Discovered in the early 90s, the endocannabinoid system (SEC) is a physiological system made up of receptors, located mainly in the nervous system but also in peripheral tissues (organs, skin, bones, muscles, vascular system), and natural ligands called endocannabinoids or endogenous cannabinoids.
The endocannabinoid system (ECS) plays a major role in the equilibrium of the human body, as well as in mammals, birds, amphibians and other animal species.

How far have we got in researching this complex system that regulates our bodies?

History

It was during research on the phytocannabinoid (plant cannabinoid, exogenous) tetrahydrocannabinol (THC) in 1988 that the first endocannabinoid receptor, CB1 (type-1 cannabinoid receptor), was discovered. The aim of this research was to find the causes of the psychoactive and euphoric effects of tetrahydrocannabinol (THC), and it is this membrane receptor on the surface of the cells of our nervous system that explains the effects of this ligand. cannabinoid ligand. 

Following the discovery of this first endocannabinoid receptor CB1 (type-1 cannabinoid receptor), further studies were carried out to characterize it in 1990 on the rat brain, and researchers then turned their attention to the possibility that our bodies themselves produce (endogenous) cannabinoids. Following research on pig brains in 1992, anandamide or N-arachidonoyl-ethanolamine (A.E.A.) was the first endogenous cannabinoid to be detected, thus establishing that we do indeed possess an endocannabinoid system (ECS).

The second cannabinoid receptor, CB2 (type-2 cannabinoid receptor), was abstracted in 1993 from an ex-vivo cell culture, and is mainly found in immune system cells. Although less studied than CB1 for its inaction on the psychoactive effects of tetrahydrocannabinol (THC), CB2 explains the immunomodulatory effects of certain phytocannabinoids such as cannabidiol (CBD). In 1995, a second endocannabinoid, 2-arachidonoylglycerol (2-AG), like its counterpart, was detected in nervous system cells.

Endocannabinoid receptors

The two endocannabinoid receptors, CB1 (type-1 cannabinoid receptor) and CB2 (type-2 cannabinoid receptor), belong to the G-Protein-coupled receptor family. G Proteins are activated by ligands on the inner surface of cell membranes, thus binding to receptors- in other words, they enable the transfer of information between ligands and body cells via these receptors.

Endocannabinoid receptors are present in most of the body's cells, mainly those of the central nervous system. But they are also found in the digestive system, liver and pancreas, cardiovascular system, lungs, adipose tissue, adrenal glands, reproductive system, skin, bones and muscles.

In the central and peripheral nervous systems, CB1 receptors (type-1 cannabinoid receptor) are among the most representative G protein-coupled receptors. They are found in :

• Glial cells
• Neurons
• The cerebral cortex
• Thehippocampus
• Theamygdala 
• The basal ganglia 
• The substantia nigra pars reticulata
• The cerebellum
• The golbus pallidus
• The periaqueductal
• The ventrolateral medullary

   

CB1 (type-1 cannabinoid receptor) receptors are also detectable inperipheral organs and tissues:

• Striated muscle cells
• Leukocytes
• Endothelial cells (spleen, thymus and lymph nodes)
• Adipocytes
• The lungs
• The heart
• Gastrointestinal tra ct (small and large intestine, stomach, pancreas, liver)
• Urinary tra ct (kidneys and bladder)
• Reproductive organs
• Bones
• The joints
• The skin
• Adrenal glands
• The ciliary body
• The cornea

CB2 receptors (type-2 cannabinoid receptors) are mainly found in immune tissue:

• Leukocytes
• Mast cells
• Lymph nodes
• Theamygdala
• Spleen
• The thymus  

   

But also in :

• Bone marrow
• The liver
• The placenta
• The nervous system (central and peripheral)

These receptors are probably present in other cells of the body, but research is currently insufficient, particularly for CB2 (type-2 cannabinoid receptor) receptors, due to their non-affiliation with the psychoactive effects of tetrahydrocannabinol (THC). Research is currently underway following the detection of a third endocannabinoid receptor, GPR55.

Endogenous cannabinoids or endocannabinoids

The two main endocannabinoids,anandamide or N-arachidonoyl-ethanolamine (A.E.A.) and 2-arachidonoylglycerol (2-AG), are among the neurotransmitters that enable some form of communication between neurons, acting on them for good or ill. Formed from lipids contained in cell membranes, thesefatty acid derivatives, more specificallyarachidonic acid (omega-6), act both locally, in response to stimuli such as stress, and transiently, through rapid degradation in the body.

Anandamide or N-arachidonoyl-ethanolamine (A.E.A.) is affiliated to the CB1 (type-1 cannabinoid receptor) and has properties comparable to those of dopamine and serotonin, reproducing effects similar to those of tetrahydrocannabinol (THC) while retaining its own nature by inhibiting the permeability of intercellular junctions, the propagation of intercellular calcium signals and the emptying of intracellular calcium stores.

Like its counterpart, 2-arachidonoylglycerol (2-AG) reproduces effects comparable to those of tetrahydrocannabinol (THC), but has a greater affinity for CB2 (type-2 cannabinoid receptor) receptors, while also binding, albeit to a lesser extent, to CB1 (type-1 cannabinoid receptor) receptors. This ester is present in the brain 170 times more thananandamide.

Other endocannabinoids have been discovered, such asnoladine ether, virodhamine, N-arachidonyldopamine, H.E.A. and NADE, but further research is needed to determine their roles in the body and, of course, the likelihood of discovering others.

Functionalities of the endocannabinoid system (ECS)

The Theendocannabinoid system (ECS) is essential to thebody's equilibrium, playing a multitude of physiological roles such as :

• Neuronal plasticity
• Controlling emotions andappetite
• Learning skills
• Lipogenesis (fat cell formation)
• Hormonal stress management (adrenalin and corticosterone secretion)
• Cardiovascular system function (vasodilation and blood pressure).
• Control of intestinal motility and secretions in the digestive system
• Controllinginflammation and immune cell activity

   

But also on diseases such as :

• Inflammatory and immunological diseases (autoimmune diseases and allergies)
• Neurological and neuropsychological diseases
• Osteoporosis and cardiovascular pathologies
• Cancers
• Obesity and metabolic diseases

Conclusion

Researchers have noted a correlation between certain diseases and the increase or decrease of endocannabinoids in cells. Rebalancing the endocannabinoid system (ECS) by taking phytocannabinoids can regulate and balance the endocannabinoid system, helping to prevent, alleviate and even cure certain pathologies and serious illnesses. For greater efficacy of phytocannabinoidsa synergy between these hundreds of molecules and terpenes is necessary to preserve the "entourage effect".

Advances in research mean that the endocannabinoid system is much more extensive than previously thought. Further research is needed to uncover this highly complex system, which is one of the key players in thebalance of our bodies and those of most living beings.

Sources:

► INSERM: http://bit.ly/2VBtitB

► Nutrition: http://bit.ly/2LcQgTT

► NORML: http://bit.ly/2GVnVxs