What Are Endocannabinoids?

Cannabis has had its share of bad raps. From early propaganda like Reefer Madness to today and the current backlash to the legalization movement.   Regardless of all that, the current therapeutic benefits are in danger of being forgotten. But our bodies won’t let that happen. At this moment, CBD is having a moment. To boot, if our bodies didn’t already contain a biological system capable of interacting with its active chemical compounds, like THC, then we may have long forgotten about the endocannabinoid system.

Tongue tied? Well, that’s just because you may have forgotten to stay up on your own self-care.  

The endocannabinoid system does just that. It serves a vital purpose for our health and well-being because it regulates key aspects of our biology. So, what’s it doing, and how does it work?  

Homeostasis and CBD
 
To understand the human endocannabinoid system, it’s helpful to know a little about one of the most fundamental concepts in biology: homeostasis. And the best way to understand homeostasis is to think of Goldilocks and the three bears, or planets in our solar system.   It’s a matter of too hot too cold, just as it applies to regulation of cell death.  
So maybe it’s time to ask...  

Is Your Endocannabinoid System in Balance?  

Homeostasis is the concept that most biological systems are actively regulated to maintain conditions within a certain range.  

Our body doesn’t want its temperature to be too hot or too cold, blood sugar levels too high or too low, and so on. Conditions need to be just right for our cells to maintain optimum performance, and exquisite mechanisms have evolved to draw them back to balance zone if they move out.  

The body’s endocannabinoid system is a vital molecular system for helping maintain homeostasis—it helps cells stay in their Goldilocks zone.  

Because of its crucial role in homeostasis, the Endocannabinoid system is widespread throughout mammals. It can be found in many vertebrate species.   The three key components of the ECS are:  
Cannabinoid receptors found on the surface of cells.   Endocannabinoids, small molecules that activate cannabinoid receptors.   Metabolic enzymes that break down endocannabinoids after they are used.  

Cannabinoid Receptors  

Cannabinoid receptors sit on the surface of cells and “listen” to conditions outside the cell.  

They transmit information about changing conditions to the inside of the cell, kick-starting the appropriate cellular response. We are indebted to these kinds of cells.  

The two major cannabinoid receptors are referred to as CB1 and CB2.  

These aren’t the only cannabinoid receptors, but they were the first ones discovered and remain the best-studied. As always, unless regulations open, the research won’t follow.  

Still, CB1 receptors are one of the most abundant receptor types in the brain.  

CB2 receptors are more abundant outside of the nervous system, in places like the immune system. However, both receptors can be found throughout the human body.  

The CB1 and CB2 receptors are key players in the endocannabinoid system (ECS). They are located on the surface of many different types of cells in the body.  

Both receptors are found throughout the body, but CB1 receptors are more abundant in the central nervous system, including on neurons in the brain.

​In contrast, CB2 receptors are more abundant outside of the nervous system, including cells of the immune system.
 
Endocannabinoids and Their Role  

There are two major endocannabinoids in cbd oil: Anandamide 2-AG   These endocannabinoids are made from fat-like molecules which are packaged and stored for later use like many other biological molecules (such as fat). Handy!  

Cannabinoids are a class of molecules characterized by their ability to activate cannabinoid receptors like CB1 and CB2. Anandamide and 2-AG are the two major endocannabinoids produced naturally in the body.  

All of these cannabinoids can activate the CB1 and CB2 receptors, although each one has a different potency at each receptor. That’s why they are all important and should be looked at when selecting CBD products.

Does Metabolism Affect CBD?  

The third piece of the puzzle when it comes to cannabis derivatives includes the metabolic enzymes that quickly destroy endocannabinoids once they are used. The two big enzymes are FAAH, which breaks down anandamide, and MAGL, which breaks down 2-AG.  

These enzymes ensure that endocannabinoids that are CBD dominant get used when they’re needed, but not for longer than necessary. Hormones or classical neurotransmitters, which can persist for many seconds or minutes,  get packaged and stored for later use. It’s like having a backpack of the best known effects of CBD.  

The three key components of the ECS can be found within almost every major system of the body. When something brings a cell out of its zone, these three pillars of the ECS are often called upon to bring things back, thus maintaining homeostasis.

The one thing we need when trying to help with neurological disorders. In other words, the ECS helps bring things back to the biological Goldilocks zone.  

Below we will consider examples of how the ECS helps maintain homeostasis in two areas:   The firing of brain cells in the nervous system The inflammatory response of the immune system.  

Endocannabinoid Regulation of Brain Cell Firing  

Brain cells (neurons) communicate by sending electrochemical signals to each another. Each neuron must listen to its partners to decide whether it will fire off its own signal at any given moment. However, neurons don’t like to get too much input—there’s a Goldilocks zone. If they get overloaded by signals, it can be toxic. That’s where endocannabinoids come in.  

How Does Cannabis Consumption Affect the Brain?  

Under normal circumstances, a given brain cell will get just the right amount of input from its partners—not too much, not too little. However, some of its partners can become overactive, and send an excessive number of signals.  

The neuron that’s listening will detect this, and release endocannabinoids that tell the other neuron to quiet down.  
This kind of mechanism helps maintain homeostasis because it helps prevent neurons from sending out too many signals.  

