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The Endocannabinoid System 101: What you need to know

The endocannabinoid system is a relatively newly discovered bodily system. It plays an important role in our overall health and wellness. This is what you need to know about it.
The endocannabinoid system

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A key role in our health and wellness

Since hemp was legalized in the 2018 Farm Bill, the popularity of CBD has skyrocketed. It seems like you can’t go anywhere without hearing about it or seeing it for sale. 

Research shows that CBD seems to be helping people treat and manage a myriad of symptoms from pain and inflammation, to anxiety, stress, and sleep, but how is one compound able to address such a wide range of problems?

The answer lies in the effects of cannabinoids on our bodies’ endocannabinoid system. In this article we’re going to take a closer look at what the endocannabinoid system is, as well as the role it plays in our health and wellness.

What is the endocannabinoid system?

The endocannabinoid system is a vast biochemical signaling network that exists within every mammalian brain and body. Most people have heard of other transmitter systems that keep their body functioning properly, such as the central nervous system or immune system, but the endocannabinoid system is less well-known.

The endocannabinoid system consists of three main components including cannabinoid receptors, endocannabinoids, and metabolic enzymes.

Cannabinoid receptors

Cannabinoid receptors are located throughout the brain and the body and scientists have currently identified two different types. 

CB1 receptors

Our cannabinoid type-1 receptors, or CB1 receptors are primarily concentrated throughout the central nervous system in our brains, but CB1 cannabinoid receptors can also be found in our lungs, gut, liver, kidneys, and skin.

CB2 receptors

Our cannabinoid type-2 receptors are primarily found throughout our bodies, in our peripheral nervous system, immune system, and metabolic tissues, as well as many of our internal organs and skin.

Endogenous cannabinoids

Endogenous cannabinoids, or endocannabinoids (for short), are our body’s own naturally occurring cannabinoids. Like dopamine and serotonin, endocannabinoids are neurotransmitters that are responsible for sending messages around the body between the cannabinoid receptors. However, unlike other neurotransmitters, endocannabinoids travel backwards from the post-synaptic nerve to the pre-synaptic nerve.

The first endogenous cannabinoid that was discovered was named anandamide (AEA) or the bliss chemical (after ananda which is the Sanskrit word for bliss). Shortly after, another endocannabinoid was discovered, named 2-arachidonoylglycerol (2-AG), and this was followed by many more. However, scientists have been finding it difficult to quantify how much of each endocannabinoid our body’s produce because they’re produced on-demand, as and when they’re needed.

Phytocannabinoids (phyto meaning from plants), which are structurally similar to endocannabinoids, are also able to communicate with and activate our cannabinoid receptor sites, which is what allows cannabis to hijack our endocannabinoid systems and why it possesses such great therapeutic potential.

Metabolic enzymes

Metabolic enzymes are responsible for breaking down our bodies’ endogenous cannabinoids after they’ve carried out their function. Fatty acid amide hydrolase (FAAH) enzymes are responsible for breaking down AEA and monoacylglycerol acid lipase typically breaks down 2-AG.

What is the endocannabinoid system

What is the endocannabinoid system’s role?

So, now we know what it is, what does the endocannabinoid system do? In short, the endocannabinoid system is responsible for helping our body to achieve and maintain homeostasis. 

Every function in the human body requires balance in order to perform optimally and the endocannabinoid system (or ECS for short) is essential in regulating most of the body’s vital physiological and cognitive functions.

Endocannabinoids bind to and activate our CB1 or CB2 receptors (or both) in order to trigger a chain-reaction of events which influence a vast number of processes that control pain, sleep, mood, motor control, inflammation, and more.

By traveling backwards and communicating at CB1 and CB2 receptor sites, our endocannabinoids are able to encourage or inhibit the release of other neurotransmitters such as serotonin, dopamine, and glutamate. And it is by regulating the release of these other neurotransmitters that the ECS is able to cast such a wide net of influence over so many areas. 

For example, CB1 receptor regulation is able to exert influence over processes such as pain sensation, appetite, mood, stress response, memory, glucose metabolism, fertility, and sleep. CB2 receptors help to regulate or balance immune function and inflammatory response, among other things.

One team of researchers said that “modulating ECS activity holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders, obesity/metabolic syndrome, cachexia, chemotherapy-induced nausea and vomiting, tissue injury and pain, among others”.

For all intents and purposes, your ECS acts like a network of traffic controllers, attempting to balance out the actions of various other systems in your body, which is why the therapeutic potential of cannabinoid supplementation is thought to be so large.

Endocannabinoid deficiency

Due to the essential roles the endocannabinoid system plays in maintaining the body’s optimal performance, it is thought that many (if not all) serious illnesses or medical conditions are the result of endocannabinoid system deficiency.

