Beta-caryophyllene and cannabidiol combination: Chronic arthritis pain

项目摘要/摘要 慢性疼痛是成年人寻求医疗护理的最常见原因之一，已被认为与 行动不便和日常活动，焦虑和抑郁，以及自认为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。 可以通过开发新的和改进的治疗方法或更直接地获得更好的结果 通过确定现有或新兴药物的有利组合。这项研究提案将检验 一种涉及少量大麻素(大麻二酚，CBD)的新药物组合策略的有效性 和萜烯(β-石竹烯(ΒCP))，有效抑制慢性疼痛，没有滥用潜力。 在过去的几年里，由于CBD缺乏精神活性，它作为一种治疗剂受到了人们的关注。一个 在慢性疼痛模型中对CBD止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有潜力，表现出中等疗效。然而，有益的是 CBD的止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的止痛效果，而不存在潜在的 虐待。ΒCP已被美国食品和药物管理局批准为食品添加剂，因其 良好的安全状况。发现于罗勒、黑胡椒、丁香和大麻等植物中。BCP是一种 天然选择性大麻素2型受体激动剂(CB2)。在各种实验模型中，BCP具有 一种止痛作用而不会引起消极的精神反应，推测是由于其对CB2的选择性 同时，BCP确实有抗抑郁和缓解焦虑的作用，这是人们感兴趣的 解决慢性疼痛的常见并存问题。这个项目将检验新的假设，在比较中 单独使用中央商务区和业务控制点，中央商务区和ΒCP的组合产生了增强的(例如，协同) 无滥用潜在性慢性疼痛的止痛效果。目标1将使用行为分析和 确定CBD和ΒCP联合治疗慢性阻塞性肺疾病疗效的药理学工具 关节炎疼痛模型(完全弗氏佐剂，CFA)。我们将使用感官和行为评估 情感上的疼痛。等值分析将证明相互作用的性质(例如，协同作用)。虐待 还将测试中央商务区和ΒCP的组合潜力。 拟议的研究将显著影响慢性疼痛管理领域，提供一种新的 联合治疗，CBD和ΒCP，是有效的，不成瘾的。此外，如果有效的话，这种组合 治疗将对阿片类药物流行产生重大影响，因为它提供了一种安全的替代缺乏阿片类药物的药物 滥用的可能性。

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.