What is the Endocannabinoid System and how does CBD work?

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Vincenzo DiMarzo, an Italian scientist, proclaimed in a 1999 Trends in Nueroscience paper, that the endocannabinoid system (ECS) is responsible for enabling us to "eat, sleep, relax, protect, and forget" (1) and that it plays an essential role in order for our bodies to remain healthy.

We analyze these five primary roles in more detail:

  • Eating: The Endocannabinoid System (ECS) is highly influential in regulating hunger and satisfaction levels.
  • Sleeping: It helps you relax, fall to sleep and enable a good night's rest.
  • Relaxing: This ECS promotes mental wellbeing (and therefore physical wellbeing) by reducing stress.
  • Protecting: It helps in  stimulating production of new brain cells to safeguard brain health, the ECS when performing correctly encourages healthy metabolism, and adjusts your immune system so you can fight off infections.
  • Forgetting: This may seem odd, but forgetting is an intergral part of healthy living. If someone remembered every detail of everything that happened every second of the day, the person would not be able to act in a national manner! The ECS manages both essential short term and long term memory and has a vital role in "memory extinction," or letting go of things that are not worth remembering.


The ECS is the master regulator of the body, controlling all these processes.

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The Controller of All Events 

The individual who plays the role of the chief leader, the one who can alter the course of events, is known as the master regulator. This same person can be referred to as the controller of all events.

Envision yourself in a setting with four walls encompassed by 100 thermostats. Every one of these thermostats controls a significant physiological capacity that keeps us solid. Consider the Endocannabinoid System as the entirety of those thermostats joined into a solitary, powerful system that is engaged with controlling practically all human organic functions.

It is possible that changing the activity of the endocannabinoid system could be beneficial in treating a wide range of human diseases?

The ECS functions as a regulator of a multitude of physiological processes, including inflammation control, glucose metabolism, brain cell production, wound healing, pain perception, and blood pressure.

In the face of an emergency, your body produces stress hormones such as cortisol and adrenaline to help you react in an appropriate manner - the classic "fight or flight" response. When the situation stabilizes, the endocannabinoid system (ECS) reduces the production of these hormones and returns them to normal levels.


When you are ill, the Endocannabinoid System (ECS) raises your body temperature to combat the infection.

Once the invader has been defeated and the fever is no longer needed, the endocannabinoid system (ECS) reduces the strength of the immune system to return body temperature to its usual state. But when the dimmer switch is not functioning correctly, the body can't control the inflammatory response and healthy cells can be damaged. Autoimmune illnesses are a sign of ECS malfunction.

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Researchers in the medical field have found that the Endocannabinoid System (ECS) has been disrupted in many illnesses, such as cancer, diabetes, Alzheimer's, pain, sleep disorders and addiction. This led to the 2013 NIH study, conducted by Pal Pacher and George Kunos, which showed that "modifying the Endocannabinoid System could be a helpful approach to treating a wide variety of diseases that affect humans".


It is understandable why medical cannabis could be of use for several ailments given that both THC and CBD act on the endocannabinoid system.


In the late 1990s, researchers had acquired knowledge of the main aspects of the endocannabinoid system, as it is known at present. This system comprises of three primary components:


Cannabinoid receptors : These are like small openings that sit on the outer layer of cells in the brain, central nervous system, and other organs. They detect essential signals about what's happening in the body, allowing the cells to act appropriately. There are two primary types of cannabinoid receptors: CB1 and CB2. Both are distributed throughout the body, but CB1 receptors are mainly concentrated in the brain and central nervous system and CB2 receptors are mainly located in the immune system. Additionally, both varieties of cannabinoid receptors can be found in the skin, liver, kidneys, heart, and other internal organs.


Our bodies contain Endocannabinoids, which act just like the cannabinoids found in cannabis. The two most common of these are 2-Arachidonoylglycerol (2AG) and anandamide, a molecule that takes its name from the Sanskrit word ananda, meaning bliss due to its mood-elevating effects. Both of these molecules interact with the same receptors as those present in the cannabis plant and act as a key to unlock them.


Metabolic Enzymes : These proteins systematically speed up chemical reactions and oversee the amount of endocannabinoids present. They are responsible for synthesizing endocannabinoids when necessary and degrading or eliminating them once they have done their job.




A Quite Incredible Molecule - CBD

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CBD has gained a considerable amount of recognition in recent years due to its many potential health benefits. The compound, which is derived from the cannabis plant, has been found to have properties that may help with issues such as anxiety and pain management. Additionally, CBD is believed to have anti-inflammatory effects and could prove to be beneficial in treating certain forms of epilepsy. As research continues, more and more people are discovering the potential of this molecule as a viable alternative to traditional medications.


In recent years, the Endocannabinoid System (ECS) has seen the addition of a fourth element; transport molecules. These act like shuttles, carrying endocannabinoids to their desired locations. These molecules, known as fatty acid binding proteins, are essential to the functioning of CBD.


The discovery of the endogenous cannabinoids (2AG and anandamide, produced by our body) by researchers was the first of its kind.


