Impact of Acute Cannabis Administration on Pain Symptomology and Inflammatory Markers among Patients with Rheumatoid Arthritis

项目摘要 大麻据称是一种有效的药物治疗几种慢性疼痛的诊断，包括 多发性硬化症、神经性疼痛和癌症相关疼痛。然而，缺乏控制良好的 研究使用大麻治疗与类风湿性关节炎（RA）相关的症状。RA是一种慢性 炎症性疾病影响了大约130万美国人，随着美国的发展， 人口老龄化。类风湿关节炎的特征是关节破坏、僵硬、肿胀和疼痛，导致关节功能丧失。 功能此外，关键的细胞因子，或促炎分泌蛋白，参与关节损伤 与RA相关;特别是TNF-α和IL-1。临床前研究表明，大麻素 在来自RA患者的人细胞和RA动物模型中具有有希望的抗关节炎特性。只有一 一项临床研究调查了大麻植物衍生物的效果， 大麻素（即，Δ α-四氢大麻酚[THC]和大麻二酚[CBD]），以乳清酸形式，对疼痛相关 RA，并报告了有希望的结果。全植物大麻可能比合成和部分大麻更有效。 制剂治疗慢性疼痛的条件下，puerestine由于其组成的数百个不同的 大麻素协同作用缓解症状。除了THC，它已被证明可以减少 对于几种类型的慢性疼痛，CBD可能在减少RA的负性神经病学方面特别有效 患者由于其抗炎特性。该试点项目将调查大麻对 RA患者的疼痛、情感和炎症（n = 66）。我们将通过以下方式管理三种大麻制剂： 汽化（安慰剂，低THC [<1%] /中等CBD [1-5%]，中等THC [1-5%]/中等CBD [1-5%]） 三个实验阶段，使用平衡、双盲、交叉设计。将采集血液 每次治疗期间（汽化前、汽化后10分钟、汽化后60分钟）。自我- 报告的疼痛和影响将在相同的时间点进行评估。大麻对疼痛的影响，影响， 将评估炎性生物标志物。这项研究将是第一个调查剂量依赖性效应 大麻对RA患者疼痛、情感和炎症标志物的影响。探索新颖有效 减少RA患者疼痛和炎症的策略至关重要， 药物治疗可能不能完全缓解阴性症状，有些药物，包括阿片类药物， 依赖责任。随着各州继续将大麻合法化用于医疗和娱乐目的， 必须告知州立法和临床治疗指南，供医生治疗患有 慢性疼痛这项研究有可能指导有关使用大麻治疗RA的临床决策 关于大麻制剂的精确建议。

PROJECT SUMMARY Cannabis is purported to be an effective pharmacotherapy for several chronic pain diagnoses, including multiple sclerosis, neuropathic pain, and cancer-related pain. However, there is a dearth of well-controlled research on use of cannabis to treat symptoms associated with rheumatoid arthritis (RA). RA is a chronic inflammatory disease that affects approximately 1.3 million Americans, a number that is increasing as the US population ages. RA is characterized by joint destruction, stiffness, swelling, and pain, leading to loss of function. In addition, key cytokines, or pro-inflammatory secreted proteins, are involved in joint injury associated with RA; specifically, TNF-α and IL-1. Pre-clinical studies indicate that cannabinoids demonstrate promising anti-arthritic properties in both human cells from RA patients and animal models of RA. Only one clinical study has investigated the effect of a cannabis plant derivative comprised of an equal ratio of two cannabinoids (i.e., Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]), in oromucosal form, on pain related to RA, and reported promising results. Whole plant cannabis may be more effective than synthetic and partial formulations to treat chronic pain conditions, putatively due to its composition of hundreds of distinct cannabinoids that work in synergy to alleviate symptoms. In addition to THC, which has been shown to reduce several types of chronic pain, CBD may be particularly effective in reducing negative symptomology in RA patients due to its anti-inflammatory properties. This pilot project will investigate the impact of cannabis on pain, affect, and inflammation among RA patients (n = 66). We will administer three cannabis formulations via vaporization (placebo, low THC [<1%] /medium CBD [1-5%], medium THC [1-5%]/medium CBD [1-5%]) across three experimental sessions using a counter-balanced, double-blind, crossover design. Blood will be collected during each session (pre-vaporization, 10 minutes post-vaporization, 60 minutes post-vaporization). Self- reported pain and affect will be assessed at the same time points. The effect of cannabis on pain, affect, and inflammatory biomarkers will be assessed. This study will be the first to investigate the dose-dependent effect of cannabis on pain, affect, and markers of inflammation among patients with RA. Exploring novel and effective strategies to reduce pain and inflammation among individuals living with RA is crucial as current pharmacotherapies may not completely alleviate negative symptoms, and some, including opioids, pose high dependence liability. As states continue to legalize cannabis for medical and recreational purposes, it is essential to inform both state legislation and clinical treatment guidelines for physicians treating individuals with chronic pain. This study has the potential to guide clinical decisions pertaining to use of cannabis to treat RA symptoms with precise recommendations regarding cannabis formulation.