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What is the Endocannabinoid System and What is its Function Within the Human Body?

Whilst some individuals take cannabis to enjoy a high, increasing amounts of people are trying cannabis (and CBD in particular) for its therapeutic and medicinal benefits.

What you may not know is that those feelings of euphoria (or in the case of CBD, welcome relief from troublesome symptoms) are only made possible by one of our body’s most important biological regulatory structures.

This structure is known as the endocannabinoid system. This system contains an array of receptors that are capable of interacting with chemical compounds such as THC and CBD.

However, it’s function isn’t just to help us enjoy the beneficial effects of different cannabis-derived chemical compounds.

It serves a much higher purpose; homeostasis.

Homeostasis: Maintaining the Body’s Equilibrium

Before delving into the inner-workings of the endocannabinoid system, it’s useful to explain in a little more depth the importance of homeostasis in the context of our daily biological routine.

Described by many as the “Goldilocks Zone”, homeostasis is the biological process of maintaining just the right conditions for our cells to perform at optimum levels.

A good way to visualize homeostasis is by thinking of your body as a set of old fashioned weighing scales. With an equal amount of ongoing biological processes on each side.

To perform cellular-level processes optimally, your body must have the scales level or at equilibrium, with one side weighing exactly the same as the other.

If one set of biological processes takes up more of the body’s operating power (becoming heavier on our hypothetical scales), then our delicate cells begin to lose their ability to operate at their maximum potential.

Our body has a very narrow optimum range, and therefore homeostasis is an everlasting biological balancing act. Our endocannabinoid system is vital in our body’s fight to maintain balance.

It manages to achieve this outcome by sending chemical messages in reaction to stimuli.

For example, when we are too hot, our body releases sweat to help us cool back down. Or when our blood sugar is high, insulin is released to bring those levels back to normal. All of these reactions are part of the body’s goal of achieving homeostasis.

What Are the Key Components of the Endocannabinoid System (ECS)?

Due to the it’s pivotal role in homeostasis, the ECS evolved millions of years ago and is present today not just in humans, but in all vertebrate species.

There are three principal components that make up the overall system which are as follows:

  • Cannabinoid Receptors – These are located on the surface of our cells
  • Endocannabinoids – These are the small molecules that activate the cannabinoid receptors
  • Metabolic enzymes – These enzymes are used to break down the endocannabinoids after they’ve performed their function.

Firstly, let’s begin with the role of the cannabinoid receptors within the ECS.

Cannabinoid Receptors

Cannabinoid receptors are best described as “listening devices” attached atop of our cells.

They are constantly monitoring conditions outside of the cell and transmitting that information back through to the cell, kick-starting appropriate cellular responses to specific stimuli.

There are multiple different cannabinoid receptors, but the most studied and understood receptors are known as CB1 and CB2.

CB1

These receptors are found in the brain and nervous system.

They were discovered by researchers looking at the psychoactive effects of THC, and it’s these receptors that react with THC to give users a “high” sensation.

Although their presence in humans was not confirmed until the late 80s and early 90s, their importance has since been uncovered.

They make up over 50% of the brains cannabinoid receptors, and they outnumber all other cannabinoid receptors combined.

When activated, CB1 receptors reduce the activity of key processes happening within a cell. They do so by flooding neurons (which send messages around the brain and nervous system) with calcium ions, preventing them from firing.

Activating CB1 receptors can have many different effects and biological reactions depending upon where the specific cell is located.

CB2

CB2 receptors are primarily found outside of the central nervous system, primarily in the immune system. They have been found to be only 44% identical to CB1 receptors, yet they still perform the same overall cellular purpose.

The main discrepancies are the different type of cells they’re located within and differences in the chemicals required to activate them.

Since CB2 receptors are mainly found in the immune system, this means their activation reduces the activity of cells within this structure, specifically B cells.

B cells are responsible for recognizing chemical markers of injury or illness. Once recognized, they activate T cells (“soldier” or “doctor” cells) to either fight or treat the infected area.

To activate T cells, B cells release chemical messengers known as chemokines. When activated, CB2 receptors inhibit their ability to produce them, and raises the threshold required for T cells to be released.

