Anti-Inflammatory Properties of Cannabis Constituents

描述（由申请人提供）：本提案的总体长期目标是确定大麻（大麻）的单个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作用和诱导耐受性的限制。非精神活性大麻成分的存在和合成大麻素的发展鼓励进一步研究，以确定具有抗精神病特性的非精神活性植物成分。完整的大麻提取物（CME）和纯的非精神活性大麻素和非大麻素大麻成分将在人类全血模型中测试其影响体外炎症类花生酸和细胞因子产生的能力。 口服CME和纯非精神活性药物的抗精神病作用 还将在急性炎症模型（由大鼠皮下气囊中的IL-1 β和TNF α诱导）和慢性炎症模型（大鼠佐剂诱导的多关节炎）中测试大麻成分。用于体外实验和动物研究的对照将包括媒介物、地塞米松、吲哚美辛和环氧合酶2的选择性抑制剂。 一种非大麻素，非精神活性大麻成分称为cannflavin将使用高压液相色谱法分离，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利用大麻的重要生物学特性而不限制不良影响的方法。

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.