Department of Pharmacology and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Neuroscience. 2012 Mar 1;204:207-29. doi: 10.1016/j.neuroscience.2011.11.020. Epub 2011 Nov 17.
The endocannabinoid signaling system is a widespread, neuromodulatory system in brain and is also widely utilized in the periphery to modulate metabolic functions and the immune system. Preclinical data demonstrate that endocannabinoid signaling is an important stress buffer and modulates emotional and cognitive functions. These data suggest the hypothesis that endocannabinoid signaling could be dysfunctional in a number of mental disorders. Genetic polymorphisms in the human genes for two important proteins of the endocannabinoid signaling system, the CB1 cannabinoid receptor (CB1R) and fatty acid amide hydrolase (FAAH), have been explored in the context of normal and pathological conditions. In the case of the gene for FAAH, the mechanistic relationships among the common genetic polymorphism, the expression of the FAAH protein, and its likely impact on endocannabinoid signaling are understood. However, multiple polymorphisms in the gene for the CB1R occur and are associated with human phenotypic differences without an understanding of the functional relationships among the gene, mRNA, protein, and protein function. The endocannabinoid ligands are found in the circulation, and several studies have identified changes in their concentrations under various conditions. These data are reviewed for the purpose of generating hypotheses and to encourage further studies in this very interesting and important area.
内源性大麻素信号系统是大脑中广泛存在的神经调节系统，在外周组织中也广泛用于调节代谢功能和免疫系统。临床前数据表明，内源性大麻素信号是重要的应激缓冲器，调节情绪和认知功能。这些数据表明，内源性大麻素信号在许多精神障碍中可能存在功能障碍。人类内源性大麻素信号系统两个重要蛋白的基因（CB1 大麻素受体 (CB1R) 和脂肪酸酰胺水解酶 (FAAH)）的遗传多态性已在正常和病理条件下进行了探索。就 FAAH 基因而言，常见遗传多态性、FAAH 蛋白的表达及其对内源性大麻素信号可能产生的影响之间的机制关系已经得到理解。然而，CB1R 基因的多个多态性与人类表型差异相关，但对基因、mRNA、蛋白和蛋白功能之间的功能关系还没有了解。内源性大麻素配体存在于循环中，已有多项研究在各种条件下检测到其浓度变化。本文旨在提出假说，并鼓励在这个非常有趣和重要的领域开展进一步研究，为此对这些数据进行了综述。
