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The Endocannabinoid System

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Humans have practiced herbal medicine for thousands of years and the human endocannabinoid systems are evolutionary proof of this. Everyone, whether we enjoy cannabis or not, has an active endocannabinoid system (ECS). And it’s hugely beneficial in keeping our biology in balance.

The ECS is present in both our brains and bodies. It’s the reason that cannabis has several positive yet varying effects. As well as why cannabis assists with anxiety and depression, to immunity and epileptic seizures.

The discovery of the relationship between cannabis and the ECS is still relatively new, much-needed scientific studies are still required to further our understanding. Here‘s what scientists know about the endocannabinoid system.

What is the endocannabinoid system?

“Endo-” is abbreviated from “endogenous.” Which refers to a system that originates within an organism. “Cannabinoid” refers to the plant in which these compounds were discovered: Cannabis.

The ECS is made up of receptors which are located throughout our brains and bodies. It’s involved in the maintenance of several important physiological processes. All of these factors contribute to our health and happiness.

Did you know that the endocannabinoid system isn’t unique to humans? Vertebrates are theorised[1] to share this complex cell-signaling system. This is why cannabidiol oil has grown in popularity for pets in recent years, such as CBD oil for dogs.

When was the endocannabinoid system discovered?

Unfortunately, our knowledge of the ECS in humans has been limited. Mostly by the stereotypes associated with cannabis in politics. It’s still difficult to study the ECS due to legal restrictions in several countries, including Australia.

Tetrahydrocannabinol (THC) was first discovered in the 1960s and the ECS in the late 1980s[2]. The first cannabinoid produced by the ECS, however, was only isolated in the 1990s.

Having discovered cannabinoids recently, we still have much to learn about the ECS itself. We haven’t yet determined how it works entirely. However, scientists have discovered key insights into why the ECS might be medically significant.

What is the endocannabinoid system’s function?

The primary function of the human endocannabinoid system is to maintain homeostasis[3]. This describes the state of balance between your internal physiological systems. The ECS is responsible for regulation of the following body functions:

  • Appetite, digestion and metabolism

  • Bone health and growth

  • Cardiovascular function

  • Chronic pain management

  • Immune and inflammatory responses

  • Liver function

  • Memory and learning

  • Mood regulation

  • Motor control and muscle development

  • Reproductive systems and fertility

  • Sleep

  • Skin, tissue and nerve functions

  • Stress

The ECS responds to changes in our internal environment, which keeps these functions operating in unison. When homeostasis is disrupted, the ECS activates the appropriate bodily response. For example, when white blood cells are being sent to an infected area of the body.

model of a human body

Once the appropriate action has been taken, balance must be restored by “deactivating” such responses. This is regulated by our Endocannabinoid System as well.

To understand how all this works, you need to understand the interactions between the components of the ECS. These are the cannabinoid receptors, enzymes, and cannabinoids.

What are cannabinoids?

Simply put, cannabinoids are chemical constituents of the cannabis plant. Endogenous, or endocannabinoids, are chemically identical to those found in cannabis. These are called phytocannabinoids, meaning they are synthesized in plants.

Cannabinoids are often confused with terpenes, which are also phytochemicals. These are responsible for the unique scent of each of the different strains of cannabis. Terpene-rich oils are secreted by mature cannabis plants.

Although terpenes are also found in other fruits and vegetables and like cannabinoids, they also have associated health benefits.

The function of cannabinoids is to act as neurotransmitters and bind to receptors. This affects the chemical signals received by the nervous system. Which in turn, affects how information is processed by cells throughout our bodies.

There are two main endogenous cannabinoids[4] - those produced inside our bodies:

  • Arachidonoyl ethanolamine (also known as anandamide, or AEA) is associated with appetite regulation as well as motivation and pleasure.

  • 2-arachidonoylglycerol (known as 2-AG) is linked to multiple physiological processes such as cognition, energy and pain.

What are cannabinoid receptors?

person doing yoga

Our body has many receptors. These transport chemical signals between our bodies and brains. Endocannabinoid receptors’ shape compliments both endo- and phytocannabinoids as both have the same structure.

Our cannabinoid receptors are therefore responsible for transporting cannabinoids to areas where they are needed. However, these receptors also identify areas of imbalance. Subsequently stimulating the production of our own endocannabinoids to attend to the imbalance.

What is the function of the CB1 & CB2 receptors?

The two main types of cannabinoid receptors in the human body are the CB1 and CB2 receptors. CB1 receptors are primarily located in the central nervous system - in the brain and spinal cord. However, they are also located in areas of our peripheral nervous systems[5], including:

  • Reproductive organs and gonads

  • Peripheral neurons

  • Retinas

  • Fatty tissues

  • Colons

  • Adrenal glands

  • Hearts

  • Lungs

CB2 receptors are predominantly associated with the immune system function. These are also located in the central and peripheral nervous systems. However, unlike CB1 receptors, CB2 receptors don’t seem to cause psychoactive effects[6].

The CB1 receptor is activated by the 2-AG cannabinoid while the CB2 receptor is compatible with both 2-AG and anandamide. Endocannabinoids can bind to either of these receptors. Different effects are experienced depending on the following:

  • The therapeutic effects of different cannabinoids

  • Which receptors are targeted

  • Where the targeted receptors are located in the body

What are endocannabinoid enzymes?

