内源性大麻素系统作为治疗靶点的利弊:30 年后的经验教训。

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2023-09-01 Epub Date: 2023-05-10 DOI:10.1124/pharmrev.122.000600
Mauro Maccarrone, Vincenzo Di Marzo, Jürg Gertsch, Uwe Grether, Allyn C Howlett, Tian Hua, Alexandros Makriyannis, Daniele Piomelli, Natsuo Ueda, Mario van der Stelt
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引用次数: 0

摘要

大麻衍生物大麻是西方世界使用最广泛的娱乐性药物,估计有 8,300 万人(占世界人口的 3%)吸食大麻。近年来,随着大麻在美国和世界许多州的合法化和医疗使用,社会对大麻风险的认识发生了显著转变。令人信服的研究证据以及美国食品和药物管理局批准将大麻二酚用于治疗严重的儿童癫痫,证实了大麻二酚、Δ9-四氢大麻酚和其他植物提取的大麻素(植物大麻素)具有巨大的治疗潜力。值得注意的是,我们的身体有一个由受体、代谢酶和转运体组成的复杂的内源性大麻素系统(ECS),它也受植物大麻素的调节。30 年前发现的第一种内源性大麻素是安乃近(N-arachidonoyl-ethanolamine);从那时起,ECS 的不同元素就成为药物设计计划的目标,目的是治疗(或至少减缓)中枢神经系统和外周的多种人类疾病。在此,我们将对 ECS 作为治疗靶点的利弊进行批判性回顾,以明确具有 ECS 活性的植物大麻素和以 ECS 为导向的合成药物对人类健康的益处。意义声明:内源性大麻素系统在人体内几乎无处不在地发挥着重要作用,要么参与中枢和外周疾病的关键过程,要么是治疗的靶点。因此,了解这一复杂系统各组成部分的结构、功能和药理学,特别是关键受体(如大麻素受体 1 和 2)和代谢酶(如脂肪酸酰胺水解酶和单酰基甘油脂肪酶)的结构、功能和药理学,将推动我们在分子、细胞和系统水平上对内源性大麻素信号和活性的了解,从而为治疗患者提供新的机会。
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Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.

The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research evidence and the Food and Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ9-tetrahydrocannabinol and other plant-derived cannabinoids (phytocannabinoids). Of note, our body has a complex endocannabinoid system (ECS)-made of receptors, metabolic enzymes, and transporters-that is also regulated by phytocannabinoids. The first endocannabinoid to be discovered 30 years ago was anandamide (N-arachidonoyl-ethanolamine); since then, distinct elements of the ECS have been the target of drug design programs aimed at curing (or at least slowing down) a number of human diseases, both in the central nervous system and at the periphery. Here a critical review of our knowledge of the goods and bads of the ECS as a therapeutic target is presented to define the benefits of ECS-active phytocannabinoids and ECS-oriented synthetic drugs for human health. SIGNIFICANCE STATEMENT: The endocannabinoid system plays important roles virtually everywhere in our body and is either involved in mediating key processes of central and peripheral diseases or represents a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of the components of this complex system, and in particular of key receptors (like cannabinoid receptors 1 and 2) and metabolic enzymes (like fatty acid amide hydrolase and monoacylglycerol lipase), will advance our understanding of endocannabinoid signaling and activity at molecular, cellular, and system levels, providing new opportunities to treat patients.

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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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