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：
9895190
负责人：
JENNY L. WILEY
金额：
$ 48.76万
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/9895190
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 off-patent pain behavior pain patient pain perception pain relief pain sensation painful neuropathy phytocannabinoid pre-clinical preclinical evaluation receptor receptor binding sciatic nerve screening urinary

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 off-patent pain behavior pain patient pain perception pain relief pain sensation painful neuropathy phytocannabinoid pre-clinical preclinical evaluation receptor receptor binding sciatic nerve screening urinary

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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.

项目摘要通过记录的历史，人类将天然产品用于医疗目的。随着现代的分析和药物方法，其中一些“自然疗法”中的主动侵害是确定并成为药物开发工作中的基础化学品。在众多示例中，阿司匹林（柳树的树皮），辣椒素（辣椒）和阿片类药物（罂粟植物）是他们的镇痛特性。与这些其他天然产品类似，大麻sativa长期以来被用于医学目的，包括缓解疼痛。大麻植物（Cannabis sativa/Indica）包含100多个植物大麻素以及其他500多种其他鉴定的化学物质，包括给大麻的萜类化学物质独特的调味和香气。然而，超出了9-thc和cbd，难以识别，孤立和纯化的次要植物大麻素的数量足以体内评估，已阻碍了适当的研究单个植物大麻素的潜在治疗用途。最近，我们确保了访问权限纯化的次要大麻素是通过量的专利生物合成过程合成的临床前体内测试。拟议项目的目的是对这些项目进行全面评估单独使用化合物，并在计划的组合中确定其作为镇痛药的潜在有效性。此外，我们将对大麻植物中已鉴定的选定萜烯进行平行研究。小说需要采取镇痛策略来对抗阿片类药物的过度依赖和次要后果依赖性和发病率/死亡率。