The Endocannabinoid System, how does it work?

Endocannabinoid Glossary:

• Endocannabinoid system (ECS): Intercellular communication system in charge of balancing metabolic processes and optimizing the function of our body.
• Phytocannabinoid: A cannabinoid naturally produced by a plant.
• Endocannabinoid: Cannabinoid naturally produced by the human or animal body.
• Synthetic cannabinoids: Cannabinoids created in laboratories.
• Cannabinoid receptor: Receptors that make up part of the ECS and are located throughout our body, endocannabinoids/phytocannabinoids bind to these receptors and activate them.
• Cannabinoid enzymes: These are enzymes that synthesize and break down cannabinoids.
• Homeostasis: The ability to maintain relative constancy of the composition and properties of an organism. The stability and balance of our mind and body.

What is the endocannabinoid system? Why is it important?

The endocannabinoid system, hereinafter ECS (Endocannabinoid System), is another system in the body, like the circulatory or immune system. It is one of the most fundamental systems of our body. However, it is quite common to be unaware of its existence and even more so know how it works. Today we will explain what the ECS does, how it works, and why cannabinoids can be beneficial for our body.

Discovering the ECS

Why have you never heard of ECS? Probably because it was discovered very recently, specifically during the 90s, through the study of phytocannabinoids such as THC and CBD. While investigating phytocannabinoids (Fun fact: It was sponsored by the United States with the mission of demonizing cannabis), researchers discovered that humans, and most other mammals, have cannabinoid receptors in our bodies. This was due to the discovery of one of the fundamental receptors of the ECS, the CB1 receptor. These findings led to the discovery of the first naturally produced endocannabinoid in 1992. This was anandamide, it is also known as the bliss molecule. These two events led to the discovery of the endocannabinoid system, which owes its name to the plant that made its discovery possible, cannabis.

Definition: Endocannabinoid System (ECS)

The endocannabinoid system is a complex intercellular communication system, similar to a neurotransmission system, but it spreads to other organs and tissues in the body, not just the brain. It’s like a thermostat by regulating various physiological functions of our body, balancing and stabilizing the activity and production of different organs and systems of our body. The responsibility of the ECS is to balance metabolic processes and optimize the function of our bodies. It plays a crucial role in regulating our physiology, mood, and day-to-day experience. The ECS is a difficult system to understand due to the short amount of time that it has been recognized and investigated, in addition to the complexity found in each human being.

Functions related to the Endocannabinoid System

What are the different parts of the ECS and how does it work?

To recapitulate, the ECS is a system of communication between cells that is found throughout our body. The ECS consists of three important components:

• Endocannabinoids: Cannabinoids that our body produces naturally which then bind and activate our cannabinoid receptors.
• Cannabinoid receptors: Proteins activated by endocannabinoids/phytocannabinoids, which receive and transmit information.
• Enzymes: Specific enzymes that synthesize and break down cannabinoids (endo + phyto).

 Organs and systems where we can find the Endocannabinoid System The receptors are:

• CB1 receptors: Mostly found in the central nervous system and especially abundant in the brain. They hang around areas related to cognitive functions, memory, anxiety, pain, sensory perception, visceral perception and motor coordination. They can also be found around some areas of the peripheral nervous system.
• CB2 receptors: Mainly found in the peripheral nervous system and especially abundant in cells with immune function.
• GPR55 Receptors: Can be found in the adrenal glands, digestive system, central nervous system, and spleen.
• TRPV1, GPR18, 5-HT3, PPARs: Receptors and receptor channels which are still in the process of being studied further.

How CB1 receptors activate brain function The distribution of cannabinoid receptors is totally different from any other receptor we have. What we see here is that they’re everywhere. It’s what defines the ECS, its presence is totally global in our body, it’s omnipresent! CB1, the first receptor to be discovered, has been under the microscope for much longer so we have a lot more information. Its abundance in our brain can be seen in the graph below.

The endocannabinoids, that we know of so far:

• Anandamide:Is the first endocannabinoid discovered therefore we know much more about it compared to other endocannabinoids. Its name comes from the word "ananda" which in Sanskrit means bliss, a state of serenity, spiritual peace and happiness.It is synthesized in the brain where memory, motivation, and other higher cognitive processes and movement control are managed. In this way it has the ability to influence physiological systems such as pain, appetite, pleasure and reward. Anandamide binds to our cannabinoid receptors, but the same enzymes that synthesize Anandamide will also quickly break it down.

