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The endocannabinoid system (ECS) is a regulatory system found in all vertebrate species including humans. This system, and the natural cannabinoids the body produces that interact with the ECS, ensure homeostasis is maintained ( Cottone 2013 ). This means it sends feedback signals to cells to ensure their function is balanced and not overactive or stagnant. Nature , a high-profile nature-based research journal, published cannabis studies with THC in 1988 that led to the discovery of this system ( Marzo 2004 ). The cannabinoids found in the cannabis plant interact with ECS receptors in our bodies, causing their characteristic effects.


The ECS is controlled by two types of cell receptors, CB1 and CB2. These receptors are found on the surface of cells throughout the body, and the highest concentration of this type is found in the cells of the brain and nervous system. CB1 is mostly found in the brain and spinal cord, while CB2 is mostly found in cells associated with the immune system ( Pagotto 2006 ). The body naturally produces two cannabinoids, and they act as signaling molecules that bind to these receptors to perform their function. These naturally produced (endogenous) molecules have been identified as anandamide and 2-AG. Once they have performed their function, they are broken down by enzymes. The ECS in our body, made up of these receptors, naturally produces these cannabinoids and enzymes which help regulate a number of systems in our body. These systems include, among other things, pain, appetite and reproduction.

The high concentration of CB1 in the brain and nervous system is due to its close association with neurotransmitter release and regulation ( Marzo 1998 ). High concentrations of these receptors are found at the synapses between neurons. Neurotransmitters are chemical substances in the body, such as dopamine and serotonin, that act as signals between neurons. When you feel pain, the neurons release neurotransmitters from neuron to neuron through synapses to communicate to the brain that something is painful. If these neurons do not function properly and repeatedly send signals, the pain will feel unbearable. This is where ECS comes into play. Endocannabinoids are able to calm overactive neurons and neutralize them back to their original state of function. This function also happens in reverse. Neuron cells that are inactive can be influenced by the ECS to become active ( Sulak 2018 ).

A good example is what happens in the gastrointestinal tract or in the cardiovascular system when the cells do not function normally. Endocannabinoid levels rise in the brain when a person experiences a stressful event or is reminded of an unpleasant memory. The ECS protects cells from damage that can occur due to overactivity from stressors and likewise from inactivity that can also cause damage to the body.


The ECS is also activated in brain functions related to seizures, when the cells in the brain do not communicate and function normally ( Marzo 2004 ). The FDA approved Epidiolex for the treatment of seizures in pediatric patients. The active ingredient in that medication is CBD, which interacts with the ECS to regulate brain signaling and reduce the occurrence of seizures. The ECS plays a major role in the regulation of this communication in the brain, and drugs to alleviate these problems therefore try to affect the ECS. It also plays a role in the endocrine system, regulating the release and uptake of hormones. The pituitary gland, which is directly linked to the brain, secretes hormones throughout the body to signal everything from hunger to the "fight-or-flight" response, and has many endocannabinoid receptors ( Pagotto 2006 ). The list of functions in the body associated with the ECS is extremely long, but it is true in all cases that its purpose is to ensure that the cells function normally in homeostasis.


Cannabis and its cannabinoids have been used for centuries to interact with the complex system in our bodies. The reason we know about the ECS is actually because cannabis has been widely used throughout history and researchers wanted to know more about how it works in our bodies ( Marzo 2004 ). Like the endogenous cannabinoids already present in our bodies, THC and CBD are able to interact with the ECS receptors to achieve the desired effects. The reason why cannabinoids are used in the pharmaceutical industry is due to the fact that we have receptors for these molecules all over our body. THC's binding CB1 receptors is strong. Since the concentration of CB1 in the brain is so high, you achieve the psychoactive effects that THC is known for. The reason this psychoactivity does not last forever is that we have in our bodies the enzymes necessary to break down cannabinoids. CBD also interacts with these receptors, although studies have shown that it can actually block CB1 receptors and decrease the unwanted or psychoactive effects of THC ( McPartland 2014 ). Cannabis' well-known effect on appetite may also be linked to the presence of ECS receptors in the gastrointestinal tract and pituitary gland.


The endocannabinoid system is very complex and maintains our cells and associated systems. Maintaining a balance in homeostasis is essential for survival. Because the ECS is so widespread in the body and performs regulatory functions, it is effective to target prescription drugs built around cannabinoids such as Epidolex and others approved by the FDA against this particular system. There is a lot of ongoing research into the exact functions of cannabinoids and how they interact with receptors as well as their journey around the body. You would like to obtain that knowledge with a view to developing medicines. Of the top 150 drugs in the United States, 118 of them are derived from plants (Roberson 2008 ). With over 80 unique cannabinoids, cannabis has enormous potential for a wide range of interactions with the ECS, and researchers are working hard to find out exactly how they work and whether they can serve as components of medicine in the future.


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