CBD and the Endocannabinoid System

Mar 3, 2020

Have you ever wondered how CBD affects the body? Below you'll learn all about how CBD interacts with the endocannabinoid system, or ECS, which is present in all mammals and is responsible for establishing and maintaining health.

Homeostasis: Staying in the “Goldilocks Zone”

In order to understand the endocannabinoid system, it is helpful to first have a basic understanding of one key fundamental concept in biology: homeostasis. The best way to understand this is to think about the children’s story “Goldilocks and the Three Bears.”

The key concept illustrated in this classic fairy tale is that the best possible outcome often lies at some point in the middle between two extremes. We don’t want something that is either too hot or too cold, but rather something just right.

Homeostasis is the idea that most of our biological systems are actively regulated in order to maintain a particular set of conditions. Our body doesn’t want its blood sugar to be too high or too low, its temperature too hot or too cold, and so on.

Every condition needs to be just right in order for our cells to maintain an optimal level of performance, and our body has exquisite mechanisms to draw them back to this “Goldilocks Zone” if they become anything less than optimal. The endocannabinoid system (ECS) is a molecular system that is vital for helping the body maintain homeostasis by helping cells stay in their ideal zone.

CBD and Endocannabinoid System

Key Pieces of the Endocannabinoid System (ECS)

The endocannabinoid system (ECS) is widespread throughout the animal kingdom and is present in all mammals due to its crucial role in homeostasis. The key functions of the ECS evolved ages ago and is present in all vertebrate species.

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The three primary components of the endocannabinoid system are:

  • Cannabinoid receptors: located on the surface of a cell

  • Endocannabinoids: small molecules that are responsible for activating cannabinoid receptors

  • Metabolic enzymes: break down endocannabinoids after they have been used

Cannabinoid Receptors

These specialized receptors sit on the cell surface and “listen” to the conditions outside of the cell. They relay information to the inside of the cell about any changing conditions – this then kick-starts a suitable cellular response. There are many different cannabinoid receptors, however, the two major (and most studied) of these specialized receptors are known as CB1 and CB2.

  • CB1 receptors: Located most abundantly in the brain, these receptors interact with THC to produce the euphoric “high” feeling.

  • CB2 receptors: Most abundant outside of the central nervous system and present in specific places like the immune system.

It is important to note, however, that both of these receptors can be found throughout the body.

 

Endocannabinoids

Endocannabinoids are naturally produced molecules that, like plant cannabinoids CBD and THC, are able to bind to and activate cannabinoid receptors (the term “endo” meaning “within”). There are two primary endocannabinoids: 2-AG and anandamide – both consisting of fat-like molecules that sit within the cell’s membrane.

They are synthesized on-demand, meaning that they are produced and consumed exactly when they are need most, as opposed to being packaged and then stored for later use as is the case with many other biological molecules.  

 

Metabolic Enzymes

This is the third piece to the endocannabinoid triad and it consists of metabolic enzymes that are responsible for quickly destroying endocannabinoids after they have been utilized. The two most prominent enzymes are MAGL (responsible for breaking down 2-AG) and FAAH (responsible for breaking down anandamide). The core reason for these enzymes is to ensure that endocannabinoids are used when they are needed, though, not for any longer than necessary.

This is what sets endocannabinoids apart from many of the body’s other molecular signals, such as classic neurotransmitters or hormones – both of which are able to persist for many seconds to minutes or end up being packaged and then stored for later use.

These three primary components of the endocannabinoid system (cannabinoid receptors, endocannabinoids, and metabolic enzymes) are present in almost all of the body’s major systems. If anything brings the cells out of their “Goldilocks Zone” then these three pillars of the endocannabinoid system will often be called upon to set things right, thus maintaining homeostasis.

Below we will discuss different examples of how the ECS is able to help maintain homeostasis in two select areas: the immune system’s inflammatory response, and the regulation of brain cells firing.

