The Endocannabinoid System

Here you will learn everything about the actual mechanism of action of endogenous cannabinoids, which are also called endocannabinoids. They are involved in various bodily functions and their production and degradation occurs not only in humans, but almost in the entire animal kingdom.

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„The human body is the most complex system ever created. The more we learn about it, the more appreciation we have about what a rich system it is."

BILL GATES

History

In the sixties and seventies, people wanted to understand the illegal drug THC and its mode of action more precisely. This led to the discovery of the endocannabinoid system in the human body. The first endocannabinoid "N-Arachidonylethanolamide" was discovered in the body in the late 90ies, and just a few years later, in 1995, the second endocannabinoid "2-Arachidonoylglycerol" was found.

Cannabinoid Receptors

Before the endocannabinoid system in our body was fully explored, it was assumed that cannabinoids had a similar mode of action to other drugs, such as alcohol, so a non-specific response. However, it soon became clear that - compared to the mode of action of alcohol - specific receptors are involved in this whole endocannabinoid system, and that it is therefore a specific mechanism.

CB1-Receptor

Since this receptor is not only found in the nervous system, but in almost all organs and tissues in our body, the slang term "brain cannabinoid receptor" is misleading. This has historical reasons, as it was previously assumed that the effect is only on the nervous system as well as in the brain. However, the number of receptors in the different tissues varies and in the brain, more precisely in the basal ganglia and the hippocampus, most receptors are present. The basal ganglia play a decisive role in the coordination of movements, while the hippocampus is crucial for spatial orientation and long-term memory.

The receptor is found in only low concentrations in the brainstem, which is responsible for controlling essential life functions such as respiration and circulation.  


An activation of this receptor protects the nervous system from overexcitation. This occurs through the inhibition of other neurotransmitters, substances that are released in the nervous system, such as acetylcholine, dopamine or serotonin. 

CB2-Receptor

Like CB1-receptors, CB2-receptors are found throughout the body. However, the highest number of these receptors are found on immune cells, such as macrophages and B-lymphocytes. Therefore, these receptors have a significant influence on the regulation of inflammatory activities in our body. In mammals, the CB2-receptors are particularly important in warding off harmful external influences, with the endocannabinoid system making an essential contribution.

Other Receptors

Various endocannabinoids can also bind to vanilloid receptors and other receptors. This leads to an even more complex system with diverse different endocannabinoids preferring different binding sites, and each binding or lack of these bindings can be related to a disease pattern.

Endocannabinoids

As explained above, the first two endocannabinoids, N-arachidonoylethanolamide (also called anandamide) and 2-arachidonoylglycerol, were discovered in the late 1990s. In addition, there are a large number of other endogenous cannabinoids that have structures similar to those mentioned above. However, many of them are not yet fully researched and therefore their function in our body is not yet completely clear.
The endocannabinoids are permanently produced and have a retroactive effect on the activity of neurotransmitters. In this sense, retroactive means that it is not the nerve cell, which usually transmits a signal, that produces the endocannabinoids, but the receiving cell. Endocannabinoids are increasingly released as soon as the concentration of neurotransmitters in the nervous system (such as dopamine, acetylcholine, noradrenaline) is increased. Thus, the cannabinoid receptors are increasingly activated, which in turn leads to inhibition of the activity of the neurotransmitters. 

If the normal functioning of the neurotransmitters is disturbed, this can be associated with various diseases in various organs. Therefore, the endocannabinoid system can also be part of diseases. In Tourette's syndrome, for example, the body tries to achieve self-healing via precisely this mechanism and thus eliminate the symptoms. In this case, the endocannabinoid system is strengthened. 
A lack of activity of this system has an influence on our body and can be involved in diseases. For example, this is the case with an Irritable Bowel Syndrome or with migraine. Reason for this could be heredity. 


About 200 anandamide-like subcances have been discovered in the brain only. Some of these substances bind exclusively to the CB1-receptor, others only to the CB2-receptor. Thus, the endocannabinoids can also be grouped, because depending on which receptor they bind to, this has a correspondingly different influence on the body and associated clinical patterns. 
The main task of the endocannabinoid system in the brain is stress and anxiety management. It also plays an essential role in depression. If nerve cells have to be newly formed, this mechanism also has something to do with the endocannabinoid system. Through the influence on the reward system, which is associated with the dependence on drugs, desire for sweets or even gambling addiction, the performance, learning ability and also the memory is influenced.