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.

项目概要 几个世纪以来，源自大麻植物的药物一直被用于治疗疼痛。最近的 了解大麻和相应大麻素在治疗疼痛方面的临床效果 一直专注于两种主要的植物大麻素，δ9-四氢大麻酚（THC）和大麻二酚（CBD）。 这些化合物虽然有效，但会导致镇静和嗜睡。另一方面，还有超过 110 种已知的次要植物大麻素；然而，只有少数有关其镇痛特性的研究 迄今为止存在。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量的纯化合物 公斤植物材料，使得这种努力非常不切实际且不可持续。事实上，大多数 的次要植物大麻素尚未在市场上销售或列入 NIDA 的药品供应计划 (DSP)。作为 合成有机化学家和生物学家，独特地处于化学和生物学的交界处，我们 研究项目致力于以可持续和可持续的方式提供供应问题的解决方案 实际合成以及进行基础生物学研究。通过提供稀有资源 通过合成方式获得植物化学物质，我们希望消除供应障碍作为研究的先决条件 它们的镇痛特性。具体来说，该提案描述了几类稀有物质的合成方法 植物大麻素及其在小胶质细胞中的抗炎潜力的系统评估。次要的 具有强抗炎作用的大麻素将对其激动/拮抗作用进行进一步评估 主要的内源性疼痛电路系统，包括大麻素受体（CB1、CB2、GPR55）和 香草酸/瞬时受体电位阳离子通道亚科 V (TRPV)、亚科 A (TRPA)、亚科 M （TRPM）。预计这些研究将确定稀有药物的明确药理学特性 植物大麻素与涉及痛觉的主要受体有关。