History of the ECS

In 1988 during a government-funded study at St Louis University School of Medicine Scientists discovered that the mammalian brain has receptor sites that respond to compounds found in cannabis. These receptor sites turned out to be make up the most prominent neurotransmitter network in the human body.

Despite the legal status of cannabis making further research difficult it did not halt it. in 1990 The National Institute of Mental Health identified a second cannabinoid receptor (CB2) throughout the immune system and peripheral nervous system.

After that, in 1992 at Hebrew University in Jerusalem, Scientists discovered the endocannabinoid anandamide and later, other endocannabinoids. These groundbreaking studies helped map the endocannabinoid system.

About the ECS

In order to understand the effects of Cannabidiol (CBD) in the body, we need to understand the Endocannabinoid system (ECS). The ECS is present in all humans, vertebrate animals and even some invertebrate animals. ‘Endo’ or endogenous means inside the body. Cannabinoids are the group of chemicals that affect the system. Therefore endocannabinoids are naturally occurring cannabinoids.

The endocannabinoid system is the largest neurotransmitter network in the human body. It consists of numerous microscopic signalling receptors all across the body. These receptors are already being activated by naturally occurring cannabinoid molecules whether you are using cannabis products or not. The use of CBD and other cannabis derived products stimulate and activate the endocannabinoid system.

The Endocannabinoid System

How the ECS works

The endocannabinoid system is directly responsible for managing critical bodily functions such as appetite, mood, sleep, metabolism, inflammation and the ability to ward off infection or disease.

It is composed of three key components:

  • Cannabinoid receptors which are found on the surface of cells.
  • Endocannabinoids which are small molecules that activate cannabinoid receptors
  • Metabolic enzymes that break down endocannabinoids after they are used.

You will often hear the term homeostasis when discussing the ECS. Homeostasis is the concept that most biological systems are actively regulated to maintain a stable internal environment. ECS components form a crucial molecular system that the body uses to help maintain homeostasis despite fluctuations in the external environment.

Cannabinoid receptors [primarily CB1 & CB2] are located on the surface of cells all around the body. They measure the outside cell conditions then transmit information inside of the cell, implementing the appropriate cellular response.

Endocannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) are synthesised to interact with and stimulate cannabinoids receptors.

Because of its vital role in making sure that cells and systems remain in their physiological equilibrium, the ECS is tightly regulated. It gets deployed exactly when and where it’s needed. After the endocannabinoids perform their necessary function the metabolic enzymes such as fatty acid amide hydrolase (FAAH) immediately break them down.

CBD and the ECS

The most common way of describing how the cannabinoids interacts with the ECS works is the lock and key analogy. This depicts the cannabinoid receptors as a lock and endocannabinoids or phytocannabinoids as keys. Endocannabinoids like anandamide and phytocannabinoids such as THC bind directly to the receptor sites like a key fitting into a lock. A substance which does this is known as an agonist. CBD however, has a low binding affinity to these receptors but it does interact with them in a number of different ways.

CBD’s action within the ECS is mainly indirect. It’s main role is enhancing the effects and levels of anandamide, the bodies’ default endocannabinoid. CBD acts as a FAAH inhibitor which slows the decomposition of anandamide. It also acts as an anandamide re-uptake inhibitor keeping it present at high levels within the ECS.

CBD is a weak antagonist of CB1 receptors which contrary to agonist substances like THC, it actually blocks the receptor. This may be associated with CBD’s analgesic properties. It is also worth mentioning that CBD is a biphasic compound. Therefore its threshold between agonist and antagonist is fluid and will depend on the dosage.

CBD is also a strong negative allosteric modulator of the CB1 receptor. This means CBD modifies the way the receptor works without directly stimulating the receptor. This is most apparent when THC is present. We have known of CBD’s buffering effect on the psychoactivity of THC for some time and this is due to CBD changing how THC interacts with the CB1 receptor.

Finally CBD is a weak inverse agonist of the CBD2 receptor which means it weakens its efficiency. This very mechanism is thought to attribute to the anti-inflammatory properties of CBD. It is clear that the effects of CBD stem from both its ability to indirectly stimulate the ECS and its potential to influence other systems within the body.

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