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The Endocannabinoid System (ECS) & CBD


The endocannabinoid system, or ECS, is a complex system of cellular signaling present in all vertebrate animals and necessary for our very survival. Discovered in the 1990s while researchers were exploring THC, a well-known cannabinoid present in marijuana, the ECS is now known to be involved in several other physiological systems related to mood, stress, appetite, memory, reproduction, inflammation, sleep, pain and anxiety. Endo, meaning “in” is an important deviation from the word cannabinoid because It implies that these cannabinoids are made within the body and not obtained exogenously from a plant.

Essentially, the ECS keeps everything in balance. If you start to sweat on a hot day, it is the ECS that kicks in monitoring your internal environment temperature and stimulates the sweating or cooling down process. It is responsible for homeostasis in the body.



The ECS Tone

The ECS operates in a continuous cascade of enzymatically orchestrated pathways of which the endocannabinoids flow, attach to receptors, are degraded and synthesized as needed.  This may all happen congruently in a multi-system fashion. This is called the ECS tone. ECS tone is an indication of the overall state of your ECS.  Obesity, for example, represents an elevated hypothalamic endocannabinoid tone.  Diabetes is another example of a dysregulated tone.  The tone is the overall action generated by the receptors, endocannabinoids, and enzymes all working in sync throughout the body creating a rhythmic flow that leads to balance in the body. A lack of balance often involves a dysfunctional ECS.


Endocannabinoid system image 1
Simulation of
the Endocannabinoid system

How Does the Endocannabinoid System Work?

The ECS system is a vibrant and alive system whether you are aware of its processes or not. Endocannabinoids are produced within the body which is why we have receptors for them located in all our major organ systems. Cannabinoid receptors sit on the outside of cells monitoring for conditions both inside and outside the cellular wall to observe changes in cellular activity. Enzymes then respond to changes in cellular activity by degrading the endocannabinoids no longer needed.

When signals are received at the receptor that an endocannabinoid is needed, it is made immediately and secreted to attach to the cannabinoid receptor where it is then taken up into the cell and tells the cell how to secrete other substances like hormones or neurotransmitters such as serotonin. They affect how other messages are sent, received and processed by other cells.

There are 3 major components to the ECS system

  •       Endocannabinoid receptors
  •       Endocannabinoids
  •       Enzymes that help break down endocannabinoids and cannabinoids

What are the two main cannabinoid receptors?

The two main cannabinoid receptors most studied are CB1 and CB2. CB1 are the most abundant receptors in the brain while CB2 are found outside of the nervous system such as in immune cells. The receptors act as a doorway for the cannabinoids to enter the cell. Both endocannabinoids and cannabinoids from plants can bind to the CB1 and CB2 receptors.

What are the two major endocannabinoids?

Unlike THC, endocannabinoids are produced within the body and bind to the CB1 and CB2 receptors. These two endocannabinoids are:

  •       Anandamide
  •       2-arachidonoylglycerol (2-AG)

Relationship between THC and endocannabinoids

These endocannabinoids are not mind-altering, addictive chemicals such as THC is. That is where so much of the public confusion comes in. THC may be similar in structure to anandamide; however, it is not the only plant-based cannabinoid being studied as having effects in the ECS system.

Relationship between THC and CBD

Cannabidiol, or CBD, is another cannabinoid under study that does not have the psychoactive effects associated with the plant-based cannabinoid THC. Cannabinoids are compounds found in the cannabis sativa plant of which THC and CBD are the most actively studied cannabinoids to date. CBD is the second most abundant cannabinoid after THC in the cannabis plant.  In addition, a total of 8 other major ones have been identified with a total of over 100 confirmed to date.

How Do Endocannabinoids Work?

Endocannabinoid release occurs immediately after bodily biosynthesis with no intermediate storage for “later use” making them ideal homeostatic modulators in real time. This is seen, for example, in appetite regulation. Endocannabinoids regulate appetite and food intake through stimulation of the CB1 receptors which stimulate the release of hunger/satiety hormones. This all happens relatively rapidly with little thought; it is just an occurrence of “balance” between hunger and satiety. Homeostasis.