Endocannabinoids

Put simply, endocannabinoids are the molecules that bind to and subsequently activate cannabinoid receptors such as CB1 and CB2.

These molecules are produced and released by the body, rather than introduced, as is the case with CBD or THC.

Unusually for biological molecules, they’re synthesized on demand, which means they are created and used exactly when they are needed, rather than stored for later use.

One again, there are two main players; anandamide and 2-AG.

Anandamide

Anandamide was the first endocannabinoid to be discovered. This molecule is a partial activator (agonist) for both CB1 and CB2 receptors.

However, it is a much better agonist of CB1 than it is of CB2.

However, even when successfully bound, anandamide’s activation rates max out at roughly 40% of 2-AG’s comparative activation rates.

2-AG

2-AG is another important endocannabinoid that was discovered not long after anandamide.

As highlighted, 2-AG is much more potent when it comes to activating cannabinoid receptors. In fact, 2-AG is a full agonist of both CB1 and CB2 receptors.

It has also been strongly linked to the “runners high” feeling experienced by many endurance athletes after extreme physical exertion.

Metabolic Enzymes

This third component of the ECS is made up of the enzymes that break down the endocannabinoids once they’ve been used.

The two main enzymes utilized are FAAH and MAGL. FAAH concerns itself with breaking down anandamide, whilst MAGL focuses on taking apart 2-AG.

The main function of the enzymes is to ensure that endocannabinoids are activated and then destroyed before they have been used for too long.

It’s this exact process that distinguishes endocannabinoids from the majority of molecular signals used within the body. For example, hormonal chemical messengers can be utilized for much longer and are stored for later use after completion.

How Do the Components of the ECS Work Together?

The three major components of the ECS described above are found in nearly every major structure and system within the human body.

When certain stimuli knock the body outside of its natural equilibrium (one of the sides becoming heavier or lighter in our weight scales analogy), these three elements are all called into action to redress the balance (homeostasis).

What’s interesting is that the ECS is only called upon in a space- and time-selective manner, to restore the previous physiological state of homeostasis.

With this is mind, let’s look a little closer at what happens in specific areas of the body when the ECS is activated, namely the firing of brain cells in the nervous system and the inflammatory response of the immune system.

ECS Regulation of Brain Cell Firing

The neurons within our brain cells communicate with each other by sending electrochemical signals to each other. They are constantly “listening” to interconnected neurons to ascertain whether to fire its own signal or not.  

However, just like with almost all systems in the body, there is a balance to be had with signals between neurons. Too many signals can overload the neuron and can prove toxic. 

That is, until the ECS kicks in. 

As an arbitrary example, let’s say one “receiving” neuron is listening to two other “sending” neurons. 

One of the “sending” neurons is firing at a normal rate, but the other is overactive and sending far too many signals. The listening neuron, recognizing this is the case, will generate and release endocannabinoids to combat the over-activity.

Once the endocannabinoids have made it to the “noisy” neuron, they bind to the CB1 receptors. As already explained, once the CB1 receptor is activated it then releases calcium ions to reduce the firing to normal levels, returning it to homeostasis.  

Fascinatingly, endocannabinoids do something that neuron signals can’t. 

They travel backwards. 

In our neural networks, signals are only sent one way from a “sending” neuron to a “receiving” neuron that listens and then acts on those signals. 

However, endocannabinoids give neurons the option to regulate the amount of signals they receive by sending them back up the chain to overactive “sender” neurons. This is why endocannabinoids are known as “retrograde signals”. 

Whilst it’s crucial to regulate biological processes in the brain, every one of our systems needs careful regulation to maintain overall homeostasis. Whether that’s the endocrine or the renal system, they all require the ECS to jump in from time to time to maintain the balance. 

The ECS is also activated in the immune system when injury or illness strikes. Hence, let’s review the role of the ECS in the inflammation process during an immune response. 

ECS Regulation of Inflammation

Inflammation is part of the immune system’s response to infection or physical injury.

During this process, pathogens (germs) and damaged tissue are removed. When the body inflames an infected area, it allows the immune cells to move in to remove what’s necessary to allow the body to return to its previous harmonious state.