Enzymes present in the body perform an important part in synthesising chemical reactions. These reactions allow your body to perform tasks such as digesting food, building muscle and breaking down toxins. Enzymes also break down neurotransmitters that are no longer needed.

The two major enzymes involved in breaking down endocannabinoids are:

  • Fatty acid amide hydrolase (which break down AEA)

  • Monoacylglycerol acid lipase (which break down 2-AG)

How do CBD & THC affect the endocannabinoid system?

The most famous phytocannabinoids are Tetrahydrocannabinol (THC) and Cannabidiol (CBD). However, there are many others originating in cannabis.

As previously stated, phytocannabinoids are readily received by the ECS because they’re chemically identical to our endocannabinoids. Which explains why cannabis alone doesn’t trigger an allergic response.

These and other plant-based cannabinoids are severely understudied. However, promising results have emerged from what limited research has been conducted.

The Endocannabinoid System & CBD

Medicinal cannabis is still a controversial topic for most governments. Therefore, there have been more studies conducted into Cannabidiol. Which has become hugely popular for its lack of psychoactive properties.

CBD was introduced to the medical industry as an anti-seizure medication for Epilepsy in children. Since then, it’s been investigated as a treatment option for a range of conditions.

Cannabidiol doesn’t bind to CB1 and CB2 receptors in the same way as other cannabinoids. Scientists are still trying to understand why this is. Some believe that CBD prevents other cannabinoids from being broken down as quickly. Others think that a CBD-specific receptor hasn’t been discovered yet.

Learn more about the benefits of CBD.

The endocannabinoid system & THC

THC and the brain

There are pervasive and harmful stereotypes still associated with THC today. The “high” feeling produced by this cannabinoid doesn’t sit well with everyone. It can even cause intense physical and emotional discomfort in high doses.

More scientific research is needed to explain why some people respond negatively to THC when others don’t. THC binds to both CB1 and CB2 receptors. This is why THC oil can deliver such a wide range of mental and physical benefits. A few specially authorised studies on THC show potential for managing nausea, insomnia and pain.

Learn more about THC’s therapeutic uses.

What is Endocannabinoid Deficiency?

Not all medical professionals agree on the topic of Endocannabinoid Deficiency Syndrome. Also known as Clinical Endocannabinoid Deficiency (CEDC), the theorised illness is heavily debated. Some medical professionals believe it plays a role with seemingly “untreatable” ailments.

This ten-year study[7] collected data from patients with irritable bowel syndrome, fibromyalgia and migraine headaches. It was noted that these individuals had lower levels of endocannabinoids AEA and 2-AG.

Therefore, scientists theorised the following:

  1. The presence of cannabinoid receptors "endocannabinoids" in the human body help maintain balance.

  2. These compounds regulate bodily functions which maintain homeostasis. As such, a significant absence of endocannabinoids may cause these mysterious maladies.

The jury is still out with regards to the validity of CEDC. In order to prove a definitive correlation, however, much more medical interest is required.

The human endocannabinoid system in summary

The human endocannabinoid system is not limited to Homo sapiens. The ECS is shrouded in medical mystery, thanks to years of criminalisation of the humble cannabis plant. There are many strides to be made in terms of understanding this system in its entirety.

However, there is more than enough evidence to warrant further research on the topic. What we do know is that the ECS is responsible for the maintenance of homeostasis - our body's internal regulatory structure. The ECS consists of three main components: endogenous cannabinoids, cannabinoid receptors, and specialised enzymes.

These work together to monitor changes in the body. They then organise the appropriate physiological response, and return the body to “normal” thereafter.

It seems we have a lot to thank our endocannabinoid systems for, even without a full understanding. As more governments wake up to the medical potential of cannabis compounds, we can only speculate on the possible insights awaiting us.

Jason Lu | BudHerd

Jason Lu | BudHerd

Jason is one of the lead editors and founder of BudHerd. He spends his days writing, designing, developing and researching all things cannabis. Jason is passionate about destigmatising and educating Australians on the therapeutic and recreational values of cannabis.
  1. Silver RJ. The Endocannabinoid System of Animals. Animals (Basel). 2019;9(9):686. Published 2019 Sep 16. doi:10.3390/ani9090686

  2. Nazarenus, Christine. The Discovery of the Endocannabinoid System. 2019. https://connect.springerpub.com/content/book/978-0-8261-3573-5/chapter/ch03

  3. Britannica, The Editors of Encyclopaedia. "Homeostasis". Encyclopedia Britannica, 27 May. 2020, https://www.britannica.com/science/homeostasis. Accessed 1 June 2021.

  4. Basavarajappa BS. Critical enzymes involved in endocannabinoid metabolism. Protein Pept Lett. 2007;14(3):237-246. doi:10.2174/092986607780090829

  5. Reggio PH. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr Med Chem. 2010;17(14):1468-1486. doi:10.2174/092986710790980005

  6. P. Kumar, Z.-H. Song. Handbook of Cannabis and Related Pathologies. 2017. https://doi.org/10.1016/B978-0-12-800756-3.00071-5.

  7. Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165. Published 2016 Jul 1. doi:10.1089/can.2016.0009

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