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Endocannabinoid System

April 18, 2019

What is the Endocannabinoid System

Have you ever wondered why marijuana gets you high or how CBD oil helps with anxiety?

When you pop a capsule of CBD oil or take a puff of marijuana, the molecules that you ingest travel throughout your body and interact with biological systems that influence your health and cognition.

Much ofCannabis sativa’s effects are thanks to how certain compounds called cannabinoids interact with a system in the body that few have heard of: the endocannabinoid system, or ECS.

Read on to learn about the ECS: what it is, how it was discovered, and how phytocannabinoids and synthetic cannabinoids influence this system, resulting in a cascade of biological effects.

The Endocannabinoid System: What It Is and How It Was Discovered

The endocannabinoid system wasdiscovered thanks to research into why marijuana produces the mind-altering and pain-relieving properties that it does.

Back in the 1980s, scientists discovered that THC (tetrahydrocannabinol), a cannabinoid found in cannabis, produced its psychoactive effects through binding with receptors found throughout the brain and central nervous system.

Researchers assumed that if there were these receptors throughout our CNS that our bodies, too, would produce chemicals that bind to them. They then discovered chemicals produced within the body that do just that. These chemicals were named after plant-derived cannabinoids and were termed endocannabinoids (“endo” meaning within).  

Endocannabinoids, the receptors on which they act, and the enzymes involved in their synthesis and breakdown are collectively known as the endocannabinoid system, or ECS.

The ECS in Human Health and Disease

Ever since the discovery that humans have this complex system of chemicals and receptors throughout the cells of the central nervous system and immune system, researchers have been digging in to learn more about what it does and how it can help us understand many difficult-to-treat conditions.

From this research, scientists have discovered that theECS plays a central role in maintaining balance in the body, a process called homeostasis. By doing so, the ECS regulates our:

  • Stress response and anxiety
  • Mood
  • Inflammatory response
  • Pain sensation
  • Digestion

To understand how homeostasis works, think about stress. When you encounter a mental or physical stressor, your body will initiate a cascade of events to prepare you to deal with it. Your heartbeat will accelerate to pump more oxygenated blood to your body and your senses will sharpen.

This response readies your body to conquer the danger. If it was a lion approaching from the plains of Africa, you would be ready to fight or run. In our present day, most of the stressors that we encounter are mental. You may receive criticism from your manager or have a fight with your spouse.

For some of us, our bodies address the stressor and then return back to normal. This allows you to go on living your life in a healthy way, sleeping well and not stressing continuously. But for others, this stress response become chronic, resulting in trouble sleeping, anxiety conditions, and a reduced quality of life.

Our ECS that is partly responsible for our body’s ability to return to a normal state following stress. When it’s not functioning properly, chronic stress is one thing that might result. This is one example of maintaining homeostasis, or balance in the body. A similar balancing act is happening in response to injuries and illness with inflammation.

With many conditions credited to chronic inflammation or difficulties with mood control, learning how to target the ECS may help with many common conditions, such as anxiety and arthritis.

Clinical Endocannabinoid Deficiency and Anxiety, Pain, and More

The discovery of the ECS and how it regulates many processes has led researchers to hypothesize that many diseases might be thanks to adeficiency in the endocannabinoid system.

The theory revolves around the idea that we each have something known as endocannabinoid tone that reflects the health and function of our ECS. Our endocannabinoid tone is determined by the production, metabolism, and overall levels of our endocannabinoids and the function and abundance of our ECS receptors.

When our endocannabinoid tone is deficient, it might lead to certain types of conditions, particularly those marked by high levels of pain sensation and inflammation. Known as clinical endocannabinoid deficiency (CED), dysfunction of the ECS might be involved in:

  • Migraine
  • Irritable bowel syndrome and other digestive disorders
  • Fibromyalgia
  • Depression and other mood disorders
  • Trouble sleeping
  • PTSD (post-traumatic stress disorder)
  • Bipolar disorder
  • Glaucoma
  • Cystic fibrosis
  • Anxiety disorders

While more research is needed to determine the validity of CED and exactly what types of treatment might help to boost the health of the ECS, supplementing with cannabinoids might be one way for people with difficult-to-treat disorders to find symptomatic relief.

External Cannabinoids and the ECS

One way to target CED would be to take cannabinoids that interact with the ECS and promote optimal ECS function. This is what many people are attempting to do when they take CBD oil, and there are even pharmaceutical drugs made up of cannabinoids used to treat the symptoms of diseases like epilepsy and multiple sclerosis.