However, problems arise when the process of inflammation lasts longer than required or spreads from the initial site requiring a response.

Chronic inflammation and auto-immune disease are both classic examples of when the immune system get activated improperly, leading to persistent inflammation or healthy cells coming under attack from our own immune system.

There has been some initial research to suggest that by tweaking the ECS, the effects of inflammatory diseases can be lessened or eradicated completely, since endocannabinoids are so instrumental in the regulation of immune responses.

This makes sense when you consider the role of the ECS during the process of an immune response triggered by a bacterial infection.

To begin with, immune cells detect the presence of the infection and send out pro-inflammatory signals, alerting more immune cells to come and help deal with the infection.

Whilst endocannabinoids are also generated to signal for more immune cells to respond, crucially, they also regulate that response so that it isn’t excessive.

The pivotal ECS regulation of the immune system, allows the usual immune response to take place, whilst ensuring that it comes to a stop once the necessary restorative work has been completed.

This prevents excessive inflammation, and allows the cells within the infected area to return to a state of homeostasis.

How Do Plant-Derived Cannabinoids Interact with The ECS?

The reason that cannabis-derived cannabinoids (known as phytocannabinoids) such as THC or CBD have psychoactive or healing effects on the body is because of their interaction with the ECS.

For instance, THC gives you a “high” because it activates the CB1 receptor within the brain, much like the endocannabinoid anandamide does.

But if anandamide activates CB1 receptors in the brain naturally, then why aren’t constantly in a state of euphoria?

First and foremost, it’s because THC doesn’t interact with the receptors in the same fashion as anandamide. Moreover, the metabolic enzymes that break down our endocannabinoids don’t work on THC, so it stays in our system for a much longer period of time.

You should also note that molecules like cannabinoids rarely interact with just one or two receptor types.

Take CBD for example, it doesn’t just influence cannabinoid receptors in the brain, it interacts with opioid and dopamine receptors too.

But it doesn’t stop there.
CBD can have an effect on the number of endocannabinoids present in the brain (known as “endocannabinoid tone”).

Since CBD inhibits the FAAH enzyme, anandamide levels increase, because there’s no enzyme available to break it down.

This biological phenomenon has been used to explain the success stories of patients using CBD to treat anxiety disorders. Although clinical trials are still ongoing, it’s thought that CBD’s ability to increase the endocannabinoid tone of the brain is behind those early successes.

Therefore, whilst pyhtocannabinoids do activate CB1 and CB2 receptors, it’s important to remember that they also influence the behavior of many other receptors and have an impact on overall endocannabinoid levels, creating more distinct effects on the body.

Recap – The Endocannabinoid System (ECS)

The ECS is made up of three core components, cannabinoid receptors, endocannabinoid molecules, and their metabolic enzymes.

It plays a crucial role in regulating our body’s systems and maintaining the physiological equilibrium known as homeostasis.

Since the ECS plays such a pivotal role in maintaining balance within our bodies, it is used sparingly, only called into action in specific areas experiencing specific circumstances. Once homeostasis is restored, the ECS lays dormant, waiting for its next task.

Whilst it’s true that the ECS can be activated by consuming phytocannabinoids such as CBD, that does not mean that everything within the body will suddenly become perfectly balanced.

Just like any other complex biological system, things can go wrong with the ECS.

If the body endures a state of prolonged absence from homeostasis, it can lose its ability to regulate its own space- and time-selective mandate, and begins interfering with cells that do not require its attention.

When this happens, unfortunately, the ECS begins to aid diseases rather than help to fight them off.

So before you start taking CBD, you must know ahead of time that it’s not a cure-all drug. Our biological make-up is incredibly complex, and thus CBD products interact with everyone differently.

By gaining a deeper understanding of the ECS (and its role in maintaining homeostasis on a cellular level), you can be more appreciative of its efforts, and understand how cannabis-derived therapies help to improve its overall function.

The presence and importance of the ECS in so many of our critical biological systems such as the nervous and immune systems, helps to explain why such a wide variety of ailments have positive responses to cannabis-based treatments.

References

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