Endocannabinoid system (ECS) is the interaction between cannabinoids and the receptors in the human body which is a communication system between cells. It is a neurotransmission system found in different zones and tissues of our body helping in the regulation of various metabolic processes. And it is a key role in regulating pain, appetite, immune function, and dozens of other physiological processes. This system regulates such diverse functions as memory, digestion, motor function, immune response, inflammation, appetite, pain, blood pressure, bone growth, and the protection of neural tissues. The ECS comprises three principal elements: endocannabinoid receptors, endocannabinoids (interacting with the receptors), and enzymes (either synthesized or metabolized).

Endocannabinoid receptors which are found throughout the body, bind to endocannabinoids in order to signal and take action. There are two main endocannabinoid receptors: CB1 receptors, which are mostly found in the central nervous system and; CB2 receptors, which are mostly found in your peripheral nervous system, especially immune cells. Endocannabinoids can bind to either receptor. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

 

In the brain, the CB1 receptor is expressed and combined to form a circuit breaker modulating the releases of inhibitory and excitatory neurotransmitters across the synapse as called the activation of CB1 receptor. It is responsible for the psychoactive effects of cannabis due to the THC mimicking an endocannabinoid by binding to the CB1 receptor.  In the case of CB2, it is only primarily found in immune and blood cells, tonsils, and the spleen controlling the release of secreted cytokines or immunoregulatory proteins which link to the inflammation and general immune function through the body. The CB2 expression has been identified in key regions of brain including the hippocampus showing the modulation of midbrain such as the self-administration of cocaine.2 In the hippocampus, CB2 receptor also modulates the self-activity and information flow between brain networks, potentially assisting in the selection of inputs that may guide complex behaviors.

 

The endocannabinoid system has been shown to have a  homeostatic role by controlling several metabolic functions, such as energy storage and nutrient transport. It acts on peripheral tissues such as  adipocytes,  hepatocytes, the  gastrointestinal tract , the  skeletal muscles and the endocrine  pancreas . It has also been implied in modulating  insulin sensitivity .  Through all of this, the endocannabinoid system may play a role in clinical conditions, such as  obesity,  diabetes, and  atherosclerosis , which may also give it a  cardiovascular role .

 

Reference

1. Backes, M., Cannabis pharmacy: the practical guide to medical marijuana: Revised and Updated. Hachette UK: 2017.

2. Zhang, H.-Y.;  Gao, M.;  Liu, Q.-R.;  Bi, G.-H.;  Li, X.;  Yang, H.-J.;  Gardner, E. L.;  Wu, J.; Xi, Z.-X., Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proceedings of the National Academy of Sciences 2014, 111 (46), E5007-E5015.

3. Stempel, A. V.;  Stumpf, A.;  Zhang, H.-Y.;  Özdoğan, T.;  Pannasch, U.;  Theis, A.-K.;  Otte, D.-M.;  Wojtalla, A.;  Rácz, I.; Ponomarenko, A., Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus. Neuron 2016, 90 (4), 795-809.

4. Quraishi, S. A.; Paladini, C. A., A central move for CB2 receptors. Neuron 2016, 90 (4), 670-671.

5. Bellocchio L, Cervino C, Pasquali R, Pagotto U (June 2008).  "The endocannabinoid system and energy metabolism" . Journal of Neuroendocrinology. 20 (6): 850–7.