Anti-Inflammatory Properties of Cannabis Constituents

描述(由申请人提供)：这项提案的总体长期目标是确定大麻的非精神活性成分单独或组合是否能为以急性和/或慢性炎症为特征的疾病提供安全、有效的治疗。大麻的药用受到其精神活动和耐受性的限制。非精神活性大麻成分的存在和合成大麻素的开发促进了进一步的研究，以确定具有抗炎特性的非精神活性植物成分。一种完整的大麻提取物(CME)以及纯的非精神活性大麻素和非大麻素类大麻成分将在人体全血模型中进行测试，以确定它们在体外影响炎性二十烷类和细胞因子产生的能力。 口服CME与单纯非精神病药的抗炎作用 大麻成分还将在急性炎症模型(由IL-1Beta和TNFpha在大鼠皮下气囊中诱导)和慢性炎症模型(佐剂诱导的大鼠多发性关节炎)中进行测试。体外实验和动物研究的对照药物将包括赋形剂、地塞米松、吲哚美辛和环氧合酶2的选择性抑制剂。一种名为大麻黄素的非大麻、非精神活性成分将通过高压液相色谱分离出来，并在体内模型和体外系统中进行测试。成功完成拟议的实验应该确定如何利用大麻的重要抗炎特性，而不会产生有限的不良影响。

DESCRIPTION (provided by applicant): The overall long term objective of this proposal is to determine whether individual nonpsychoactive constituents of Cannabis sativa (marijuana), alone or in combination, will provide safe, effective treatment for diseases characterized by acute and/or chronic inflammation. The medicinal use of marijuana has been limited by its psychoactivity and by induction of tolerance. Existence of nonpsychoactive marijuana constituents and development of synthetic cannabinoids encourage further research to identify nonpsychoactive plant components with antiinflammatory properties. A complete marijuana extract (CME) and pure nonpsychoactive cannabinoid and noncannabinoid Cannabis constituents will be tested in human whole blood models for their ability to influence production in vitro of inflammatory eicosanoids and cytokines. The antiinflammatory effects of oral administration of the CME and the pure nonpsychoactive Cannabis constituents will also be tested in a model of acute inflammation (induced by IL-1Beta and TNFalpha in a subcutaneous air pouch in rats), and a model of chronic inflammation (adjuvant induced polyarthritis in rats). Controls for experiments in vitro and studies in animals will include vehicle, dexamethasone, indomethacin, and a selective inhibitor of cyclooxygenase 2. A noncannabinoid, nonpsychoactive marijuana constituent termed cannflavin will be isolated using high-pressure liquid chromatography and tested in the in vivo models and in vitro systems. Successful completion of the proposed experiments should identify ways of harnessing important antiinflammatory properties of marijuana without the limiting adverse effects.