The endocannabinoid system (ECS) is a vital system composed of endocannabinoids, endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors (CBRs). Cannabinoid receptor proteins are dispatched throughout the vertebrate central nervous system (including the brain) and peripheral nervous system[1][2]. While the endocannabinoid system remains under preliminary research, it is involved in regulating physiological and cognitive processes. These include fertility,[3] pregnancy,[4] pre– and postnatal development,[5][6][7] various activity of the immune system,[8] appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis.[9][10]
Two primary cannabinoid receptors have been identified: CB1, first cloned in 1990; and CB2, cloned in 1993. CB1 receptors are found mostly in the brain, nervous system, peripheral organs, and tissues. They are the endogenous partial antagonist’s main molecular target, anandamide (AEA), and exogenous THC, the most known active cannabis component. Endocannabinoid 2-arachidonoylglycerol (2-AG), more abundant in the brain than AEA, acts as a full antagonist at both CB receptors.[11] CBD is a phytocannabinoid acting as a relatively weak antagonist at both CBRs and a more potent antagonist at TRPV1 and antagonist at TRPM8.[12] It is also known to be a negative allosteric modulator at CB1.[13] Overall, CBD can counteract some of the adverse side effects of THC.[14]