They questioned how they could traverse the liquid inside the body. After all, blood is mainly composed of water, and cannabinoids are fat-based lipids - both of which are famously insoluble. The answer was discovered in 2009 when particular molecules to transport endogenous cannabinoids were identified.


The fatty acid binding proteins, as their name suggests, bind to certain fatty lipids such as cannabinoids. In the bloodstream, these proteins work like a canoe, transporting cannabinoids to their destination. This includes taking them across the cell membrane, and into the cell itself, where they can interact with receptors near the nucleus.


PPARs, otherwise known as nuclear receptors that control gene expression and energy metabolism, have the capacity to transport CBD to different places in the body. This might explain why CBD has the capacity to provide such remarkable therapeutic effects.


Once you take CBD, it is like it moves to the top of the cannabinoid queue, displacing 2AG and anandamide, and secures a prominent seat on the canoe. This leads to your endogenous cannabinoids staying on the exterior of your cells for a longer duration, providing them with more time to interact with your CB1 and CB2 receptors until the next ride arrives to transport them to the interior of the cell, where they are eventually deactivated by metabolic enzymes.


Essentially, CBD works to extend the lifespan of our endocannabinoids in order to provide more helpful effects. It is similar to when you increase the strength of weak biceps by working out and exposing them to extra stimulus. In a similar way, CBD increases the "tone" of the endocannabinoid system by exposing it to an increased amount of cannabinoid activity. This might be an essential process that CBD utilizes to secure the brain, buffer stress, and help to fight illnesses.


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CBD is frequently discussed as being non-psychoactive, but is this really true? To answer this question, one must understand what being psychoactive means. Psychoactive substances are those that act on the brain and produce alterations in mood, thinking, and behavior. THC is the most famous psychoactive cannabinoid, but as CBD has the ability to act on the barin and produce changes in mood thinking and behavior - many CBD companies incorrectly state that CBD is non-psychoactive.


Controlling Cell Size


The act of regulating the volume of cells can be referred to as cellular volume control.


One method of how CBD helps to improve the endocannabinoid tone is by taking up room on the canoes and thus lengthening the lives of 2AG and anandamide. However, that is not the only way CBD interacts with the endocannabinoid system. Aside from increasing the levels of endocannabinoids through delaying their re-uptake and breakdown, CBD can also change and modify the performance of cannabinoid receptors.


By taking CBD, it can raise the levels of the natural cannabinoids present in your body and also modify the way your cannabinoid receptors work.


THC engages itself to both CB1 and CB2 cannabinoid receptors in a way that is similar to a key being inserted into a lock and activates these receptors, consequently leading to a physiological response (diminished pain, less inflammation, decreased blood pressure, a state of mild euphoria, relaxation, etc.). On the other hand, CBD does not work in the same way. Instead of directly connecting with cannabinoid receptors to launch a signal itself, CBD adjusts the signaling that has already been set off by THC or an endogenous cannabinoid.


Scientists are in the process of attempting to understand precisely how CBD works, and the science is still being developed, but here's what we understand so far. Preliminary (in vitro) studies suggest that CBD serves as an allosteric modulator at the CB1 receptor, implying that it affects how the receptor signals without prompting it to signal. Think of the CB1 receptor like a dimmer switch or volume control knob -- CBD adjusts it a bit but not completely. This appears to be one of the ways CBD decreases the limit on THC's tricky psychoactivity and reduces the high, which is caused by direct CB1 receptor activation.


At the same time, CBD boosts CB2 receptor activity, which is responsible for inflammation and immune system responses. Despite the fact that CBD does not directly bind to the CB2 receptor, it still manages to create an anti-inflammatory reaction and other CB2-mediated effects. This is done by adjusting the ECS through adjusting CB1 and CB2 receptor function in opposite directions, lessening the former and strengthening the latter. This combination has been shown to have extremely beneficial effects, especially when it comes to metabolic disorders, obesity, liver disease, and other conditions associated with the Western diet.


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In summary, CBD can elevate your endogenous cannabinoid compounds, like anandamide and 2AG, which interact with your cannabinoid receptors and set off a signal. Additionally, CBD can adjust the manner in which your cannabinoid receptors work, lessening the activity of CB1 while increasing CB2, thus creating a balanced state in your body and promoting wellness. 




References and Further Reading:

  1.  "Endocannabinoids: Endogenous Cannabinoid Receptor Ligands with Neuromodulatory Action," V. DiMarzo, D. Melck, T. Bisogno, and L. DePetrocellis Trends in Neuroscience article from February 1999.
  2. A 2009 British Journal of Pharmacology report from D. Fraga, C.I.S. Zinoni, G.A. Rae, C.A. Parada, and G.E.P. Souza .
  3.  al Pacher and George Kunos  2013 FEBS Journal article, "Modulating the Endocannabinoid System in Human Health and Disease: Successes and Failures."
  4.  Hui-Chen Lu and Ken Mackie 2016 Biological Psychiatry review, "An Introduction to the Endogenous Cannabinoid System."
  5.  2019 Molecules piece from Fan Hong, Shijia Pan, Yuan Guo, Pengfei Xu, and Yonggong Zhai examines the role of PPARs as nuclear receptors involved in nutrient and energy metabolism.