Ligresti Alessia, Petrosino Stefania, Di Marzo Vincenzo
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.
Curr Opin Chem Biol. 2009 Jun;13(3):321-31. doi: 10.1016/j.cbpa.2009.04.615. Epub 2009 Jun 3.
The discovery of the endocannabinoid signalling system, that is, of cannabinoid receptors, their endogenous ligands, known as endocannabinoids, and of endocannabinoid anabolic and catabolic enzymes, raised several questions regarding the physiopathological role of these mediators. Several of these questions were answered by investigating alterations in the levels of the most studied endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in tissues of animal models of disorders, and in bioptic samples and biological fluids (cerebrospinal fluid and blood) of human volunteers. Subsequently, the pharmacological effects of synthetic compounds that selectively target the cannabinoid CB(1) and CB(2) receptors, and endocannabinoid anabolic and catabolic enzymes, established cause-effect relationships between pathological alterations in endocannabinoid levels and the symptoms and progress of several disorders, including emesis, obesity, metabolic disorders, hepatic diseases, pain, inflammation and neurological and neuropsychiatric disorders. These new developments are discussed in this second review on the endocannabinoids, together with the results of pre-clinical and clinical studies on the potential therapeutic use of plant-derived cannabinoids and synthetic agents that manipulate pharmacologically the action at cannabinoid receptors or the tissue levels of AEA and 2-AG.
内源性大麻素信号系统的发现，即大麻素受体、其被称为内源性大麻素的内源性配体以及内源性大麻素合成和分解代谢酶的发现，引发了关于这些介质生理病理作用的若干问题。通过研究疾病动物模型组织以及人类志愿者活检样本和生物体液（脑脊液和血液）中研究最多的内源性大麻素——花生四烯酸乙醇胺（AEA）和2-花生四烯酸甘油酯（2-AG）水平的变化，其中一些问题得到了解答。随后，选择性靶向大麻素CB(1)和CB(2)受体以及内源性大麻素合成和分解代谢酶的合成化合物的药理作用，确立了内源性大麻素水平的病理改变与包括呕吐、肥胖、代谢紊乱、肝脏疾病、疼痛、炎症以及神经和神经精神疾病在内的多种疾病的症状及进展之间的因果关系。在这第二篇关于内源性大麻素的综述中，将讨论这些新进展，以及关于植物源性大麻素和通过药理学手段调控大麻素受体作用或AEA和2-AG组织水平的合成药物潜在治疗用途的临床前和临床研究结果。