Endocannabinoids travel backwards, like the energy within fat cells, which is why they’re known as retrograde signals.   Most of the time, information flow between neurons is strictly in one direction, from “sender” neurons that release neurotransmitter signals to “receiver” neurons that listen to those signals.

Endocannabinoids allow receiver neurons to regulate how much input they’re getting, and they do this by sending retrograde signals (endocannabinoids) back to overactive sender neurons.  

But the brain isn’t the only organ that needs to maintain homeostasis. Every other system of the body, from the digestive to the immune system, has to carefully regulate how its cells are functioning. Proper regulation is crucial for ensuring survival.

Endocannabinoid Regulation of Inflammation

Inflammation is a natural protective reaction the immune system has in response to infection or physical damage.   The purpose of inflammation is to remove pathogens (germs) or damaged tissue. The inflamed area is produced by fluid and immune cells moving into the area to do the dirty work and return things to their Goldilocks zone.  

It’s important that inflammation be limited to the location of damage and doesn’t persist longer than needed, which can cause harm.

Chronic inflammation and autoimmune diseases are examples of the immune system getting activated inappropriately. When that happens, the inflammatory response lasts for a less than ideal time, which cause chronic issues, and even directs blame at healthy cells, impeding their ability to work properly.  

This is where autoimmune disorders start to rear their ugly heads. Enter Arthritis.  

Cannabis and Arthritis  

In general, endocannabinoids seem to suppress or limit the immune system’s inflammatory signals.   CBD and THC 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 disease.   Consider a normal immune response triggered by a bacterial infection.  

First, immune cells detect the presence of bacteria and release proinflammatory molecules that tell other immune cells to come and join the fight. Endocannabinoids get released as well, which also signal to other immune cells for assistance and likely help limit the inflammatory response so it isn’t excessive.  

By tightly regulating inflammation, the immune system can destroy germs or remove damaged tissue, and then stop. This prevents excessive inflammation, allowing cells, and thus the body, to return to the Goldilocks zone.  

The Endocannabinoid System and Inflammation  

Regular wear and tear of cells of the immune system are possible when a defensive attack against bacteria is underway.

These campaigns include pro-inflammatory molecules and they also stand against the impending brigade.  

Endocannabinoids also get released, and likely help regulate the magnitude and extent of this inflammatory response.   The reason that plant cannabinoids have psychoactive and medicinal effects within the body is, in large part, because we have an endocannabinoid system (ECS) that they can interact with.  

For example, THC gets you high because it activates the CB1 receptor within the brain. Endocannabinoids like anandamide also activate CB1.  

So why aren’t we constantly high? And Why Is CBD Legal?  

This is the golden question right? Although CBD isn’t legal across the board, there are a couple big reasons we aren't’ always high. First, is that it’s not a proper defense mechanism.

Second, THC doesn’t interact with CB1 receptors in exactly the same fashion as the body’s natural endocannabinoids. This means you’re safe from drug tests, depending on the CBD source, and safe from lions and tigers, within reason.  

The metabolic enzymes that quickly break down endocannabinoids like anandamide don’t work on THC, so THC lingers around for much longer.   It’s important to remember that molecules like cannabinoids and other neurotransmitters rarely interact with only one receptor type; they often interact with many.

The plant-based cannabinoid CBD illustrates this nicely, as it interacts with numerous receptor types in the brain. So, while plant cannabinoids may activate the same cannabinoid receptors as endocannabinoids, they will likely interact with several other receptors and therefore have distinct effects. 

CBD is also interesting because it can affect overall levels of endocannabinoids in the brain, referred to as “endocannabinoid tone.” CBD inhibits the FAAH enzyme, which breaks down anandamide.

Thus, CBD can increase anandamide levels by preventing FAAH from breaking it down. Inhibiting the FAAH enzyme has been shown to be a useful strategy for treating anxiety disorders, and some of CBD’s anti-anxiety properties may come from its ability to inhibit this enzyme and thereby increase endocannabinoid tone. 

Because of its vital role in making sure that cells and systems remain in their physiological Goldilocks zone, the ECS is tightly regulated; it gets deployed exactly when and where it’s needed. However, this doesn’t mean that activating the ECS, through consumption of cannabis or by any other means, will always make things just right.  

Like any other complex biological system, the ECS can go awry. “If deviation from physiological homeostasis is prolonged, due to either external factors or chronic pathological conditions, the eCS can lose its time- and space-selective mode of action and start affecting inappropriate cells,” Dr. Di Marzo explained. “In these cases, the ECS, instead of being beneficial, may actually contribute to disease progression.” It’s important to remember that activating the ECS, through cannabis consumption or by any other means, isn’t a cure-all. Like most of biology, it’s complicated.

By understanding the biological Goldilocks principle (homeostasis), and how the ECS illustrates this at the cellular level, we can more deeply appreciate why we have an ECS to begin with, and how a variety of cannabis-based therapies might actually work. The presence and critical function of the ECS across many systems of the body, including the nervous and immune systems, explains why such a wide variety of ailments and disease states are responsive to cannabis-based interventions.  

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