The Endocannabinoid System and How It Works

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The endocannabinoid system refers to a group of neuromodulatory lipids and their receptors that are involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory; it mediates the psychoactive effects of cannabis and, broadly speaking, includes:

-The cannabinoid receptors CB1 and CB2, two G protein-coupled receptors that are located in the central and peripheral nervous systems, respectively.

-The endogenous arachidonate-based lipids, anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG); these are known as “endocannabinoids” and are physiological ligands for the cannabinoid receptors.

-The enzymes that synthesize and degrade the endocannabinoids. Unlike traditional neurotransmitters, endogenous cannabinoids are not stored in vesicles after synthesis, but are synthesized on demand (Rodriguez de Fonseca et al., 2004).

However, some evidence suggests that a pool of synthesized endocannabinoids (namely, 2-AG) may exist without the requirement of on-demand synthesis.

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