Minor Cannabinoids and Terpenes: Preclinical Evaluation as Analgesics

次要大麻素和萜烯：作为镇痛药的临床前评估

基本信息

批准号：
10015203
负责人：
JENNY L. WILEY
金额：
$ 47.05万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10015203
关键词：
Absence of pain sensation Acetic Acids Acids Acute Pain Adverse effects Analgesics Animal Model Aspirin Behavior Biological Assay Breeding CNR1 gene CNR2 gene Calcium Channel Cannabidiol Cannabinoids Cannabis Cannabis sativa plant Capsaicin Catalepsy Characteristics Chemicals Chili Pepper Dependence Development Dose Enzyme-Linked Immunosorbent Assay Evaluation Flavoring Foundations GTP-Binding Proteins Goals Human Individual Inflammation Injections Investigation Legal patent Ligation Mediating Mediation Metabolic Pathway Metabolism Methods Minor Modeling Modernization Morbidity - disease rate Motor Activity Mus Natural Products Natural Remedy Opioid Opium Orphan Pain Pain Measurement Papaver Peripheral Pharmaceutical Preparations Pharmacologic Substance Plants Procedures Process Property Receptor Activation Receptor Signaling Recording of previous events Rodent Secure Signal Transduction Stretching TRP channel Tail Terpenes Testing Tetrahydrocannabinol Therapeutic Effect Therapeutic Uses Treatment Efficacy Trees Urine Visceral pain Willow cannabimimetics combat cytokine drug development drug discrimination experimental study in vivo evaluation inflammatory pain mortality mouse model mu opioid receptors natural hypothermia non-opioid analgesic novel pain behavior pain patient pain perception pain relief pain sensation painful neuropathy phytocannabinoid pre-clinical preclinical evaluation receptor receptor binding sciatic nerve screening urinary

项目摘要

PROJECT SUMMARY Throughout recorded history, humans have used natural products for medicinal purposes. With the onset of modern analytical and pharmaceutical methods, the active ingredients in some of these “natural remedies” were identified and became foundational chemicals in drug development efforts. Among the numerous examples, aspirin (bark of the willow tree), capsaicin (chili peppers), and opioids (opium poppy plant) are notable for their analgesic properties. Similar to these other natural products, Cannabis sativa has long been used for medicinal purposes, including pain relief. The cannabis plant (Cannabis sativa/indica) contains over 100 phytocannabinoids as well as over 500 other identified chemicals, including the terpenoids that give cannabis its distinctive flavoring and aroma. Beyond 9-THC and CBD, however, difficulties in identifying, isolating and purifying minor phytocannabinoids in quantities sufficient for in vivo evaluation have hampered adequate investigation of potential therapeutic uses of individual phytocannabinoids. Recently, we have secured access to purified minor cannabinoids synthesized via a patented biosynthetic process in quantities that allow for preclinical in vivo testing. The goal of the proposed project is to provide a comprehensive evaluation of these compounds alone, and in planned combinations, to determine their potential efficacy as analgesics. In addition, we will conduct a parallel investigation of selected terpenes that have been identified in the cannabis plant. Novel analgesic strategies are needed to combat over-reliance on opioids and the resulting secondary consequences of dependence and morbidity/mortality.

项目概要纵观有记载的历史，人类一直将天然产品用于医疗目的。现代分析和制药方法，其中一些“自然疗法”的活性成分是在众多例子中，确定并成为药物开发工作的基础化学品。阿司匹林（柳树皮）、辣椒素（辣椒）和阿片类药物（罂粟植物）以其功效而闻名。与这些其他天然产品类似，大麻长期以来一直用于药用。大麻植物（Cannabis sativa/indica）含有 100 多种成分。植物大麻素以及超过 500 种其他已确定的化学物质，包括赋予大麻其功效的萜类化合物然而，除了 9-THC 和 CBD 之外，识别、分离和鉴定也存在困难。纯化微量植物大麻素的数量足以进行体内评估已妨碍充分最近，我们已经获得了对单个植物大麻素的潜在治疗用途的调查。通过专利生物合成工艺合成的纯化次要大麻素，其数量允许拟议项目的目标是对这些进行综合评估。单独的化合物以及计划的组合，以确定它们作为镇痛药的潜在功效。我们将对大麻植物中发现的选定萜烯进行平行调查。需要采取镇痛策略来对抗对阿片类药物的过度依赖以及由此产生的继发后果依赖性和发病率/死亡率。