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.