Systematic Investigation of Rare Cannabinoids with Pain Receptors

具有疼痛感受器的稀有大麻素的系统研究

• 批准号: 9895356
• 负责人: Aditi Das
• 金额: $ 22.19万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895356
• 关键词: ARNT gene; Agonist; Analgesics; Anti-inflammatory; Area; Biological; Biological Assay; Biology; CNR1 gene; CNR2 gene; Calcium; Cannabidiol; Cannabinoids; Cannabis; Cations; Cells; Chemistry; Collaborations; Development; Drowsiness; Evaluation; Flavonoids; Future; GPR55 receptor; Goals; Human; Investigation; Kilogram; Knowledge; Letters; Libraries; Measurement; Measures; Methods; Microglia; Minor; Mission; National Institute of Drug Abuse; Outcome; Pain; Pain Research; Pain management; Pharmaceutical Preparations; Pharmacology; Phytochemical; Plant Extracts; Plant Sources; Plants; Property; Public Health; Receptor Activation; Reporting; Research; Sedation procedure; Structure; System; Terpenes; Testing; Tetrahydrocannabinol; Therapeutic; United States National Institutes of Health; Vanilloid; Work; base; beta-arrestin; cannabinoid receptor; chemical synthesis; clinical effect; innovation; milligram; neuroinflammation; next generation; novel; pain receptor; pain sensation; phytocannabinoid; programs; receptor; receptor expression; recruit; synthetic cannabinoid

PROJECT SUMMARY Remedies derived from the cannabis plants have been used for management of pain for centuries. Recent understanding of the clinical effects of cannabis and the corresponding cannabinoids in the treatment of pain has been focused on two major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Though effective, these compounds cause sedation and drowsiness. On the other hand, there are more than 110 known minor phytocannabinoids; however, only a few limited studies related to their analgesic properties exists to date. The major obstacle in studying rare cannabinoids is their limited availability. Numerous purifications of plant extracts mixtures usually provide only milligram quantities of pure compounds from kilograms of plant material, making such endeavors highly nonpractical as well as unsustainable. In fact, most of minor phytocannabinoids are not commercially available or listed in NIDA’s Drug Supply Program (DSP). As synthetic organic chemists and biologists, uniquely situated at the interface of chemistry and biology, our research programs are devoted to providing solutions to the supply problem in the form of sustainable and practical syntheses as well as performing fundamental biological studies. By providing an access to rare phytochemicals by synthetic means, we expect to remove the barrier of supply as a prerequisite for studying their analgesic properties. Specifically, this proposal describes synthetic approaches to several classes of rare phytocannabinoids and systematic evaluation of their anti-inflammatory potential in microglial cells. Minor cannabinoids with strong anti-inflammatory will undergo further evaluation towards their agonism/antagonism of major endogenous pain circuitry systems including cannabinoid receptors (CB1, CB2, GPR55) and vanilloid/transient receptor potential cation channel subfamily V (TRPV), subfamily A (TRPA), subfamily M (TRPM). It is expected that these studies will establish well-defined pharmacological properties of rare phytocannabinoids with respect to the major receptors involved in pain sensation.

项目摘要 几个世纪以来，源自大麻植物的疗法已用于管理疼痛。 了解大麻和相应大麻素在疼痛治疗中的临床作用 已经专注于两个主要的植物大麻素，即Delta-9-四氢大麻酚（THC）和大麻二酚（CBD）。 尽管有效，这些化合物会导致镇静和嗜睡。另一方面，不止 110个已知的小植物大麻素；但是，只有少数与其镇痛特性有关的有限研究 到目前为止存在。研究稀有大麻素的主要障碍是它们的可用性有限。很多的 植物提取物混合物的纯化通常仅提供毫克的纯化合物 大量的植物材料，使这种努力高度非实践和不可持续。实际上，大多数 小植物大麻素的次数无法在NIDA的药物供应计划（DSP）中列出或列出。作为 合成有机化学家和生物学家，独特地位于化学与生物学的界面，我们 研究计划致力于以可持续性的形式为供应问题提供解决方案 实际合成以及进行基本生物学研究。通过提供罕见的访问权限 植物化学物质通过合成方式，我们希望消除供应障碍作为研究的先决条件 这些提案描述了它们的镇痛特性。 植物大麻素和对小胶质细胞中其抗炎潜力的系统评估。次要的 具有强大抗炎药的大麻素将进一步评估其激动/对抗 主要的内源性疼痛电路系统，包括大麻素受体（CB1，CB2，GPR55）和 香草素/瞬态接收器潜在阳离子通道亚家族V（TRPV），亚家族A（TRPA），亚家族M （TRPM）。预计这些研究将建立明确的稀有药物特性 植物大麻素相对于涉及疼痛感觉的主要接收器。