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How Does CBD Work in the Body?

If you are familiar with the acronym CBD, you may have heard that it works with our body in a very natural way. The reason for this is because every invertebrate, including humans, has a system within their body that is capable of utilizing CBD, or cannabidiol, a naturally occurring plant compound. Each one of us has a body system called the endocannabinoid system (ECS). This system is what allows CBD and other cannabinoids (there are currently over 113 known) to bind to receptors that when activated or inhibited, can have a myriad of positive effects.

What is CBD?

What is the Endocannabinoid System (ECS)?

The Endocannabinoid System is a series of receptors that run throughout the body, overlaying the nervous system. This system is specifically responsible for and manages the use of endocannabinoids, created by the body itself. The ECS is believed to help keep the body in balance, just like many other vitamins and minerals, and is an essential part of the whole body system. Just as with vitamins and minerals, we can be deficient at times, and this is where CBD and other cannabinoids come into play, as they mimic the body's own endocannabinoids.

Who discovered the Endocannabinoid System?

The process to the final name of the system took about 30 years. Starting in 1964, THC was first discovered and isolated from the cannabis plant by Professors Yechiel Gaoni and Raphael Mechoulam. They termed the isolated tetrahydrocannabinol as a “cannabinoid.” Many years later, in 1988, Professor Allyn Howlett and Researcher William Devane discovered receptor sites on the brain that responded to cannabis. The receptors had a high affinity for and were directly responsive to the cannabinoids found in the Cannabis Sativa plant. The team termed the receptors as “cannabinoid receptors.” In 1992, Analytical chemist, Lumir Hanus with the support of William Devane, isolated the first known endocannabinoid from the human brain. This endocannabinoid meant that the body was naturally producing the chemical. This is where the prefix “endo” arises, meaning within the body. This endocannabinoid would need to be regulated by the body. This regulation would occur by a system they termed the “endogenous cannabinoid system.” This term was later combined into the familiar endocannabinoid system “ECS.”

What are Endocannabinoids?

Endocannabinoids are neurotransmitters that bind to receptors found throughout the body. These specialized receptors can be found in the brain, organs, connectives tissues, skin, glands and immune system cells. Endocannabinoids are believed to be an important part of maintaining homeostasis within the body by allowing internal functions to operate at their peak performance. The two endocannabinoids that have been identified to date are anandamide (AEA) and 2-arachidonoylglyerol (2-AG).

Do We Have CBD in Our Body?

We have many endocannabinoids in our body that are created by our own body. CBD is considered a phytocannabinoid as it is from a plant source rather than made within the body. This means that we do have endocannabinoids because our own body makes them, but we do not have phytocannabinoids naturally, unless we ingest them. When we ingest the phytocannabinoid CBD, it mimics our body's own natural endocannabinoids and thus is able to signal our endocannabinoid system into action.

How Does CBD Bind to Receptors?

Receptors are like a baseball glove that can only catch one type of ball. Different types of receptors are made to catch different types of balls. Cannabinoids are different types of balls. When cannabinoids are “caught,” they will cause the catcher to behave in a particular way. They can only be caught by the right kind of receptor. When CBD enters the bloodstream, it is able to bind to certain types of receptors.

Which Receptors Does CBD Bind To?

Cannabidiol (CBD) is a pleiotropic compound in that it has multiple effects that are found through multiple molecular pathways. To date, there have been more than 65 molecular targets for CBD identified. You may have heard of the CB1 and CB2 receptors that have been identified to exist throughout the body. These receptors have the most affinity for (or are designed to catch) specific endocannabinoids, as well as the phytocannabinoid THC. CBD, however, does not bind to these receptors like THC to activate them, but rather influences it in some way as to decrease their affinity for THC. This is beneficial for many looking to control the psychoactive nature of THC in the body. Serotonin receptors 5-HT1A have been shown to have direct activation when high concentrations of CBD are ingested, as discovered by Jose Alexandre Crippa of the University of San Paulo, Brazil. 5-HT1 receptors are naturally activated by the neurotransmitter serotonin. These receptors are found throughout the body and are believed to control the neurological processes of anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting. The 5-HT receptors trigger a cascade of molecular responses that when activated, will produce an excitatory or an inhibitory response, depending on the location and context of the chemical message. Vanilloid receptors TRPV1 have also been shown to bind to CBD with a high affinity. The receptor is responsible for pain perception. TRPV stands for “transient receptor potential cation channel subfamily V.” TRP receptor variants are known to mediate the effects of a wide range of medicinal herbs. Capsaicin, the compound found in chili peppers also activates this receptor, and is a familiar compound found in many pain-relief creams. Anandamide, an endocannabinoid has been identified as one of the body's natural neurotransmitters for this receptor. There are instances where CBD will bind to a receptor that will cause an antagonistic effect. This means that it will prevent the cascade of responses that would normally be activated by a particular molecular pathway. The receptors GPR55 (G-protein receptor) and PPARS (nuclear receptor) have a high affinity for CBD that when bound, will have an antagonistic on cell proliferation.

How Does CBD Act as a Re-uptake Inhibitor?

When CBD is in high concentrations in the body, it can behave in the same way as other endocannabinoids, making more of that endocannabinoid available for use within the body while the body is using the CBD at the same time. For instance, in the nuclear cell receptor PPARS, the CBD must first enter the cell. To do this, it must use a protein to pass the cell wall. This protein, while being used by the CBD, cannot be used by the endocannabinoid anandamide, but the CBD will complete the job of the anandamide once in the cell. This means that there is more of the naturally occurring substance that can be utilized by the rest of the body, allowing for homeostasis.

How Does CBD Act as a Positive Allosteric Modulator?

When the compounds and cannabinoids are consumed, they can have limited benefit in the body and mind. This is because the other compounds and cannabinoids help the others work more effectively. You will feel some benefits if the compounds are taken in isolated form, however, the Entourage Effect that is created when compounds and cannabinoids are able to work synergistically with each other. Here is a simple analogy. When you eat a burger with no toppings, you are getting the benefit of the burger, and it will be find just on its own, but not particularly satisfying. If you add all the fixings to that burger, such as cheese, lettuce, tomato, not only does the burger taste better, but it also works better in your body because of the added nutrients. When looking to try a new wellness product, full-spectrum may not be the way to go. It has the potential to create unpredictable effects within the mind and body, depending on your body type. Look for products that contain broad-spectrum extracts or isolate forms of cannabinoids that have been combined back together.

Taking CBD and THC Together – Negative Allosteric Modulation

When taken concurrently with THC, CBD can help ease the feelings of being “high” with an antagonistic effect. In other words, CBD can put a cap on how much psychoactive effect is tolerated by a given dose in the body. Canadian scientists have identified CBD to be a negative allosteric modulator of the CB1 receptor in this regard. The negative modulation means that the CBD is making it harder for THC to bind to the receptor. This can be beneficial for those seeking the effects of THC, which are numerous when involving the CB1 and CB2 receptors, but do not desire the psychoactive effects.

Check out more information about CBD and the full article on How CBD Works in the Body.

Author: A.J. Varela, Biologist

Date: 02/15/21

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