What is the Endocannabinoid System?

Just like in the case of the opioid system reacting to different opioids (codeine, morphine), us humans have a unique receptor system for “cannabinoids”.

The endocannabinoid system (ECS) was first discovered in the late 80’s early 90’s, and there is still a lot that remains unknown about this system today. The ECS contains a plethora of cannabinoid receptors and influences the activity of many other organs and systems within our body. 

Phytocannabinoids of the cannabis plant work in a similar way to our body’s naturally produced endocannabinoids.

To better understand the endocannabinoid system, it’s helpful to know about one of the most fundamental concepts in biology: homeostasis. Homeostasis is the idea that most biological systems within the body are actively regulated to maintain conditions within a narrow range.

For example, our bodies do not want its temperature to be too cold or too hot, its blood sugar levels too low or too high, and so on. For our cells to maintain optimum performance, conditions must be just right. The endocannabinoid system is a vital and exquisite molecular system that helps us maintain this homeostasis. Or what some might call, “the Goldilocks zone”.

The endocannabinoid system plays a crucial role in our nervous system, and regulates many physiological processes, including: response to pain, appetite, digestion, sleep, mood, inflammation, and memory.

The endocannabinoid system also impacts seizure thresholds (i.e. in epilepsy), coordination, immune system response, sensory integration (balance, touch, sense of space), heart function, fertility, bone physiology, neural development, the central stress response system (HPAA), and eye pressure.

The Three Main Components of The ECS:

  • Cannabinoid Receptors – found on the surface of cells
  • Endocannabinoids – small molecules that activate cannabinoid receptors
  • Metabolic Enzymes – break down endocannabinoids after they are used

Cannabinoid Receptors

Our brain, among other organs, contain naturally occurring cannabinoid receptors and the chemicals that bind to them. This array of receptors is known as the human endocannabinoid system (ECS) and its role is to maintain our body’s ability to function in homeostasis by influencing the other systems of the body.

Cannabinoid receptors sit on the surface of cells and “listen” to conditions outside the cell. They communicate information about changing conditions to the inside of the cell, activating the appropriate cellular response.

There are two major cannabinoid receptors:

  • CB1 – these receptors are most abundant in the central nervous system, including on neurons in the brain.
  • CB2 – these receptors are most abundant outside of the nervous system, including cells of the immune system.

Although more local to certain systems, both CB1 and CB2 receptors can be found throughout the entire body.

Endocannabinoids (& Phytocannabinoids)

“Endo” means “within”, as within the body. This means, us humans produce our own cannabinoids. These cannabinoids are referred to as “endocannabinoids”. Endocannabinoids act on, or stimulate our cannabinoid receptors. They act in a similar way as phytocannabinoids (plant cannabinoids), which also bind to our receptors. 

There are two major endocannabinoids:

  • Anandamide – derived from the sanskrit word “ananda”, which means “bliss”, anandamide is sometimes referred to as “the bliss molecule”. More scientifically known as N-arachidonoylethanolamine (AEA), this fatty acid neurotransmitter is believed to have an impact on working memory and early stage embryo development.
  • 2-AG – 2-ArachidonoylGlycerol (2-AG) was previously a known chemical compound, but then scientists became aware of its affinity toward cannabinoid receptors. It is present at high levels in the central nervous system and has been identified in maternal bovine as well as human milk.

Both of these endocannabinoids are made from fat-like molecules within cell membranes, and are synthesized “on-demand”. Meaning, they are made and used exactly when they are needed, rather than packaged and stored for later use like many other biological molecules.

Plant cannabinoids are referred to as “phytocannabinoids”. These are unique constituents of the cannabis plant. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most well-known constituents, but there are a plethora of other cannabinoids being studied currently.

As our knowledge of the human endocannabinoid system progresses, so will our understanding of how phytocannabinoids, THC, CBD and other cannabinoids work. This knowledge will lead to better medicines.

Metabolic Enzymes

The third and final piece of the endocannabinoid triad is the metabolic enzyme. This enzyme’s job is to quickly destroy endocannabinoids within the ECS once they are used. 

There are two major enzymes:

  • FAAH – breaks down anandamide
  • MAGL – breaks down 2-AG

These enzymes make sure that endocannabinoids are used when they’re needed, but not for longer than necessary.

This specific process differentiates endocannabinoids from other molecular signals in the body, such as hormones or classical neurotransmitters, which can persist for longer periods of time, or get packaged and stored for later use.

The ECS Triad

These three key components of the human endocannabinoid system can be found throughout the entire body. When something brings a cell out of homeostasis, these three are often called upon to bring things back.

The endocannabinoid system is often engaged only when and where it’s needed. Research Director at the Institute of Biomolecular Chemistry in Italy, Dr. Vincenzo Di Marzo, explained it this way:

“With the ‘pro-homeostatic action of the ECS’ we mean that this system of chemical signals gets temporarily activated following deviations from cellular homeostasis. When such deviations are non-physiological, the temporarily activated ECS attempts, in a space- and time-selective manner, to restore the previous physiological situation (homeostasis).”

To put it simply, the endocannabinoid system helps to bring things back to biological balance.

Let’s now consider how the endocannabinoid system helps to maintain balance in two areas: brain cells within the nervous system and inflammatory response within the immune system.

Endocannabinoids & Brain Cells

Brain cells, AKA “neurons”, communicate with one another by sending electrochemical signals. These neurons must listen to one another in order to decide whether they will fire off their own signals. 

Nevertheless, neurons do not like too much input. Just like the rest of the body, they have a specific homeostasis zone. If they for some reason get overloaded by signals, it can be harmful. This is where endocannabinoids come to the rescue.

Consider this hypothetical scenario:

A neuron is listening to two other neurons when one of the two outputting neurons becomes overactive and sends way too many signals to the listening neuron. In reaction to this overload, the listening neuron makes endocannabinoids and transmits them back to the overactive neuron. The endocannabinoids give a signal to the overactive neuron to “quiet down” – bringing things back to homeostasis.

This example shows that endocannabinoids have the ability to travel backward, which is why they are sometimes referred to as “retrograde signals”. Usually, the information flow between neurons is one-directional, from the sender neuron that releases the neurotransmitter signals to the receiver neuron that listens to those signals. Endocannabinoids, however, allow the receiver neurons to regulate how much input they are getting. They do this by transmitting retrograde signals (endocannabinoids) back to the sender neurons.

Now that we’ve seen how endocannabinoids keep the brain in homeostasis, let’s look at how other organs and systems within the body are able to reap the same benefit.

Endocannabinoids & Inflammation

Inflammation is our body’s natural protective reaction that the immune system has when we experience infection or physical damage. The function of inflammation is to eradicate pathogens or damaged tissue. The inflammation (swelling) you see when your body is having an immune response is simply fluid and immune cells moving into the affected area to work things out.

However, it is vital that inflammation is limited to the affected location and does not carry on longer than needed, which can cause problems. People who suffer from chronic inflammation and autoimmune diseases have an immune system that is getting activated inappropriately. When this occurs, their inflammatory response lasts longer than needed, resulting in chronic inflammation, or directing its attacks on healthy cells, which is known as autoimmunity.

Endocannabinoids are able to suppress the immune system’s inflammatory response. Vice President for Research at the University of South Carolina, Professor Prakash Nagarkatti, explained, “Most of our research demonstrates that endocannabinoids are produced upon activation of immune cells and may help regulate the immune response by acting as anti-inflammatory agents. Thus, interventions that manipulate the metabolism or production of endocannabinoids may serve as a novel treatment modality against a wide range of inflammatory diseases.”

Let’s consider a typical immune response that could be triggered by a bacterial infection: 

Initially, immune cells would detect the presence of the bacteria and would release “pro-inflammatory” molecules that communicate to other immune cells to join and fight. These pro-inflammatory molecules also initiate the release of endocannabinoids. The more endocannabinoids present, the better the signal to other immune cells that there is assistance and less need for an excessive inflammatory response. This allows cells, and the body, to return homeostasis more quickly after an immune response.

THC, CBD & The ECS

The main reason that phytocannabinoids (plant cannabinoids) have psychoactive and medicinal effects within our body is largely due to the fact that we have an endocannabinoid system (ECS) that they are able to interact with. To give an example, THC is able to get you high because it activates CB1 receptors within the brain. Our own endocannabinoids (i.e. anandamide) also activate CB1 receptors.

So, if this is the case – you’re probably wondering… Why aren’t we always high?

Here’s why. First off, THC does not interact with our CB1 receptors in the same way as our body’s endocannabinoids. Second, our metabolic enzymes that break down endocannabinoids like anandamide do not work on THC. Therefore, THC lingers around for much longer.

Also, cannabinoids rarely interact with only one receptor type. Often, they interact with many. The plant-based cannabinoid CBD demonstrates this the best, as it interacts with various different receptor types within the brain.

Phytocannabinoids may stimulate the same cannabinoid receptors as endocannabinoids, but they will normally interact with several other receptors at the same time. This interaction will have a distinct effect.

CBD is especially fascinating because it is able to affect our brain’s overall levels of endocannabinoids, referred to as “endocannabinoid tone.” CBD prevents the FAAH enzyme from breaking down anandamide. This means that CBD can grow our anandamide levels by preventing their breakdown. This inhibition of the FAAH enzyme has been shown to be an effective strategy for treating many anxiety disorders.

Summary

The human endocannabinoid system is made up of three main components: cannabinoid receptors, endocannabinoid molecules, and metabolic enzymes. It is a crucial system within the body that helps to maintain overall homeostasis. Due to its critical job in making sure that the body remains in balance, the endocannabinoid system is firmly regulated. The ECS is only deployed exactly where and when it is needed. 

By studying and understanding our biological homeostasis, and how the endocannabinoid system influences this at a cellular level, we can come to appreciate our ECS. We can also see how cannabis-based therapies may assist us in creating a sense of even more balance within the body. 

The existence and vital function of the endocannabinoid system across many systems within the body, makes clear why such a wide variety of diseases and ailments are receptive to cannabis-based therapies.

At Nature’s CBD Box, we understand the transformative properties of CBD on the endocannabinoid system. That’s why we’ve curated a subscription bundle of CBD products for balance of mind and body.

If you’re attracted to the idea of wellness and relief, check out our products today! Let us help you find homeostasis.

References

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  • Gunduz-cinar O, Hill MN, Mcewen BS, Holmes A. Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends Pharmacol Sci. 2013;34(11):637-44. [PDF]
  • Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215. [PDF]
  • Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296(5568):678-82. [PDF]