Butler Helen, Korbonits Márta
Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Eur J Endocrinol. 2009 Nov;161(5):655-62. doi: 10.1530/EJE-09-0511. Epub 2009 Sep 3.
The endocannabinoid system has emerged as a significant player in the control of energy balance and metabolism, through its direct central and peripheral effects, as well as via its interaction with other appetite-regulating pathways. There is mounting evidence that the endocannabinoid system is overactive in obesity and were it possible to safely dampen-down the elevated endocannabinoid tone, lipid and carbohydrate profiles could be improved and weight loss induced. The series of randomised clinical trials showed reproducible beneficial effects on weight, HbA1c and lipid parameters, in addition to other cardiovascular risk factors. However, to date, clinical developments have been halted because of psychiatric side effects. Although recent evidence has highlighted the importance of an appetite-independent, peripheral mode of action, it is still unclear whether selectively blocking the peripheral system could potentially solve the problem of the central side effects, which thus far has led to the demise of the cannabinoid antagonists as useful pharmaceuticals. In this concise review, we summarise the data on the metabolic effects of the cannabinoid pathway and its antagonists.
内源性大麻素系统已成为能量平衡和代谢控制中的重要参与者，它通过直接的中枢和外周作用，以及与其他食欲调节途径的相互作用来发挥作用。越来越多的证据表明，内源性大麻素系统在肥胖中过度活跃，如果能够安全地降低升高的内源性大麻素水平，脂质和碳水化合物状况可能会得到改善，并诱导体重减轻。一系列随机临床试验显示，除了其他心血管危险因素外，对体重、糖化血红蛋白和脂质参数具有可重复的有益作用。然而，迄今为止，由于精神方面的副作用，临床研究进展已停止。尽管最近的证据强调了食欲非依赖性外周作用模式的重要性，但目前仍不清楚选择性阻断外周系统是否有可能解决中枢副作用问题，而这一问题迄今为止已导致大麻素拮抗剂作为有用药物的研发失败。在这篇简要综述中，我们总结了有关大麻素途径及其拮抗剂代谢作用的数据。
