能增强阿片类药物的镇痛效果。 慢性疼痛患者的临床样本，为评估 大麻素作为慢性阿片类药物治疗疼痛的潜在阿片类药物保留佐剂。CNS升高 加工，或中枢致敏（CS），发生在许多慢性疼痛条件，是一个重要的 治疗目标本身。虽然大麻素显示出作为治疗或止痛药的初步承诺， 慢性疼痛状况和临床前数据表明对CS有影响，但对这种影响的程度知之甚少。 将大麻素与阿片样物质结合可减轻CS介导的慢性疼痛。我们提出了一个主题内，单一的 暴露、双盲、安慰剂对照、人体实验室研究， 大麻素增强模型慢性疼痛群体中的阿片样物质镇痛（例如，膝 骨关节炎）。人体实验室研究是这种初步评估的理想方法，因为它们提供了 有机会严格控制研究药物给药并提供高灵敏度的测量， 严格控制可能存在于临床治疗人群中的混杂变量， 不同的影响结果。这种方法将最大限度地减少参与者的数量， 是否存在积极信号，同时允许对研究目的进行严格和优雅的评估。初级 研究结果将包括临床疼痛和中枢致敏、身体功能、药物作用的测量 (e.g.,滥用倾向、不良事件、认知表现）和药代动力学分析。目标将 检查大麻素/阿片类药物组合在减轻临床疼痛和中枢神经系统疼痛方面的幅度和持续时间 敏感性;对身体功能、不良事件和虐待倾向指数的影响;以及 单个药物和联合药物的药代动力学和药效学特征。本研究将提供 对大麻素增强镇痛作用的潜力进行了最系统和严格的评估。 迄今为止，阿片类药物在人类受试者中的应用，并将在相关和可推广的临床疼痛人群中进行， 具有CS，这使得这些结果与在健康人群中进行的研究相比更直接相关。 人口。这些研究结果对于为促进药物治疗的有效性和安全性提供信息至关重要。 阿片类药物/大麻素组合方案用于慢性疼痛患者的临床试验。