Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses.
Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses.
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DOI：
10.3389/fphar.2021.777804
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发表时间：
2021
影响因子：
5.6
通讯作者：
Holmes AE
中科院分区：
文献类型：
--
作者：
Walsh KB;McKinney AE;Holmes AE
大麻的药用价值。可以追溯到几千年前的古代中国和埃及虽然大麻最近在治疗慢性疼痛和恶心方面表现出了希望，但由于大麻被列为附表1受控物质，对大麻的科学研究受到了限制。理解大麻药理学的一个重大突破是植物大麻素反式-Δ9-四氢大麻酚（Δ9-THC）和大麻二酚（CBD）的分离和表征。随后在20世纪90年代克隆了大麻素CB 1和CB 2受体，随后发现了内源性大麻素系统。除了主要的植物大麻素，Δ9-THC和CBD之外，大麻还产生超过120种其他大麻素，这些大麻素被称为次要和/或稀有大麻素。这些大麻素在植物中以较少量产生，并且与Δ9-THC和CBD一起沿着来自母体大麻素大麻萜酚酸（CBGA）。虽然我们目前对次要大麻素药理学的了解尚不完整，但研究表明，它们在多个靶点（包括CB 1和CB 2受体、瞬时受体电位（TRP）通道、过氧化物酶体增殖物激活受体（PPARs）、5-羟色胺5-HT 1a受体等）上起激动剂和拮抗剂的作用。由此产生的多种细胞信号传导途径的激活，结合其推定的协同活性，为其治疗作用提供了机制基础。最初的临床报告表明，这些大麻素可能在治疗神经性疼痛、神经退行性疾病、癫痫、癌症和皮肤病方面具有潜在的益处。本文重点介绍了次要大麻素的分子药理学，并强调了这些化合物的一些重要治疗用途。
The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.
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