The Endocannabinoid System

The endocannabinoid system (ECS) is a biological system that is involved in regulating a range of cognitive and physiological processes. It regulates how cannabis affects you, it also regulates your pleasure, pain, memory, mood, appetite, sleep, fertility, pregnancy and pre/post-natal development.

The Endocannabinoid system aims for homeostasis. It likes to keep things ‘in the middle’, working to maintain a stable internal environment even if the external environment is fluctuating.

There are 3 main parts to the Endocannabinoid system.

1. The ‘cannabinoid receptors’ themselves, located on the surface of cells
2. The ‘Endocannabinoid molecules’ that fit into the receptors
3. The ‘metabolic enzymes’ that will actually breakdown the cannabinoids once they have been used

 1. Cannabinoid Receptors

They act as the middle man. Located on the surface of a cell, they receive information from the outside and communicate it to the inside. The information that’s being communicated will make the cell react into taking the appropriate action.

Cannabinoid binding sites are found throughout the central and peripheral nervous system. The two major cannabinoid receptors are called CB1 and CB2. We find the majority of the CB1 receptors are located in the brain and that CB2 receptors are mostly located in the immune system. That being said, we can also find both of these receptors in small amounts throughout the whole body.  It is believed that there are more cannabinoid receptors present in our bodies than any other receptor system!

The CB1 receptor is the site at which the plant cannabinoid called THC interacts, this is what creates that ‘high’ feeling.

Researchers speculate that there could even thought to be a third CB receptor.

 2. Endocannabinoids

The cannabis plant produces phytocannabinoids and humans produce endocannabinoids naturally in their cell’s membrane. (‘endo’ means within, I.e. within the body).

Just like the plant cannabinoids, human endocannabinoids bind to receptor sites.

The human body produces two main endocannabinoids:

-Anandamide and 2-arachidonoylglycerol (2-AG).

They are made within cell membranes from fat-like molecules and are made only when required. They are not made and stored like many of our other biological molecules. Endocannabinoids are on-demand molecules.

The plant cannabinoid called THC and our two human cannabinoids called Anandamide and 2-AG all activate the CB1 and CB2 receptors.

However, please note that the level of potency varies between the human cannabinoids and plant cannabinoids.

 3. Metabolic Enzymes

The last part of the puzzle is the metabolic enzymes that breakdown the endocannabinoids once they have done their job. The two major metabolic enzymes are called FAAH and MAGL.

-FAAH (Fatty acid amide hydrolase) breaks down anandamide.

-MAGL (Monoacylglycerol lipase) breaks down 2-AG.

MAGL and FAAH enzymes breakdown the endocannabinoids as soon as they are not being used.

Other signaling systems in the human body can remain in the system when not in use. However, this is not the case for the endocannabinoids, as soon as they are not needed, they are broken-down.

Note; These MAGL and FAAH enzymes are nowhere near as effective at breaking down phytocannabinods like THC in comparison to our own endocannabinoids.

Conclusion

Now that we understand the three main components of the Endocannabinoid system, we need to understand why humans have it and what it is trying to achieve.

The endocannabinoid system is always looking for homeostasis (happy middle ground). The three main components of the endocannabinoid system can be found throughout the whole body and they play a role in almost every major bodily system.

To put it simply: When a system goes out of balance, the endocannbinoid system can react to bring it back into line.

Endocannabinoids in the brain

Let's look at an example of how endocannabinoids regulate brain cells and keep them in homeostasis.

The human brain has over 100 billion brain cells. These cells are called neurons and communicate with each other by sending electrochemical signals.

Neurons listen to their neighbors’ incoming message (electrochemical signal) and decide if it’s relevant for them to pass on that message.

Problems can arise if neighboring neurons start shouting a message as opposed to talking clearly, they are essentially being too loud and as such the receiving neurons will find it hard to distinguish what the message actually is.

If all the neurons end up shouting a loud message, it can be essentially toxic for the receiving cell because it is unable to comprehend the message…and this is where the beauty of endocannabinoids come in play.

To prevent these neighboring neurons from continuously shouting, the receiving cell produces an endocannbinoid. The endocannabinoid travels back up the neural pathway to bind with a cannabinoid receptor. This is where the endocannabinoid passes on a message for the shouting cell to be quiet. 

The shouting cell gets the message, quietens down and thus homeostasis is reinstated.

This shouting cell is a basic example of how neuron signaling works. Usually signals will strictly travel in one direction, however the endocannabinoids can actually go back down the line and thus are called retrograde signals. Retrograde signals help to regulate the amount of input they are receiving from other cells.  

As we have discussed before, the endocannabinoid system can be found all over the body. The example of the brain cells is but a small fraction of what the endocannabinoid system helps regulate.

So what happens if your endocannabinoid system isn’t functioning properly? Essentially you cannot maintain homeostasis and this is where things can start to go wrong.

Is supplementing with phytocannabinoids a solution? This is exactly what science is trying to figure out!

What happens when we supplement with phytocannabinoids?

Just like our own endocannabinoids, phytocannabinoids can interact with our endocannabinoid system.

For example, when THC is ingested it activates the CB1 receptor and the result is that a person would experience a "high" feeling.

This is only allowed to happen because just like a key and lock, the THC key is the perfect shape for the receptor lock.

The feeling experienced from plant phytocannabinoids will be slightly different in comparison to our human endocannabinoids. It's interesting to note that the metabolic enzymes that usually breakdown endocannabinoids like anandamide, don’t work as effectively on THC and as such the THC cannabinoid will stay in your system much longer.

This is one of the main reasons why a ‘plant’ high lasts much longer as opposed to a high from endocannabinoids.

Interesting fact: Runners high is now believed to be associated with the natural release of your own endocannabinoids!

So, now we know that phytocannabinoids like THC can interact directly with our endocannabinoid receptors, can they interact with other types of receptors too?

Yes, a good example of this is the phytocannabinoid CBD, it can regulate the number of endocannabinoids in our brain without binding to a receptor site.

How does CBD work in our brains?

CBD inhibits the FAAH enzyme. Remember it was the FAAH enzyme that breaks down the endocannabinoid called anandamide.

So, if CBD prevents the FAAH enzyme from breaking down anandamide, supplementing with CBD will mean there is more anandamide readily available for human cells to use. Through phytocannabinoid supplementation we are able to change/increase what’s called the endocannabinoid tone.

If a human is low in the number of endocannabinoids available for signaling. This would mean their endocannabinoid system isn’t functioning correctly.

To resolve this; one solution is to supplement with CBD and additional phytocannabinoids.

The CBD would help naturally boost the number of endocannabinoids available to our system. By increasing the number of endocannabinoids available, we can raise the endocannabinoid tone and thus help us get back to that happy medium of homeostasis.

CBD does not directly bind with cannabinoid receptors, however it can bind directly with other receptor sites.

A final note; supplementing with cannabis will not always be the solution and there is no one size fits all. The endocannabinoid system is tightly regulated and activates when necessary. Like anything, over stimulation can have negative consequences just as much as under stimulation.

Ideally a person shouldn’t need to supplement with anything, because that would indicate they are functioning just as their body intended; in homeostasis. However sometimes we all need a little help.