The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors (CBRs), and cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system (including the brain) and peripheral nervous system.[1][2] The endocannabinoid system remains under preliminary research, but may be involved in regulating physiological and cognitive processes, including fertility,[3] pregnancy,[4] pre- and postnatal development,[5][6][7] various activity of immune system,[8] appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis.[9][10] The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.[11]
Two primary cannabinoid receptors have been identified: CB1, first cloned (or isolated) in 1990; and CB2, cloned in 1993. CB1 receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endogenous partial agonist, anandamide (AEA), as well as exogenous THC, the most known active component of cannabis. Endocannabinoid 2-arachidonoylglycerol (2-AG), which was found to be two and three orders of magnitude more abundant in mammalian brain than AEA, acts as a full agonist at both CB receptors.[12] Cannabidiol (CBD) is a phytocannabinoid that acts as a rather weak antagonist at both CBRs and a more potent agonist at TRPV1 and antagonist at TRPM8.[13] It is also known to be a negative allosteric modulator at CB1.[14] CBD has been found to counteract some of the negative side effects of THC