Cannabis Science - Cannabis Studies
March 5, 2019

Intro to The Endocannabinoid System

Mel Perron
6 min

Understanding how the endocannabinoid system was discovered and what it does in our bodies is an important first step to understanding how cannabis can best work with our bodies to reduce the side effect of ailments, and maintain a healthy life. Without the endocannabinoid system, we would be unable to experience the medical benefits of cannabis.

Discovering the Endocannabinoid System

The endocannabinoid system was named after the plant which led to its discovery, cannabis. In 1964 the Israeli scientist Raphael Mechoulam began extensive research into cannabis. Mechoulam and his team isolated THC, the most abundant cannabinoid in cannabis, which is also responsible for its intoxicating and sedating effects. This discovery opened the door for a lot of questions; how does THC affect the body? Are their more cannabinoids? If so, what are the effects of these cannabinoids?

Further research began as Mechoulam and his team discovered and isolated hundreds of different cannabinoids including CBD, the most famous and second most abundant cannabinoid that holds huge therapeutic potential.

Exogenous Cannabinoids

THC, CBD, and the hundreds of other cannabinoids discovered are what we call exogenous plant cannabinoids. This means cannabinoids that are found in a plant.

Following the discovery of exogenous plant cannabinoids (again, cannabinoids within plants), research turned inward to isolate endogenous cannabinoids otherwise known as endocannabinoids. The prefix “endo” means “in”, adding the prefix to cannabinoid creates the term endocannabinoid or internal cannabinoids.


Discovering endocannabinoids was a huge step, this meant that there was an omnipresent system in place to utilize these chemicals within our bodies. Our bodies naturally create two endocannabinoids; anandamide and 2-Arachidonoylglycerol or 2-AG for short.

Agonists and Antagonists

Cannabinoids can behave in two ways; as an antagonist or as an agonist.


When a cannabinoid binds to a receptor and stops a physiological change or action it is called an antagonist.


When a cannabinoid binds to a receptor and starts a physiological change or action it is called an agonist.

How does cannabis help with ailments?

Cannabis and its molecules have the ability to both upregulate and downregulate certain bodily functions, meaning THC and CBD can be both agonists and antagonists. This ability allows cannabis to help with a wide variety of ailments and be used in diverse ways.

The Endocannabinoid System

The endocannabinoid system is a universal system of internal regulation, cellular communication, and homeostasis; It plays a very important role in establishing and maintaining human health. The endocannabinoid system is present in humans, animals, and plants alike, only missing from insects. It is believed that this system appeared about 500 million years ago and kept on evolving to what we have today.

The Endocannabinoid system consists of three major components:

  • The receptors: cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).
  • The endocannabinoids: anandamide and 2-AG that interact with these receptors.
  • The enzymes: Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL) that are responsible for the synthesis of the endocannabinoids.

The endocannabinoids system has a hand in most of the bodies basic functions, controlling your sleeping and eating cycles, as well as, memory, relaxation and your bodies protection responses.

All of the following systems are influenced and in part regulated by the endocannabinoid system:

  • Stress
  • Emotion
  • Memory
  • Cognition
  • Sleep
  • Digestion
  • Inflammation
  • Thermoregulation
  • Neural development
  • Neuroprotection
  • Movement
  • Psychomotor behavior
  • Pain
  • Cardiovascular and immune function
  • Metabolism
  • Appetite regulation

The Lock and Key Analogy

Breaking down the complex systems of our bodies is no easy task, many educators have turned to “the lock and key” as an easy analogy to help summarise the relationship between cannabinoids and the receptors of the endocannabinoid system.

CB1 and CB2 Receptors are the Locks

CB1 and CB2 receptors are located in the membrane of a cell. In order to experience the effects of the cannabinoid, they must “fit into” either the CB1 receptor or the CB2 receptor.

Cannabinoids are the Keys

Both endogenous and exogenous cannabinoids (cannabinoids found in our bodies or plant cannabinoids like THC and CBD) can interact with these receptors like a key fitting into a lock.

CB1 Receptors and Tetrahydrocannabinol (THC)

While our endocannabinoid receptors naturally bind with our own endocannabinoids (like amandine and 2-AG), cannabinoids such as THC mimic these endocannabinoids so closely that they bind to these receptors. This relationship causes a variety of medicinal benefits, as well as, the intoxication commonly associated with THC. THC binds with the CB1 receptor, producing strong analgesic effects and more.

Location of CB1 Receptors in our Bodies

CB1 receptors are primarily located throughout your nervous system. The locations of the cannabinoid receptors in our bodies are what allows the endocannabinoid system to so heavily influence our bodies regulatory functions. This biological trait allows cannabis to potentially provide relief for all areas of the body.

CB2 Receptors and Cannabidiol

CBD, the non-intoxicating cannabinoid within cannabis, binds with the CB2 receptor in our body. Oddly enough, the absorption of CBD through the CB2 receptor has a huge role to play in the absorption of THC. Consuming a product that has CBD and THC together increases and drastically changes a cannabis experience compared to consuming a product that contains THC or CBD alone.

Location of CB2 Receptors in our Bodies

CB2 receptors are primarily located within your immune system, the location of these receptors is a major factor in cannabis’s ability to affect your immune system responses. Immune responses include inflammation from ailments such as crones and arthritis. These attributes of CBD and CB2 receptors have pushed CBD to the forefront of medicinal studies for the wide array of ailments and symptoms that can be naturally relieved with zero intoxication.

Summarizing the endocannabinoid system

When you consume cannabis in any of its forms (oil, smoking, vaporization) you are introducing cannabinoids into your system. Cannabinoids like THC and CBD bind to the receptors of the endocannabinoid systems throughout your body, influencing many different bodily functions. The relationship between cannabinoids and your endocannabinoid system is the reason humans and animals alike experience the effects of cannabis. Understanding the endocannabinoid system is a vital part of utilizing cannabis to its fullest potential as a medicine.

New Endocannabinoid Research

With attitudes towards cannabis relaxing, new research is happening within the cannabis industry all the time; recently science has turned to terpenes, the oily substances produced by plants that control aroma and flavor. Scientists are delving into the influence of different terpenes on the endocannabinoid system to establish relationships and interactions. For example, caryophyllene, a terpene that is commonly found within cannabis has been found to bind to the CB2 receptor and influence the endocannabinoid system; while other terpenes like myrcene allow for an increased absorption rate of cannabinoids through your blood-brain barrier which allows you to potentially require less cannabis while maximizing benefits.

The endocannabinoid system is our bodies natural ever-present system that maintains our bodies sense of balance and well being. Ailments, stress, and sickness can interfere with our bodies ability to regulate its normal functions, throwing us off balance and causing many people to turn to cannabis as a last resort. The endocannabinoid system is the backbone of cannabis’s ability to help restore balance, health and quality of life for many patients.

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