Exploring the Endocannabinoid System

If you don’t know much about the endocannabinoid system -ECS – don’t feel bad. Even researchers have only begun to scratch the service of this incredible physiological system. 

The ECS is widespread and critical to how your body functions. It’s so vital, yet we barely ever talk about it.

Endocannabinoid signalling directly plays a role in multiple bodily functions, including pain perception, appetite, memory, and more. Even if without involving cannabis, increasing your understanding of this system can profoundly benefit your health and wellbeing.

What is the Endocannabinoid System?

The ECS serves a regulating or moderating role throughout the human body. In simpler terms, think of it as a dimmer switch that reduces physiological activity when turned on.

In more complex terms, this ancient lipid signalling system has been found in all living vertebrates and was a part of human evolution.

Within our bodies, lipids serve multiple functions, including storing energy, signalling, and acting as structural components of cell membranes.

The endocannabinoid system is composed of three primary parts: 

  • Receptors 
  • Ligands
  • Enzymes 

Later in this article, we’ll discover how cannabis plant cannabinoids essentially mimic our natural ligands to impact endocannabinoid signalling.


First, we have endocannabinoid receptors, which are like little locks that only accept specific keys. There are currently two endocannabinoid receptors under this class. Conveniently, their names are Cannabinoid-1 and Cannabinoid-2 (CB1 and CB2) receptors. 

These receptors are found all over the body, between nerve cells, on immune cells, and even inside each cell surrounding the mitochondria, also known as the powerhouse of the cell. 

endocannabinoid system

CB1 receptors are best known for how populated they are inside the central nervous system. They impact our cognition and sensations. CB2 receptors are best known for being found on immune cells. They are triggered when there is inflammation, or the body suffers an injury. 

When this happens, CB2 receptors inhibit inflammatory signalling pathways, thereby bringing things back to a non-inflammatory state, or what is formally known as homeostasis

Basically, homeostasis is your body’s default stage that lets you know that all’s good in the hood.  


Second, ligands are called endogenous cannabinoids, or endocannabinoids, which act as the keys for the specific receptor locks. 

The two major endocannabinoids studied are anandamide (the ‘bliss’ molecule) and 2-Arachidonoylglycerol (2-AG). If you’re intimidated by the names, we totally get it. Don’t worry. We’ll break it down for you.

Anandamide is released after bouts of exercise and under other specific circumstances where the body is exerted. When anandamide release is necessary, these molecules float over to CB1 receptors and produce various effects. 

For example, runner’s high is one of the most profound impacts of this endocannabinoid signaling, leading to pain-relief, appetite-promotion, and sedation. 

When 2-AG is released on-demand, these compounds target CB2 receptors found on immune cells. This endocannabinoid signalling ultimately impacts how our immune system functions.


Finally, some enzymes play a role in the building and recycling of endocannabinoids. 

Some of the enzymes play a role in endocannabinoid synthesis or creation. Others are responsible for ending the signal at cannabinoid receptors by breaking down used endocannabinoids. 

For example, 2-AG is synthesized with involvement from the enzyme diacylglycerol lipase (DAGL).

The cannabinoids found inside the cannabis plant happen to fit these cannabinoid receptors nicely. In other words, plant-made phytocannabinoids are keys that fit these locks.

Before we talk about CBD and THC, we’ll learn a bit more about what the ECS actually does.

What Does the Endocannabinoid System Do?


Similar to how nicotinic receptors detect nicotine, cannabinoid receptors detect cannabinoids. 

Both sets of receptors got their names after searching for the target of substances consumed by humans. Since scientists were aware of how the compounds affected our physiology, we knew that there had to be receptors and other physiological and biological mechanisms involved. 

On a microscopic scale, the ECS plays a role in reducing nervous system signalling. When the CB1 receptors found at nerve synapses are activated, they lead to reduced neural signaling. This function is what leads to the ‘dimmer switch’ description of the role of the ECS. 

In the immune system, the actions of CB2 receptors play a role in how our immune cells operate. Basically, the ECS can either ramp-up or settle-down the role of our immune cell protectors and fighters. 

Finally, we also know that mitochondrial cannabinoid receptors play a role in the energy balance of cells. In other words, these receptors regulate the functioning of our cellular power plants inside each cell.

These three basic mechanisms are the best-studied aspects of how our ECS functions. At a human level, we know these effects combine to impact a variety of everyday functions. What sort of physiological processes is the ECS involved in? 

Here’s the very long list:

  • Immune function
  • Appetite
  • Metabolism and energy
  • Homeostasis
  • Inflammation
  • Central nervous system development
  • Bone development and bone density
  • Synaptic plasticity and learning
  • Pain
  • Reproduction
  • Psychiatric disease
  • Wake/sleep cycles
  • Regulation of stress
  • Regulation of emotional state/mood
  • Psychomotor function

Sadly, this system does not always function correctly, and the dysfunction of the ECS can have intense impacts that are worth noting. Specifically, when the ECS doesn’t work properly, it can lead to:

  • Pain
  • Psychiatric disorders
  • Neurodegenerative diseases
  • And more

To help promote the normal functioning of your endocannabinoid system, we have a few clues.

We know that moderate-intensity exercise promotes the release of anandamide, leading to numerous health benefits. The key factor here is duration, as it seems that exercising with a moderate intensity over longer periods is the best for the endocannabinoid system. 

More specifically, aim for exercise that is over 30 minutes long.

Additionally, since the ECS is a lipid signalling system, eating lots of healthy fats can help ensure your body has the building block pieces it needs.

Finally, getting a proper amount of sleep is something that we should all strive to obtain. 

How do CBD and THC Affect the ECS?

While CBD and THC are both cannabinoids produced by cannabis plants, they are each very unique, just like terpenes. They fall under the same class of compounds and are both lipids, but after that is when their differences genuinely come to light.

How each impacts the human ECS varies greatly and is a fascinating area to explore. The role of THC is more clear and well-understood, while the functions of CBD are more complex. 

As we go through each, you’ll see why.

Put simply, THC is structurally similar to anandamide and serves a similar role in our ECS. Like anandamide, THC targets CB1 receptors in the brain and throughout the body to produce its effects. 

When we mentioned the effects of a runner’s high before, astute readers may have noticed how the impacts are similar with applied doses of THC. But, without having to exercise, the application of THC is associated with pain-reduction, appetite-stimulation, and sleep-promotion. 

An important concept to learn when it comes to ingesting THC is the term biphasic. This term describes how a small amount of one substance can reduce a symptom, while a large dose will do the opposite. 

Shifting our focus to the other primary cannabis compound of interest, CBD, the story changes. CBD is more akin to 2-AG and impacts CB2 more than CB1 receptors. 

However, CBD is not identical to 2-AG and does not directly fit the CB2 lock. Instead, it impacts CB2 functioning indirectly. Nonetheless, the widespread presence of CB2 receptors leads to dramatic impacts of CBD on our health and wellbeing. 

As opposed to THC, CBD does not typically produce any psychoactive effect or cognitive impairment. The role of CBD at CB2 receptors and other targets could support the following effects:

The Endocannabinoid System – A Truly Essential System

Congrats on making it to the end of this guide to the endocannabinoid system or ECS! While this guide contains a lot of helpful information, there is still a lot to learn and so much more for researchers to discover. 

Nonetheless, what we already know about the ECS is absolutely fascinating. Whether you consume cannabis or not, knowing about this system is good for your ability to maintain good health and wellbeing. 

Sirona Pharma

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