 

Endocannabinoid Regulation of Inflammation

Inflammation is the immune system’s natural protective reaction to physical damage or infection. The function of inflammation is to eradicate damaged tissue and/or pathogens (germs). An inflamed bodily area is produced by immune cells and fluid moving into the inflicted area to work to return conditions back to their “Goldilocks Zone.”

It is a necessity that inflammation be limited only to the damaged area and that it doesn’t persist any longer than needed, which would cause additional damage. Auto-immune diseases and chronic inflammation are examples of an inappropriately activated immune system. When this happens, the body’s inflammatory response either targets healthy cells (known as auto-immunity) or persists for too long (resulting in chronic inflammation).

Consider a typical immune system response that would be triggered by bacterial infection. First, the presence of bacteria is detected by immune cells, which then release pro-inflammatory molecules designed to tell other immune cells to assist in the fight. Additionally, endocannabinoids are released to help limit the body’s inflammatory response as to not be so excessive and also signals other immune cells for their assistance.

This tight regulation of inflammation allows the immune system to remove damaged tissue or destroy germs, and then immediately stop – preventing excessive inflammation and allowing cells (and the body by extension) to return to their ideal “Goldilocks Zone.”

 

Endocannabinoid Regulation of Brain Cell Firing

Neurons (brain cells) are able to communicate with each other via the sending of electrochemical signals back and forth. Each neuron is tasked with listening to its partners in order to decide whether or not to send out its own signal at any given moment. It is possible for neurons to get overloaded by signals, which can be toxic. This is where endocannabinoids come into play.

Consider this simplified scenario: one neuron is listening to two others and becomes overactive by sending out too many signals, which are then received by the other neurons that are listening in return. When this happens, the body will produce endocannabinoids and release them specifically in this “loud” region – which then travel and bind to CB1 receptors to transmit a signal that then instructs the neuron to quiet down.

This brings everything back full-circle to the “Goldilocks Zone” and maintaining homeostasis. Endocannabinoids are known as retrograde signals, meaning that they have the ability to travel backwards. Typically, information flows between neurons strictly in one direction – the “sender” neuron releases the initial neurotransmitter signal and the “receiver” neuron listens to the message.

Alternatively, endocannabinoids allow the receiving neuron the ability to send a retrograde signal back to the overactive neuron, allowing it to regulate exactly how much input it is receiving.

The brain is not the only human organ that must maintain homeostasis. Every bodily system, from the immune to the digestive system, is required to carefully regulate exactly how its cells are functioning. Proper regulation is a necessity for ensuring overall health and survival.

 

How Do Plant Cannabinoids (Like CBD and THC) Interact with the Endocannabinoid System?

Plant cannabinoids have a medicinal and psychoactive affect within the body due almost entirely to their interactions with our endocannabinoid system (ECS) – THC, for example, provides an intoxicating effect because of its activation of the CB1 receptor within the brain. Other endocannabinoids, such as anandamide, is also able to activate this particular receptor. If this is the case, then why aren’t we constantly “high?”

This is due to a couple of big reasons.

First off, THC does not interact with CB1 receptors in the same way as the body’s naturally produced endocannabinoids. Secondly, the metabolic enzymes that are responsible for quickly breaking down endocannabinoids (like anandamide), have no effect on THC – meaning that THC is able to linger for much longer in comparison.  

It is paramount to remember that neurotransmitters and other cannabinoids have multiple interactions with a variety of different receptor types. Cannabidiol (CBD), a plant-based cannabinoid, illustrates this nicely due to its interaction with numerous receptor types present in the brain. Plant cannabinoids may activate the same receptors as endocannabinoids, though they likely interact with several additional receptors to have these distinct effects.

Another interesting aspect about CBD is its effect on the overall levels of endocannabinoids in the brain – this is known as “endocannabinoid tone.” It is able to inhibit the FAAH enzyme that is responsible for breaking down anandamide and other endocannabinoids. Therefore, CBD has the potential to increase anandamide levels by stopping FAAH from breaking them down.

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