FiIGURE 5 Components and functional role of endocannabinoid system
Endocannabinoids are endogenous metabolites of various eicosanoid fatty acids, act on cannabinoid receptors (CB1R and CB2R) (Al-Kuraishy et al., 2023) Moreover, endocannabinoids can interacts with other receptors including G-protein coupled receptors (GPRs) and vanilloid receptors (Kilaru & Chapman, 2020). CB1R is mainly expressed in the CNS, whereas CB2R is widely expresses the immune cells. However, CB2R is also expressed in the brainstem neurons and astroglia (Kilaru & Chapman, 2020). Endocannabinoid ligands such as anandamide or arachidonoyl ethanolmide (AEA) and 2-arachidonoyl glycerol (2-AG) are identified. AEA is synthesized from N-arachidonoyl-phosphatidylethanolamine (NAPE) via phospholipase A2, and degraded by fatty-acid amide hydrolase (FAAH) (Martinez Ramirez et al., 2023). 2-AG is generated from diacylglycerol by diacylglycerol lipase, and then converted to AA by monoacylglycerol (MGL) (Kilaru & Chapman, 2020) (Figure 6 ).