 Molecular structure of Anandamide

• 2-arachidonoylglycerol (2-AG): Known as 2-AG, because it’s real name is impossible to say, is found mostly in the brain. 2-AG is an emetogenic cannabinoid, that means it’s responsible for an important physiological response, which is vomiting. The antiemetic effects of other cannabinoids, mediated by CB1 and CB3 (GPR55) receptors inhibit their activity and suppress the reflex or impulse of vomiting and nausea.
• Other recognized endocannabinoids: 2-arachidonyl glyceryl ether, virodamine, N-arachidonoyldopamine.

So how does all this magic work?

The ECS and its respective parts, endocannabinoids and receptors, interact with each other as if they were a lock and a key. The receptors would be the lock and the endocannabinoids, or phytocannabinoids, would be its key. Let's get a little more scientific: Cannabinoid receptors are proteins present in the cell membrane that act as a lock for endocannabinoids (cannabinoids derived from fatty acids produced by our bodies). Endocannabinoids, endogenous lipids, act as a perfect key for this lock, they bind to the receptors and when this occurs the receptor is activated. This activation produces changes within cells that lead to the ECS’s final actions on the body's physiological processes. Phytocannabinoids (cannabinoids from the cannabis plant) and many synthetic cannabinoids bind to this lock in the same way and offer effects that are analogous to endocannabinoids, or even enhance their effects.  How the ECS works

What factors does the ECS affect (That we know of now)

• Energy balance and metabolism
• The response to stress
• The female reproductive system
• The autonomous nervous system
• Pain response
• Temperature regulation
• The immune system
• Sleep
• Physical exercise
• Memory
• Mood
• Appetite

So let’s remind ourselves that the main function of the ECS is regulating and achieving homeostasis in our body. It is essential for our body to achieve that balance and everyday our systems go to work to make that happen, and the ECS is their boss.

How does Cannabidiol (CBD) interact with the ECS?

Cannabinoids, like CBD, interact with cannabinoid receptors. CBD helps improve ECS function in turn helping the ECS regulate and balance the rest of our organs and systems. Something very promising that is being studied at the moment is the possibility of CBD enhancing the effects of endocannabinoids in our body. Studies suggest that CBD can inhibit cannabinoid enzymes, responsible for breaking endocannabinoids down. Currently, studies indicate there are different types of interactions between the ECS and different phytocannabinoids. An easy example is CBD, whose use does not activate receptors in the same way as, for example, THC.

Every human has an endocannabinoid system and we can all enhance it, with or without cannabis.

The endocannabinoid system exists in every human and is active even if you have never used cannabis. It is very important to enhance our ECS for our health. CBD can be a way to improve and enhance our ECS and feel more effective and balanced in the activity of our body. Learn about our products. However if you aren’t interested in trying phytocannabinoids, there are other ways to enhance your endocannabinoid system. Check out our blog on 10 ways to enhance the endocannabinoid system, it’s full of tips!

Where do we go from here?

We still don't know much about the endocannabinoid system, our endocannabinoids, and how powerful phytocannabinoids can be. Every day researchers study more and everyday more is discovered. There are surely more receptors, more endocannabinoids, and more components of ECS that have yet to be discovered. The important thing is that we continue to push our governments and support our institutions to study this fascinating system (and the plant that allowed us to discover it!) so that we can further continue to understand our organism and the connection between mind and body. Written and illustrated by: Christina Schwertschlag Edited and published by: Claudia Nicolás

Bibliography

ECS

• Endocannabinoid System. Project CBD.
• El Sistema Endocannabide. Fundación canna.
• A simple guide to Endocannabinoid System. Healthline.

Cannabinoid receptors and the ECS

• Shenglong Zou and Ujendra Kumar. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. 2018
• Mariano García. Endocannabinoid System (ECS) and phytocannabinoids

Anandamide

• J Neurochem et al. Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. 1993
• D. Matthew Walentiny et al. The endogenous cannabinoid anandamide shares discriminative stimulus effects with ?9-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice. European Journal of Pharmacology Volume 656, Issues 1–3, 10 April 2011, Pages 63–67

2-AG

• J Pharmacol Exp Ther. The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannnabinoids.2002