1.0 Introduction
Ethnopharmacological studies have shown the use of Cannabis sativa in traditional medicine for over a thousand years, with its widespread use promoted by its psychotropic effects (McCoy, 2016; Turcotte et al., 2016). The discovery of a receptor within human body, that is selectively activated by cannabinoids suggested the presence of at least one endogenous ligand for this receptor. This is confirmed by the discovery of two endogenously synthesized lipid mediators, 2-arachidonoyl-glycerol and arachidonoylethanolamide, which function as high-affinity ligands for a subfamily of cannabinoid receptors ubiquitously distributed in the central nervous system, known as the CB1 receptors (Turcotte et al., 2016). A second cannabinoid receptor, the CB2, has since been cloned, characterised and discovered to be primarily distributed in immune cells with some level of expression in the brain (Munro et al., 1993). CB2 receptor is thus believed to be involved in immunomodulation following activation by cannabinoids and endocannabinoids (Galiegue et al., 1995). Collectively, endocannabinoids and their receptors, together with enzymes responsible for the synthesis and metabolism of endocannabinoids, constitute the endocannabinoid system (Zeng et al., 2019; Turcotte et al., 2016).
The endocannabinoid system plays crucial roles in critical processes involved in the normal physiology of the body, such as immune function. It also plays a role in pathological processes such as neuroinflammation, neoplastic diseases, cardiovascular diseases, ulcerative colitis, anxiety, depression and pain (Ligresti et al., 2009; McPartland et al., 2014). Activation of the CB2 receptor has been reported to be associated with positive outcomes in atherosclerosis, ischemic reperfusion injury and multiple sclerosis (Wen et al., 2015; Zhao et al., 2010). Understanding the mechanisms involved in cannabinoid receptor-mediated modulation of homeostatic and defensive functions and the various signaling pathways associated, will aid in the development of ligands that can selectively modulate cannabinoid receptor activity in the management of inflammatory and immune disorders. Thus, in this review, we discuss the role of cannabinoid receptor activation in inflammation and immunobiology.