Beta-caryophyllene and cannabidiol combination: Chronic arthritis pain

β-石竹烯和大麻二酚组合：慢性关节炎疼痛

• 批准号: 10056530
• 负责人: Khalid Benamar
• 金额: $ 15.3万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056530
• 关键词: Address; Adult; Affective; Agonist; Analgesics; Anti Inflammatory Analgesics; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Attention; Behavior; Behavior assessment; Behavioral Assay; Beta-caryophyllene; Biological Assay; Black Pepper; CNR2 gene; Cannabidiol; Cannabinoids; Cannabis sativa plant; Caring; Chronic; Chronic inflammatory pain; Clove; Combined Modality Therapy; Development; Dose; Drug Combinations; Exhibits; Experimental Models; Female; Food Additives; Freund' s Adjuvant; Health; Hypersensitivity; Individual; Link; Mechanical Stimulation; Medical; Medical Care Costs; Mental Depression; Minor; Mus; Nature; Ocimum basilicum; Opioid; Outcome; Pain; Pain management; Persistent pain; Pharmaceutical Preparations; Pharmacology; Plants; Productivity; Quality of life; Research Proposals; Safety; Sensory; Terpenes; Testing; Therapeutic; Therapeutic Agents; Time; United States Food and Drug Administration; addiction; arthritic pain; base; behavioral pharmacology; chronic pain; chronic pain management; chronic painful condition; comorbidity; conditioned place preference; depressive symptoms; disability; effectiveness testing; improved; innovation; interest; male; new combination therapies; novel; opioid epidemic; pain model; pain reduction; pre-clinical; prescription opioid; programs; receptor; response; side effect; tool

PROJECT SUMMARY/ABSTRACT Chronic pain, one of the most common reasons adults seek medical care, has been linked to restrictions in mobility and daily activities, anxiety and depression, and poor perceived health or reduced quality of life. Treatment options are limited and often ineffective, contributing to current opioid prescription and abuse issues. Better outcomes can be achieved by developing new and improved therapeutic approaches or more immediately by identifying favorable combinations of available or emerging drugs. This research proposal will to test the effectiveness of a novel pharmacological combination strategy involving a minor cannabinoid (cannabidiol, CBD) and terpene (Beta-caryophyllene (ΒCP) to effectively inhibit chronic pain without abuse potential. CBD has gained attention as a therapeutic agent over the past several years due to its lack of psychoactivity. A preclinical dose-response study of the analgesic effect of CBD in a chronic pain model showed that although CBD has potential in managing chronic pain condition, it exhibited moderate efficacy. However, the beneficial analgesic effect of CBD was not associated with any of the common side effects of cannabinoids or abuse potential. Therefore, a strategy is needed to increase the analgesic efficacy of CBD without the potential for abuse. ΒCP has been approved by the Food and Drug Administration (FDA) as a food additive, known for its favorable safety profile. Found in plants including basil, black pepper, cloves, and cannabis sativa. BCP is a natural selective agonist for the cannabinoid type 2 receptor (CB2). In various experimental models, BCP has an analgesic effect without causing negative psychoactive effects, presumably due to its selectivity to the CB2 receptor; at the same time, BCP does have anti-depressant and anxiolytic effects which are of interest in addressing common comorbidities of chronic pain. This project will test the novel hypothesis that in comparison with CBD and BCP alone, CBD and ΒCP in combination produces an enhanced (e.g. synergistic) analgesic effect in chronic pain without abuse potential. Aim 1 will use behavioral assays and pharmacological tools to determine the beneficial of CBD and ΒCP in combination in the well-establish chronic arthritis pain model (Complete Freund’s Adjuvants, CFA). We will use the behavioral assessment of sensory and affective pain. Isobolographic analysis will demonstrate the nature of interaction (e.g. synergistic). The abuse potential of CBD and ΒCP in combination will also be tested. The proposed studies will significantly impact the field of chronic pain management by providing a new combination therapy, CBD and ΒCP, that is effective and nonaddictive. Furthermore, if effective, this combination therapy will have a significant impact on the opioid epidemic by offering a safe alternative to opioids that lacks abuse potential.

项目总结/摘要 慢性疼痛是成年人寻求医疗护理的最常见原因之一， 行动能力和日常活动、焦虑和抑郁、健康状况差或生活质量下降。 治疗选择有限，而且往往无效，导致目前的阿片类药物处方和滥用问题。 更好的结果可以通过开发新的和改进的治疗方法或更直接地实现 通过识别可用或新兴药物的有利组合。这项研究计划将测试 涉及少量大麻素（大麻二酚，CBD）的新型药理学组合策略的有效性 和萜烯（β-香紫苏烯（BCP）），以有效抑制慢性疼痛而没有滥用可能。 在过去的几年里，CBD作为一种治疗剂受到了关注，因为它缺乏精神活性。一 CBD在慢性疼痛模型中镇痛作用的临床前剂量反应研究表明，尽管 CBD在治疗慢性疼痛方面具有潜力，表现出中等疗效。然而，有益的 CBD的镇痛作用与大麻素或滥用的任何常见副作用无关 潜力因此，需要一种策略来增加CBD的镇痛功效，而没有潜在的 虐待BCP已被美国食品和药物管理局（FDA）批准为食品添加剂，以其 良好的安全性。存在于罗勒、黑胡椒、丁香和大麻等植物中。BCP是一个 大麻素2型受体（CB 2）的天然选择性激动剂。在各种实验模型中，BCP具有 镇痛作用而不引起负面精神活性作用，可能是由于其对CB 2的选择性 受体;同时，BCP确实具有抗抑郁和抗焦虑作用， 解决慢性疼痛的常见合并症。这个项目将测试一个新的假设， 单独使用CBD和BCP，CBD和BCP组合产生增强的（例如协同的） 对慢性疼痛有镇痛作用，无滥用可能。目标1将使用行为分析， 药理学工具，以确定CBD和BCP组合在良好建立的慢性 关节炎疼痛模型（完全弗氏佐剂，CFA）。我们将使用感官行为评估， 情感性疼痛等辐射线分析将证明相互作用的性质（例如协同作用）。滥用 CBD和BCP组合的潜力也将受到考验。 拟议的研究将通过提供一种新的治疗方法， 联合治疗，CBD和BCP，这是有效的和非成瘾性的。此外，如果这种组合有效， 治疗将对阿片类药物的流行产生重大影响，因为它提供了一种安全的阿片类药物替代品， 滥用潜力