The role of enzymes

Metabolic enzymes that break down the endocannabinoids after they are used are important for maintaining the homeostasis. Two primary enzymes have been isolated that are charged with this duty:

  •       Fatty acid amide hydrolase or FAAH
  •       Monoacylglycerol acid lipase (MAGL)                    

FAAH breaks down anandamide and MAGL breaks down 2-AG. These enzymes guarantee that endocannabinoids are used for as long as needed and no longer. This is a distinguishing factor of these enzymes from the actions of hormones or other regulating signals like neurotransmitters which can persist for seconds, minutes or packaged and stored for later use.

These enzymes cannot break down plant-based cannabinoids, a limiting factor in cannabinoid research relative to disease treatment. This means that if an active dose of cannabinoids is found for a particular illness the exact dosage must be determined because the natural homeostatic mechanisms of the ECS will not be able to regulate the exogenous cannabinoids.

Endocannabinoid Deficiency

As we learn more about the ECS we are discovering diseases that may be classified as endocannabinoid deficiency diseases. Medical science has termed these clinical endocannabinoid deficiency dysregulation diseases or CECD for short.

These conditions include:

  •       Fibromyalgia
  •       Migraine
  •       Irritable bowel syndrome
  •       Dysmenorrhea
  •       PTSD
  •       Bipolar disorder

The conditions listed frequently involve more than one physiological system and effective treatment for them has been difficult to unearth. It is only logical that science would look to multisystem treatment modalities such as cannabis to treat multisystem disorders such as the ones just mentioned.


How do Cannabinoids interact with the Endocannabinoid System

How Does THC Interact With the ECS?


THC- (6aR,10aR)-delta-9-tetrahydrocannabinol, (−)-trans-Δ⁹-tetrahydrocannabinol
The structure of Tetrahydrocannabinol, also known as THC


THC interacts with ECS in the same manner as the endocannabinoids do. It can bind to either CB1 or CB2 receptors and is not subject to enzymatic regulation, thus the problem with addiction and mind alteration.  On the other hand, it may help with pain and stimulate the appetite for those who have lost theirs as in cases of anorexia.


How Does CBD Interact With the ECS? 


CBD, cannabidiolum, (−)-cannabidiol[3]
The structure of Cannabidiol, also known as CBD

CBD is a different story. CBD doesn’t make you “high” and doesn’t carry any negative side-effects such as paranoia or delusions. Experts don’t exactly agree on how CBD does work or even exactly what it does, but they hypothesize that it prevents endocannabinoids from being broken down through effects of the enzymes. Scientists do know that CBD doesn’t bind to the CB1 or CB2 receptors in the same manner as THC. Science has proven that CBD prevents the enzyme FAAH from breaking down cannabinoids, unlike THC where enzymes have no effect.

The Endocannabinoid System – Concluding Remarks

The endocannabinoid system is the key to our body maintaining homeostasis. It may one day hold the answers to treatments of diseases that affect multiple organ systems for which we have no treatments. With this in mind, the ECS offers a rich landmine of untapped research and potential therapeutic applications.

We need to further educate others on the important role of the ECS, on cannabinoids and the differences between THC and CBD. Along with more research, we need to keep an open mind as to the application of cannabinoids to therapeutic treatments of multi-system disorders for which we currently have no well-defined treatment protocols.

And, keep in mind that lifestyle activities can alter endocannabinoid tone, and thus, ECS activity. Research has shown that diet, supplements, herbs, weight control, and exercise also modulate the ECS tone. Clinical trials investigating these modalities are sorely lacking and in need of attention.

In conclusion, the ECS may be a newly discovered system, but is old in its presence and seemingly imperative to our existence. Furthermore, the field of pharmacology is now considering all members of the ECS as potential novel therapeutic targets for the modulation of problematic diseases. The discovery of the ECS opened a doorway of the discovery of possible novel therapeutic agents that can be utilized in the form of cannabinoids or related chemical structures to modulate health and disease without the adverse side-effects so often associated with the psychoactive cannabinoid, THC.


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