by: josh alb
Humans have a sense of difference with the world and rightly so because we are a unique species. Homo sapiens at one point were deeply connected to nature. Over the past few millennia that has fundamentally changed. People forget that they are still related to all of life around them. There are similarities humans share with other species such as a similar morphology to chimpanzees. Something that we do share with all mammals, and more importantly with all species, is the endocannabinoid system.
What is the Endocannabinoid System?
A system of receptors throughout the body
The endocannabinoid system is simply a system of endogenous receptors that are located around the central nervous system and immune tissues. This system was discovered recently in 1992 by Raphael Mechoulam. The system is comprised of two known endogenous protein receptors dubbed as cannabinoid (CB for short) receptors. The first is known as the CB1 receptor. It is located in regions parallel to the central nervous system such as the brain, liver, and reproductive organs. The second is known as the CB2 receptor, which is located on immune tissues. There are several other receptors that are hypothesized to be cannabinoid receptors such as GCPR55, but more studies need to be done in order to conclude this.
Image of the CB1 receptor with the cannabinoid tetrahydrocannabinol (THC) in complex.
Photo from via Why Not THC Instagram. Follow for more.
Where is the ECS located?
Quite literally everywhere
The Endocannabinoid System is located all throughout the body. The system runs parallel to the central nervous system where the CB1 receptors are located. It is also located on immune tissues and peripheral organs which is where CB2 receptors are present. This can be better illustrated in the diagram below.
How does the Endocannabinoid System work?
Similar to a driving a car, put it in drive, neutral, or reverse.
When any drug is ingested into the body it can work in one of three different ways. These are referred to as agonist, inverse agonist, and antagonist. Their various functions can be compared to driving a car. Similar to how a car has the functions of drive, neutral, or reverse, so do any molecules’ ability to bind to an active site of a protein. When an agonist, like THC, binds to the receptor is produces specific effects that “turn the receptor on” and “puts the car in drive”. When an inverse agonist, like Rimonabant, binds to the receptor it produces an effect opposite of the agonist, effectively “turning the receptor off” and “puts the car in reverse”. Agonist binding molecules, such as CBD, bind to the receptor and cause it to inhibit any other molecule from binding or interacting with it. This can be thought of “putting the car in neutral”. Cannabinoids will bind to the receptor, each to a specific way, to activate the system and produce specific effects.
The gif above illustrates the comparison between agonist and antagonist interaction. The blue ribbons represent an agonist-binding-cannabinoid-CB1-complex. The pink ribbons represent an antagonist-binding-cannabinoid-CB1-complex. When superimposed the differences are clear as to how each molecule binds to the same site. Each cannabinoid produces different affects based off of the way the the complex of the CB1 receptor undergoes.
Why is the Endocannabinoid System important?
It helps keep you balanced.
This system of endogenous receptors plays a key role in homeostasis. It plays a role in managing everything from mood, appetite, and sleep. Due to these factors it is believed that cannabinoids and the endocannabinoid system play a key role in our circadian rhythm. The endocannabinoid system has also shown a key role in pain management. These findings have supported a number of different movements around the idea of cannabis and cannabinoids being looked into as an alternative from pharmaceutical medication.
Cannabinoids play a balancing act in the body by turning on and off the production of different endogenous molecules when ingested. For example, when ingesting THC you can have the release of serotonin causing a euphoric feeling. CBD, when ingested, has the ability to inhibit the production of adenosine, the key molecule that induces fatigue. These variety of effects happen due to the different ways each one of these small molecules can interact with the body.
Endogenous cannabinoids have been heavily investigated because of this. Researchers have come to conclude that molecules like anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a key role in bodily function. Research shows how anandamide is responsible for assisting in appetite and energy. 2-AG has been shown to play a major role in brain function and protecting the brain from traumatic injuries.
Balance act between endocannabinoids anandamide and 2-AG. Photo from How Endocannabinoids Limit Stress
Overall the Endocannabinoid System plays a major role in taking care of the human body. Understanding it can help one make wiser decisions when consuming any substance that could interact with it. Hopefully this article has shed some light on what the endocannabinoid system is and how it works.