Effects of cannabidiol in chronic non-cancer pain on chronic opioid therapy

项目简介 越来越多的证据表明，内源性大麻素系统介导了神经元的 参与阿片类药物使用/成瘾和疼痛的过程。临床前和人类初步研究表明， 大麻二酚（CBD）可能有助于减少阿片类药物的使用和减轻CNCP患者的疼痛 综合征，但尚未进行CBD对CNCP维持的人的影响的研究。 COT。这项双盲、安慰剂对照、概念验证试验旨在比较口服 在40例CNCP综合征门诊患者中（未合并OUD），CBD 600 mg与安慰剂相比， 稳定的中剂量至高剂量阿片类镇痛药至少3个月，并有动机减少其 阿片类镇痛药维持剂量。试验持续时间为6个月，包括4个月的治疗 每日CBD 600 mg vs安慰剂治疗期（随机化后），随后停止研究2个月 药物或安慰剂。CBD的安全性和耐受性将在整个试验过程中进行评估。阿片类镇痛剂 将在基线和纵向评估维持剂量和疼痛。几种电位的变化 将测量治疗效应的介质（阿片类药物维持剂量的变化）（基线时和 纵向）包括：疼痛，心理领域（抑郁，焦虑，睡眠），改变的动机 阿片类维持药物的剂量和阿片类药物滥用/成瘾的标志物（即渴望、戒断） 症状）。CBD将在CNCP门诊患者的常规治疗（即COT）基础上给药 综合征这将是第一个探索CBD对CNCP综合征患者影响的临床试验 （没有OUD，但有发生OUD的风险），维持COT，并评估其安全性， 使用阿片类镇痛药。这项研究在使用CBD治疗阿片类药物方面具有高度创新性 在接受COT治疗的CNCP患者中使用域，试图减少与 中到高剂量COT。此外，它是创新的，因为生物多样性公约的行动机制， 不同于目前用于治疗疼痛的药物，也不同于用于治疗OUD的药物， 可能影响阿片类药物滥用/成瘾的基本神经生物学，包括减少中毒， 戒断、线索诱导的渴望和药物寻求行为、应激反应和冲动。动物 人体试验表明，持续的疾病缓解变化可能会因此而发生， CBD的治疗持续时间相对较短，这将代表一种新的方法， 药物干预以预防CNCP中COT的OUD。证明具有临床意义 接受中至高剂量COT的CNCP患者中阿片类药物使用和疼痛的减少可能具有 在减少不良后果（即阿片类药物成瘾和过量死亡）和改善 生活质量，以及推进慢性和慢性疾病之间的交叉的神经生物学基础的知识， 疼痛和阿片类药物使用/滥用。

Project Brief Summary There is growing evidence implicating the endogenous cannabinoid system in mediating neural processes involved in opioid use/addiction and pain. Preclinical and preliminary studies in humans suggest that cannabidiol (CBD) may be helpful in reducing opioid use and decreasing pain in patients with CNCP syndromes but no studies have yet been conducted of the effects of CBD in humans with CNCP maintained on COT. This double-blind, placebo-controlled, proof-of-concept trial is designed to compare effects of oral CBD 600mg to placebo in 40 outpatients with CNCP syndromes (without co-occurring OUD), maintained on stable moderate to high-dose opioid analgesics for a minimum of 3-months, and motivated to decrease their opioid analgesic maintenance dose. The trial duration will be 6-months and will include a 4-month treatment period (following randomization) of daily CBD 600mg vs placebo, followed by 2 months off of study medication or placebo. Safety and tolerability of CBD will be assessed throughout the trial. Opioid analgesic maintenance dose and pain will be assessed at baseline and longitudinally. Changes in several potential mediators of treatment effect (change in opioid maintenance dose) will be measured (at baseline and longitudinally) including: pain, psychological domains (depression, anxiety, sleep), motivation to change dose of opioid maintenance medication, and markers of opioid misuse/addiction (i.e. craving, withdrawal symptoms). CBD will be administered on top of treatment as usual (i.e. COT) for outpatients with CNCP syndromes. This would be the first clinical trial exploring the effects of CBD in patients with CNCP syndromes (without OUD but at risk for developing an OUD), maintained on COT, and to assess its safety when co- administered with opioid analgesics. The proposed study is highly innovative in using CBD to treat the opioid use domain in patients with CNCP on COT, in an attempt to reduce the potential harms associated with moderate to high-dose COT. Further, it is innovative because CBD has mechanisms of action that are different from medications currently used in the treatment of pain, and also in the treatment of OUDs which could affect the basic neurobiology of opioid misuse/addiction including reductions in intoxication, withdrawal, cue-induced craving and drug seeking behaviors, stress responsivity, and impulsivity. Animal and human trials suggest the possibility that sustained disease-modifying changes could occur as a result of relatively brief treatment duration with CBD, which would represent a novel approach in using a pharmacologic intervention to prevent OUD in CNCP on COT. Demonstration of clinically meaningful reductions in opioid use and pain in patients with CNCP on moderate to high-dose COT could have an enormous impact in reducing adverse outcomes (i.e. opioid addiction and overdose fatalities) and improving quality of life, as well as advancing knowledge of the neurobiological basis of the intersection between chronic pain and opioid use/misuse.