Exploration of the lesser-known cannabinoids of Cannabis sativa

内源性大麻素系统广泛地由内源性大麻素、1型大麻素受体(CB1R)、2型大麻素受体(CB2R)、GPR18、GPR55、GPR119和瞬时受体势阳离子通道亚家族V1(TRPV1)以及多种酶组成。从大麻(大麻)中提取的植物来源的大麻素(也称为植物大麻素)可以改变内源性大麻素系统。最广为人知的植物大麻素是D9-四氢大麻酚(THC)和大麻二酚(CBD)。THC和CBD都因其治疗慢性和急性疼痛、癫痫、焦虑和调节食欲等效果而受到广泛研究。THC的药理作用比较成熟：THC是CB1R和CB2R的部分激动剂，是GPR18和GPR55的全激动剂。CBD的药理作用远没有那么清楚。CBD已被描述为CB1R负变构调节剂、CB2R部分激动剂、GPR18激动剂和GPR55拮抗剂等多种作用。除了THC和CBD，在大麻中还发现了至少90种其他植物大麻素。这些鲜为人知的植物大麻素的例子包括四氢大麻二酚酸、四氢大麻素(THCV)、大麻酚、大麻黄烯和大麻素(CBDV)。尽管已经进行了一些研究来证明这些化合物的一个子集--如三丙型丙型肝炎病毒和CBDV--在治疗癫痫等疾病中的潜在医疗价值，但大多数这些植物大麻素的生物学和受体介导的作用机制尚不清楚。这笔赠款的目标是与CanniMed治疗公司合作，分离这些鲜为人知的植物大麻素，并发现它们的作用机制(S)。在研究越来越多地集中在大麻的药用能力的时候，这项研究提供了一个关键的手段来确定不太为人所知的大麻类物质，即THC和CBD之外，如何影响细胞生物学。这项工作将有助于我们了解大麻如何影响身体，以便为政策、减少伤害和健康选择提供信息。

The endocannabinoid system is broadly composed of endogenous cannabinoids; type 1 cannabinoid receptor (CB1R), type 2 cannabinoid receptor (CB2R), GPR18, GPR55, GPR119, and transient receptor potential cation channel subfamily V 1 (TRPV1), and multiple enzymes. The endocannabinoid system can be altered by plant-derived cannabinoids from Cannabis (marijuana) (a.k.a phytocannabinoids). The most well-known phytocannabinoids are d9-terahydrocannabinol (THC) and cannabidiol (CBD). Both THC and CBD are being intensively studied for their potential to treat chronic and acute pain, epilepsy, anxiety, and modulating appetite, among other effects. The pharmacology of THC is relatively well-established: THC is a CB1R and CB2R partial agonist and a GPR18 and GPR55 full agonist. The pharmacology of CBD is far-less clear. CBD has been described as a CB1R negative allosteric modulator, CB2R partial agonist, GPR18 agonist, and GPR55 antagonist, among other effects. Beyond THC and CBD there are at least 90 other phytocannabinoids found in marijuana. Examples of these lesser-known phytocannabinoids include tetrahydrocannabidiolic acid, tetrahydrocannabivarin (THCV), cannabigerol, cannabichromene, and cannabivarin (CBDV). Although some studies have already been conducted to demonstrate the potential medical value of a subset of these compounds - such as THCV and CBDV - in treating conditions such as epilepsy, the biology and receptor-mediated mechanism of action for most of these phytocannabinoids is unknown. The goal of this grant is to work in collaboration with CanniMed Therapeutics Inc. to isolate these lesser-known phytocannabinoids and discover their mechanism(s) of action. At a time when research is increasingly focused on the medicinal capabilities of Cannabis, this research offers a critical means of determining how the lesser-known cannabinoids, that is other than THC and CBD, affect cellular biology. This work will contribute to our understanding of how Cannabis affects the body in order to inform policy, harms reduction, and health choices.