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

急性大麻给药对类风湿关节炎患者疼痛症状和炎症标志物的影响

• 批准号: 10259693
• 负责人: Elizabeth Aston
• 金额: $ 27.47万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259693
• 关键词: Acute; Address; Adult; Affect; Age; Alternative Therapies; American; Analgesics; Animal Model; Anti-Inflammatory Agents; Antiinflammatory Effect; Area; Arthritis; Biological Markers; Blood; Cannabidiol; Cannabinoids; Cannabis; Cells; Clinical; Clinical Research; Clinical Treatment; Crossover Design; Cytokine Suppression; Dependence; Diagnosis; Dose; Double-Blind Method; Formulation; Human; Individual; Induction of Apoptosis; Inflammation; Inflammatory; Inhibition of Cell Proliferation; Interleukin-1; Interleukin-1 alpha; Interleukin-1 beta; Interleukin-6; Ligands; Literature; Malignant Neoplasms; Medical Marijuana; Multiple Sclerosis; Opioid; Outcome; Pain; Pain management; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Physiological; Pilot Projects; Placebos; Plants; Population; Production; Property; Proteins; Randomized Controlled Trials; Recommendation; Reporting; Research; Rheumatoid Arthritis; Sleep; Statutes and Laws; Surveys; Swelling; Symptoms; TNF gene; Testing; Tetrahydrocannabinol; Time; United States; Work; addiction; associated symptom; chronic inflammatory disease; chronic pain; chronic painful condition; cytokine; disorder risk; experience; improved; inflammatory marker; joint destruction; joint injury; loss of function; marijuana legalization; marijuana use; negative affect; negative mood; novel; pain reduction; pain symptom; painful neuropathy; pre-clinical research; preclinical study; psychological symptom; reduce symptoms; side effect; symptom treatment; synergism; treatment guidelines; vapor; vaporization

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.

项目总结 大麻据称是几种慢性疼痛诊断的有效药物疗法，包括 多发性硬化症、神经性疼痛和癌症相关疼痛。然而，缺乏良好的控制。 使用大麻治疗类风湿性关节炎(RA)相关症状的研究。RA是一种慢性病 影响大约130万美国人的炎症性疾病，这个数字正在增加，因为美国 人口老龄化。RA的特征是关节破坏、僵硬、肿胀和疼痛，导致关节丧失 功能。此外，关键的细胞因子或致炎分泌蛋白与关节损伤有关。 与类风湿关节炎有关；具体地说，是肿瘤坏死因子-α和白介素1。临床前研究表明，大麻类药物显示 在类风湿性关节炎患者的人类细胞和类风湿性关节炎的动物模型中都具有良好的抗关节炎特性。只有一个 一项临床研究调查了一种大麻植物衍生品的效果，这种大麻植物衍生品由两个等量的比例组成 口腔粘膜形式的大麻素(即Δ⁹-四氢大麻酚和大麻二酚)对疼痛相关的作用 给RA，并报告了有希望的结果。全株大麻可能比合成大麻和部分大麻更有效 治疗慢性疼痛条件的制剂，推定是由于其数百种不同的成分 协同作用缓解症状的大麻素。除了THC，它已经被证明减少了 几种类型的慢性疼痛，CBD可能在减少RA的阴性症状方面特别有效 患者由于其抗炎特性。这一试点项目将调查大麻对 RA患者的疼痛、情感和炎症(n=66)。我们将通过以下途径管理三种大麻配方 汽化(安慰剂，低THC[1%]/中CBD[1-5%]，中THC[1-5%]/中CBD[1-5%]) 三个实验阶段采用平衡、双盲、交叉设计。我们将采集血液 每次疗程(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同一时间点进行评估。大麻对疼痛、情感和 将对炎性生物标志物进行评估。这项研究将是第一次研究这种剂量依赖效应。 大麻对类风湿关节炎患者疼痛、情感和炎症标志物的影响。探索新奇而有效的 就目前而言，减少RA患者疼痛和炎症的策略至关重要 药物疗法可能不能完全缓解阴性症状，包括阿片类药物在内的一些药物表现得很高。 依赖责任。随着各州继续将用于医疗和娱乐目的的大麻合法化，它是 对于医生治疗个人的疾病，为国家立法和临床治疗指南提供信息是必不可少的 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 关于大麻配方的准确建议。