There aretwo categories of cannabinoids that are being used to target the ECS: phytocannabinoids and synthetic cannabinoids.


Phytocannabinoids, as the term “phyto” signifies, are those that come from plants. Most of the phytocannabinoids that are used and under investigation today come from theCannabis sativa plant, which includes both hemp and marijuana varieties.

The most famous phytocannabinoids are CBD (cannabidiol) and THC, although there are well over 100 others in theCannabis sativa plant. THC is the cannabinoid responsible for the psychoactive effects of cannabis, while CBD is the most thoroughly researched non-psychoactive cannabinoid.

Phytocannabinoids are traditionally consumed through the consumption of cannabis, primarily through smoking the flower, but sometimes through products that are eaten. In more recent years, pharmaceutical companies have been extracting THC and CBD from the cannabis plant and using them to treat disorders like cancer pain, epilepsy, and multiple sclerosis.

Synthetic Cannabinoids

While some pharmaceutical companies are deducing how natural phytocannabinoids can result in beneficial health effects, others are hard at work formulating synthetic (man-made) cannabinoids in the lab.

Why produce synthetic cannabinoids when there are plenty of endocannabinoids and phytocannabinoids? There are a few reasons for this, including:

  • Novel cannabinoids that may have unique benefits for health
  • Cannabinoids with fewer side effects and drug interactions
  • New cannabinoids that are more easily patented, resulting in bigger profits for the pharmaceutical companies.  

As it stands presently, phytocannabinoids are at the forefront of most of the pharmaceutical research and consumer use.

How Phytocannabinoids Interact with the ECS

When you take external cannabinoids, a cascade of events occurs. The molecules that you ingest are distributed throughout your body, where they bind with receptors and influence your biology. Much of phytocannabinoid influence on human health and wellbeing comes from their interaction with the ECS.

THC and the ECS

THC is well-known for its effects, ranging from altered cognition and drowsiness to pain relief. It is howTHC interacts with the ECS that is to thank for these effects.  

THC has a chemical structure very similar to anandamide, one of the primary endocannabinoids. Anandamide influences attention, focus, memory, learning, coordination, time perception, and pleasure. When you consume THC, it floods the ECS and displaces anandamide at receptor binding sites, impacting the mental and physical effects of anandamide.

The endocannabinoid system has two primary receptor types, CB1 receptors and CB2 receptors. The CB1 receptors are found primarily throughout the brain and the spinal cord, with most of the CB2 receptors found throughout immune system cells. 

THC has a strong affinity for CB1 receptors thanks to its structural similarity to anandamide. When it binds to CB1 receptors in the place of anandamide, you can experience the quintessential “high” experience, such as decreased reaction time and impaired memory and focus. It can also instill feelings of pleasure, calm, relaxation, and reduced pain.

CBD and the ECS

Unlike THC, CBD has very little binding affinity for either CB1 or CB2 receptors. What this means is that CBD does not bind directly to the receptors of the ECS, but ratherinfluences it in other ways. CBD is believed to enhance ECS tone, which, as discussed earlier, is the health and function of the ECS.

One of the ways in which CBD interacts with the ECS is through enhancing the effects of endocannabinoids. For instance, when you take CBD, your circulating levels of the endocannabinoid anandamide increase thanks to CBD inhibiting the reuptake of anandamide in the body (this is how the body recycles anandamide). Additionally, CBD inhibits the enzyme fatty acid amide hydrolase (FAAH), which is responsible for the breakdown of endocannabinoids.

Another way that CBD interacts with the ECS is as aCB1 receptor antagonist. This means that taking CBD blocks the binding ability of other cannabinoids to the CB1 receptor. It is through this effect that CBD may help those with central nervous system and peripheral disorders like Parkinson’s Disease.  

Learn more about THC vs CBD

Final Thoughts

It’s hard to believe that just a few decades ago we had no idea that there was a vast system of receptors and chemicals influencing our mental and physical health. With the discovery of the endocannabinoid system, we have started on a new path towards understanding, and treating, many difficult-to-treat conditions.

Phytocannabinoids like CBD and THC are two of the promising compounds already in use to target the health and function of the ECS. Over the next handful of years, we will no doubt see further research into how we can use cannabinoids to boost our health and wellbeing.  

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