The Endocannabinoid System

The endocannabinoid system was discovered in the 1990s. It is a system that is found in many parts of the human body. It consists of cannabinoid receptors and humanly produced ligands, so called endocannabinoids, as well as enzymes that break down the endocannabinoids.

The two most known endocannabinoids are anandamide and 2-arachidonoylglycerol (2-AG). The most common and most researched receptors are CB1 and CB2, but there are also additional cannabinoid receptors including nuclear receptors (PFAR’s) and TRPV1 channels. The endocannabinoids can also interact with other cellular targets, but the significance of these interactions remains to be determined.

Belonging to the system are also enzymes for the biosynthesis and degradation of the endocannabinoids, most studied are the fatty acid amide hydrolase (FAAH) and mono acylglyrecol lipase (MAGL). The endocannabinoids are produced enzymes in the cell and since the system is relatively fast, degradation starts rather soon.

CB1 and CB2 can be found in the central nervous system and also in glands, in the liver and gametes and other places. The initial scientific understand was that CB1 was located in the central nervous system and CB2 in other parts of the body. Newer research has however indicated that CB2 receptors are to be found in a lesser degree in the central nervous system as well. CB2 receptors are also found on T cells of the immune system.

The endocannabinoid system regulates a variety of processes in the body, among them motor learning, appetite and pain sensation, stress control, homeostasis, anxiety, immune responses and much more. There is now a lot of research going to find out more, and it must be underlined that many of the processes, like stress control or homeostasis are complicated and complex processes in which many systems interact. Thus there is still a lot to be learned.

Over the past decade, primary interest has focused on CB1, for its role across a range of physiological functions, including directing the psychoactive effect of THC. Now scientific interest in the non-psychoactive substance CBD is growing rapidly.

CB1 is one of the most common G-protein coupled receptors in the central nervous system. Endocannabinoids themselves function as neuromodulators that are released by post-synaptic neurons, and bind to the presynaptic CB1s to moderate the release of neurotransmitters, such as gamma aminobutyric-acid (GABA), glutamate, and dopamine (DA). While the specific CB1 function depends on the cell population and region in which they reside, their role in retrograde signaling permits them to regulate signaling activity across cognitive, emotive, and sensory functions.

CB2 has been less well studied so far. While CB1 is mildly inducible, CB2 is highly inducible. CB2 seems to be a mediator of some of the anti-inflammatory actions of cannabinoids. A number of intriguing studies suggest CB2 may be a potential therapeutic target that can avoid the psycho activity of CB1 ligands.

Research on the ECS is ongoing with wide-ranging discoveries. The roles of endogenous cannabinoid, phytocannabinoids, and synthetic pharmacological agents acting on the various elements of the ECS have a potential to affect a wide range of pathologies, including food intake disorders, chronic pain, emesis, insomnia, glaucoma, gliomas, involuntary motor disorders, stroke, and psychiatric conditions such as depression, autism, and schizophrenia. Research into ECS's role in the stress response has revealed a significant influence on the hypothalamic–pituitary–adrenal axis, the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior.