The Functioning Endocannabinoid System (ECS) | Open Book Extracts

by Justyn Bostic
Endocannabinology and a Healthy You. 

The endocannabinoid system (ECS) is involved in countless aspects of wellbeing. It acts as a sort of all-purpose biological thermostat, automatically correcting physical or emotional imbalances. This means that it has a hand in everything from sleep, to mood, to appetite, to memory, and even immunity. 

Doctors studying endocannabinology – a new field concerned exclusively with the health of the ECS–have recently started developing practices that optimize ECS function. This may seem like a narrow focus, but considering the range of the ECS, it is incredibly important. In order to understand how to support your ECS and enhance your bodily balance, it is helpful to be something of an endocannabinologist yourself. 

This post will cover what the ECS is and how it works, so that you can make informed decisions about your ECS health and the practices that promote it. 

What is the endocannabinoid system (ECS)? 

The ECS is basically a biological messaging network that exists throughout your brain and body. The function of the ECS is to keep your body in a state of equilibrium, or homeostasis. Whenever something is thrown out of balance – your mood, temperature, immune system, etc.– the ECS steps in to restore order. 

It does so with three core components: endocannabinoids, enzymes, and receptors. These elements work in unison to recognize problems, send messages, and translate those communications into restorative action at the cellular level. 

Within this system:

Cannabinoids function as the messengers

Enzymes manufacture and dispatch the messengers when they are needed and destroy them when they are not

Cannabinoid receptors receive and translate the message


Let’s dive deeper into that.

What are Endocannabinoids?  The Messengers

As the name “endocannabinoid” suggests, these transient molecules are cannabinoids that have been endogenously produced by the body. The name also informs us that they are cannabinoids, molecules that are similar to cannabidiol (CBD). 

But what do endocannabinoids do? 

Endocannabinoids act as chemical messengers. They communicate with cellular receptors in the body and effectively tell them what to do. There are two main endocannabinoids, anandamide (AEA) and 2-AG, and two key receptors, CB1 and CB2. What the endocannabinoid “tells” the receptor to do depends on which endocannabinoid has bound to which receptor.

The Two Main Endocannabinoids
Anandamide: The Blissful Endocannabinoid

In certain scientific communities, this endocannabinoid is called N-arachidonoylethanolamine (AEA). However, most people know it as “anandamide,” a name derived from the Sanskrit word “ananda” which means “joy” or “bliss.” It is a fitting moniker. 

In animal studies, anandamide has been observed to produce anti-depressant and anxiolytic (anti-anxiety) effects, and to amplify the hedonic pleasure experienced when eating sweet foods. Beyond the pleasure principle, anandamide has also been found to inhibit the proliferation of breast cancer cells in humans, reduce eye pressure in rats, and reduce sensations of pain in mice. 

2-AG: The Emotional and Cognitive Enhancer 

The other key endocannabinoid that we can produce on-demand is 2-AG (2-Arachidonoylglycerol). 2-AG may not have a fancy name like “anandamide,” but that doesn’t mean it’s not important. In the short time that we’ve known about 2-AG, the endocannabinoid has been found to play a role in many emotional and cognitive functions, as well as energy balance, pain sensation, and neuroinflammation.

When discussing the benefits and effects of endocannabinoids like 2-AG and anandamide, however, it is important to remember that these molecules are only messengers. They are just one part of a long chain of reactions throughout the ECS. They are as responsible for causing biological effects as a symphony conductor is for making music: they create key signals, but not the noise itself.

Enzymes: The Dispatchers

Enzymes are specific types of proteins that help create, destroy, or transform molecules. They are the first responders in the ECS, and start the process by transforming lipids (fats) into specific endocannabinoid ligands (A ligand is any molecule that binds to other molecules). These endocannabinoid ligands will eventually bind to receptors in the ECS, but we’ll get to that later.

Enzymes are crucial to the entire ECS. They turn fat into endocannabinoid messengers that can bind to the receptors and correct imbalances. Without these enzymes, the ECS would be unable to restore balance. However, being able to make corrections is only helpful if there is a way to avoid over-correcting.

Once endocannabinoids have bound to receptors and conveyed their message, new enzymes step in to destroy them. This effectively destroys the messenger and ends the message. In this way, enzymes help endocannabinoids communicate messages on demand. They dispatch messengers when messages are needed, and then eliminate those messengers once the message is received. This effectively solves any overcorrecting issue. 

The Receptors: CB1 & CB2

After endocannabinoids are produced, they are transported to cannabinoid receptors throughout the brain and body. Cannabinoid receptors are a special class of cell membrane receptors that can be found in brain cells, central nervous system cells, and in cells throughout the immune system and other organs.

The two main cannabinoid receptors are CB1 and CB2. CB1 receptors are found predominantly in the central nervous system, in the brain and spinal cord. However, they also exist in many other major organs, such as the heart, lungs, adrenal glands, and reproductive organs. These receptors participate in a wide range of brain functions including, emotional changes, reward perception, and memory

CB2 receptors are more peripheral and can be found mainly in the immune system, where they play an important role in immune response and inflammation. Studies have observed that animals with fewer CB2 receptors experienced exacerbated inflammation. This research suggests that inflammatory diseases like allergies, asthma, and autoimmune problems could be related to poor CB2 function. 

How do Endocannabinoids and Receptors work together?

Yet our body’s inflammatory responses and immune function cannot be boiled down to the number of cannabinoid receptors present. It is also important to consider when receptors are being activated, and by which cannabinoid. 

Anandamide binds primarily with CB1 receptors, while 2-AG is typically coupled with CB2 receptors. However, recent studies suggest that endocannabinoids and receptors can be paired in many different ways. 

For example, 2-AG usually binds with CB2 receptors in immune cells to affect an anti-inflammatory response. But, when anandamide binds with those receptors instead it can trigger a pro-inflammatory response. Inflammation is not always a bad thing. The inflammatory response is our primary defense against infections and other toxins. However, when inflammation lingers and becomes chronic it can cause problematic symptoms.

Different recepter-cannabinoid pairings allow the ECS to act as a multi-purpose balancer. When some bodily function–immune response or mood for example–is not operating optimally, endocannabinoid messengers tell receptors in cells to start powering it up. However, when those things are too high, different combinations of endocannabinoid messengers and receptors can have those same cells lower levels back to normal. 

Biohacking: ECS Maintenance

In an ideal world, our bodies would work exactly as described above. We would float through life in a state of corporeal harmony. Whenever anything knocked us off balance, our ECS would jump into action. Its enzymes would manufacture the right endocannabinoids, and those endocannabinoids would then find and bind to the right receptors, triggering a desirable, corrective response. Order would be restored, and our bodies would exist in perpetual balance. Unfortunately, that’s not really how it works. 

Things like chronic stress, unhealthy diets, and environmental toxins can prevent the ECS from working optimally. In order to support your ECS, many doctors advise regular exercise, stress reduction, and a diet rich in whole foods.  We’ve all heard this advice before, but there has to be more we can do to support our ECS.

Some doctors advocate for a diet specifically designed to supply the omega-3 and omega-6 fatty acids (lipids) you need to create endocannabinoids (ligands). Walnuts, sardines, and salmon are particularly high in omega-3s. As are chia, flax, and hemp seeds — no surprise on the hemp. Dark chocolate also contains compounds that can inhibit the breakdown of endocannabinoids in your body. Finally, a variety of herbs and spices–including tea leaves, echinacea, and turmeric– can help stimulate your CB1 and CB2 receptors.

Calling for Back-Up: Phytocannabinoids 

The diet and lifestyle choices described above are great ways to help your body naturally produce endocannabinoids. However, if creating compounds that activate CB1 and CB2 receptors is the goal, there is a more direct way to accomplish that: supplementing with phytocannabinoids. 

Phytocannabinoids are cannabinoids that come from plants. These stand in contrast to the endocannabinoids which are endogenously produced by your body. Amazingly, many of these phytocannabinoids are so similar to endocannabinoids that your CB1 and CB2 receptors cannot differentiate between them. This means that when you consume phytocannabinoids, you are consuming substances that bind to CB1 and CB2 receptors, just like endocannabinoids do. 

There are hundreds of phytocannabinoids like THC, CBD, CBN, CBV, and more that we are yet to discover. Unfortunately, much of what we know about the ECS has been filtered through the lens of just one. THC. 

As the active ingredient in marijuana, THC has been a locus of scrutiny and stigma for decades. But THC is one of the primary reasons we know what we do about the ECS. Scientists were able to reverse engineer an understanding of the ECS by experimenting with THC. 

In doing so, they discovered that the system they were studying was much bigger than THC, and that other phytocannabinoids could have amazing therapeutic potential. CBN might function to support sleep and inflammation, and CBD may provide relief from stress, anxiety, soreness, and more. 

THC is not your typical phytocannabinoid. It is the only psychoactive major cannabinoid, which has made it highly stigmatized. However, because of the spotlight it has received (positive or negative), it has become the most studied phytocannabinoid by far. The following paragraphs will explain how THC works in the ECS, with the goal of illustrating how other non-psychoactive phytocannabinoids work. 

We are able to isolate various phytocannabinoids and remove THC from CBD supplements. So while THC is helpful in explaining the ECS, it is absolutely not a necessary or requisite part of phytocannabinoid supplementation. 

THC & Anandamide

Each phytocannabinoid interacts with cannabinoid receptors in a slightly different way. For example, THC, the psychoactive ingredient in marijuana is almost a perfect double of anandamide, produced naturally in your body. When you ingest THC, it binds to CB1 receptors in the brain and body, altering emotion, memory, and cognition, often amplifying pleasurable sensations. Considering that THC is an anandamide look-alike that binds with CB1 receptors in the brain, those psychoactive properties make a lot of sense. 

However, there are plenty of other phytocannabinoids that do not interact with receptors in the brain to cause psychoactive effects. It’s true that the cannabis plant (marijuana) is particularly high in phytocannabinoids, but other plants like hemp and even vegetables like broccoli can also contain non-psychoactive, ECS stimulating cannabinoids.

The Non-Binding Cannabinoid: CBD

CBD is perhaps the most exciting phytocannabinoid supplement because it has an unusual set of effects. CBD does not bind directly to either the CB1 or CB2 receptor. Instead, CBD modifies receptors’ ability to bind to other cannabinoids. For example, CBD can reduce a CB1 receptor’s ability to bind with THC.

As a supplement, CBD does much more than your average cannabinoid by acting on the entire ECS. In addition to interacting with cannabinoid receptors, CBD can also regulate the enzymes that help build or destroy naturally occurring endocannabinoids; CBD inhibits FAAH, the enzyme that destroys anandamide. So instead of just being a substitute for anandamide, CBD can function as something closer to a bodyguard, keeping the mood-enhancing substance in bodily circulation. 

Studies have shown that CBD may lessen chronic pain by impacting endocannabinoid receptor activity, and may interact with neurotransmitters to reduce inflammation. In this research, CBD has also produced antidepressant like effects in animal studies, and has been safely used as an insomnia, depression, PTSD, and anxiety. Finally, in this research, CBD has also shown promise as a sort of anti-addictive substance by reducing behavior observed in animals exposed to addictive substances. 

Beyond CBD, there are many other non-psychoactive phytocannabinoids that we are just beginning to understand. For example, CBN may bind to CB1 receptors to decrease eye-pressure without causing any sort of psychoactive high. Meanwhile, CBG may decrease inflammation by binding with CB2 receptors. However, with more than a hundred phytocannabinoids, each of which may have dozens of potential downstream effects, it will take many years and studies to truly understand how each phytocannabinoid works independently. 

To Summarize:

The ECS is an important bodily system that plays a role in everything from sleep to sensibility. It is composed of countless cellular receptors throughout your brain, spine, and organs. When the body is moved out of homeostasis, the ECS uses enzymes to manufacture endocannabinoids like anandamide and 2-AG. In turn, those endocannabinoids bind to and activate CB1 and CB2 receptors, which help trigger cellular responses that bring you back to balance. 

A healthy diet and lifestyle can keep the ECS running smoothly, but strategic phytocannabinoid supplementation can also be used to activate cannabinoid receptors or regulate ECS function. It will take a long time to fully understand how all the different phytocannabinoids stimulate the ECS, but the early research is exciting.

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