Endocannabinoid system deficiency can be a result of your body not producing enough endocannabinoids. But it can also occur if your body isn’t producing enough cannabinoid receptors or is producing too many metabolic enzymes that are recycling your endocannabinoids too quickly. Some medications and foods can also disrupt endocannabinoid signaling.

If you’re experiencing endocannabinoid deficiency, then other systems and processes can easily fall out of balance, manifesting themselves in some form of sickness or symptom. More and more scientists believe that the ECS is far more important than we once thought and may even hold the key in treating previously untreatable conditions such as migraines, IBS, and fibromyalgia.

How does THC interact with the ECS?

THC, or tetrahydrocannabinol, is one of the most abundant and famous of all cannabinoids that can be found in cannabis. It is also the cannabinoid that is responsible for making you feel high when you ingest cannabis.

THC is a cannabinoid receptor agonist, which means it interacts with the endocannabinoid system by directly binding to CB1 and CB2 receptors in your brain and body, which is why it’s able to alleviate pain and nausea and increase appetite.  This binding at CB1 receptor sites is also how it makes you feel intoxicated.

How does CBD interact with the ECS?

Unlike THC, CBD (or cannabidiol) doesn’t bind directly to cannabinoid receptors and therefore doesn’t have the same ability to intoxicate you. The way CBD is able to exert influence appears to be a little more complicated than THC and scientists are still working these details out.

Negative allosteric modulator

Interestingly, CBD has been found to be a negative allosteric modulator of CB1 receptors, which means it has the ability to change the shape of those receptors, resulting in THC not being able to bind to them so well. By acting as a negative allosteric modulator at CB1 sites, CBD is able to block some of THC’s intoxicating effects.

Anandamide reuptake inhibitor

CBD appears to inhibit the breakdown of anandamide and other endocannabinoids, increasing the concentration of endocannabinoids available in our brain and body, elevating our body’s overall endocannabinoid tone. It does this by hitching a ride with Fatty Acid Amide Hydrolase (FAAH) enzymes responsible for recycling AEA in the brain, which prevents these enzymes from fulfilling their main task.

Other modes of action

Their is also research to suggest that CBD interacts with other receptors in the body including:

  • Serotonin 5-HT1A receptors – these receptors help regulate pain, sleep, addiction, appetite, anxiety, and nausea
  • TRPV1 receptors – these receptors are involved in regulating pain, inflammation, and body temperature
  • PPAR-Gamma receptors – these receptors help remove beta-amyloid plaque (this plaque build-up can lead to Alzheimer’s), as well as regulate lipid uptake, insulin sensitivity, and dopamine release
  • Dopamine D2 receptors – these receptors are also targeted by antipsychotic drugs

When was the endocannabinoid system discovered?

I’ve heard that some people are quite skeptical over the existence of the endocannabinoid system and I think it’s understandable that there is a lot of mistrust. I mean, if it’s so important, 1) why didn’t we learn about it at school? And 2) why does it sound so suspiciously like the word cannabis?

And the answer to those (very relevant) questions are:

1. We didn’t learn about the endocannabinoid system at school because it just hasn’t been written into the curriculum yet. Despite being discovered 30 years ago, in the early 1990’s, there’s still so much we don’t know about it

In fact, nurses and doctors aren’t even taught about the endocannabinoid system yet. Apparently there’s just so much to learn already (in order to be a doctor) that no-one has worked out how to squeeze this extra information into the curriculum. That news is pretty shocking when you consider how vital this system could eventually prove to be to overall health.

2. And the reason it sounds so much like the word cannabis and cannabinoids, is because cannabis and cannabinoids were discovered first. Our endocannabinoids are structurally similar to the cannabinoids found in cannabis, with the prefix “endo” describing that these cannabinoids originate within us.

The bottom line

The importance of the endocannabinoid system and the critical role of cannabinoids in our health and wellbeing is finally being recognized and, after nearly a century of cannabis and hemp prohibition, more scientists are now able to study the effects of cannabinoids for research purposes.

There’s already one FDA-approved, CBD-based pharmaceutical drug available in the US called Epidiolex, which is used in the treatment of seizures. But several other CBD and THC-based medications are also going through clinical trials right now, for the treatment of pain, anxiety, sleep, and autism spectrum disorder, amongst other things.

Luckily for us, CBD enjoys an incredibly favorable safety profile (read more in our article about the side effects of CBD), which is one of the reasons that so many people are keen to try it for themselves, despite the lack of human clinical trials.

And in the case of CBD, it looks like the public is way ahead of Big Pharma. People are putting their faith in the therapeutic potential of cannabinoids based on preclinical research and anecdotal evidence and are getting great results. Many CBD users are even ditching pharmaceuticals in favor of cannabinoid supplementation, as a more natural and safe approach to wellness.

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