What is the Endocannabinoid System?

Humans have been using cannabis for thousands of years. However, scientists have only recently started to truly understand how this plant affects our mind and body at the molecular level. It all began when tetrahydrocannabinol (THC)—the compound responsible for the euphoric high of cannabis—was first identified in 1942

Later, we learned how THC interacts with the brain when researchers discovered cannabinoid receptors. Scientists were puzzled when they realized that these were some of the most abundant neurotransmitter receptors found in the brain. This realization was soon followed by the discovery of the endocannabinoid system when the first endogenous cannabinoid, anandamide, was identified in the early 1990s. 

So what is the endocannabinoid system (ECS)?

This complex system was named for its association with the cannabis plant, but the ECS does much more than get you high. We produce our own cannabinoid compounds (endocannabinoids) that play an important biological role by maintaining balance or homeostasis in the body.

Keep reading to learn how the ECS achieves this important goal. We’ll also discuss how external cannabinoids, like THC and CBD, interact with your body’s own cannabinoid receptors.

What is the endocannabinoid system?

The endocannabinoid system is responsible for maintaining your body in a state of optimal homeostasis. In other words, the ECS works to keep your body in a stable condition where everything is working at its best, despite what might be going on outside you.

For example, your ECS aims to keep your heart rate steady and your body temperature within a set range, no matter what the temperature is outside or if you’re working out. If the outside environment forces your body to react, such as by getting hot when you’re exercising in a hot room, your ECS helps regulate the process that makes you sweat so you can cool back down. Your body is at its healthiest when it’s in a state of equilibrium, so the ECS works with the various systems in your body to maintain this equilibrium.

Three main elements comprise the endocannabinoid system:

  • Endocannabinoids: Endocannabinoids are similar to the chemical compounds found in cannabis, such as CBD and THC, which are sometimes referred to as phytocannabinoids, or plant cannabinoids. The prefix “endo” in endocannabinoids stands for endogenous, referring to the fact that these cannabinoids are internally produced by your body. Researchers have identified two main endocannabinoids in the ECS: anandamide and 2-AG.
  • Cannabinoid receptors: Cannabinoid receptors are located on the surface of cells throughout your nervous system and the rest of your body. Endocannabinoids, as well as external cannabinoids you ingest, can bind to these receptors, allowing them to communicate with various systems in your body and reset the equilibrium where needed. The two main types of cannabinoid receptors are CB1 and CB2 receptors.
  • Enzymes: After the endocannabinoids have bonded to the cannabinoid receptors and served their purpose, enzymes in your ECS work to break them down, preventing them from overcorrecting. Just as there are two endocannabinoids, there are two major enzymes to break them down. FAAH enzymes break down anandamide endocannabinoids, while MAGL enzymes break down 2-AG endocannabinoids.

All of these elements work together to help your endocannabinoid system maintain a state of homeostasis in your body.

What functions does the endocannabinoid system regulate?

Above, we used an example of overheating while working out, but many biological functions benefit from operating within a healthy range. The endocannabinoid system can help regulate all of these biological functions, including your:

  • Appetite and digestion
  • Temperature
  • Immune function
  • Inflammation
  • Motor control
  • Mood
  • Memory
  • Sleep
  • Pain and pleasure response

The ECS is able to regulate these functions through its communication with the nervous system, digestive system, and immune system—by way of the cannabinoid receptors. Although others exist, to date researchers have focused mainly on two cannabinoid receptors:

  • CB1 receptors reside in your central nervous system, which consists of your brain and the nerves in your spinal cord.
  • CB2 receptors reside in your peripheral nervous system, which consists of the nerves located throughout the rest of your body (enabling your brain to communicate with these areas), as well as your digestive and immune systems.

Because cannabinoid receptors are located throughout your body, your ECS is able to act with precision whenever it addresses an issue of imbalance in one of your bodily systems. It can pinpoint an area with inflammation and target that issue specifically, rather than affecting other systems and throwing more things out of whack.

How does the endocannabinoid system work?

We know that the ECS is important for maintaining homeostasis throughout the body. But how does it actually work? Researchers are still working to uncover the exact mechanisms used by the ECS. However, scientists have started to shed some light on the subject.

The endocannabinoid system regulates inflammation

One example is inflammation. Inflammation is a crucial response launched by the immune system to help the body fight unwanted invaders like harmful bacteria or viruses. It’s also an important step in the process of healing an injury by helping to control bleeding and prevent infection.

But while acute inflammation is an important defense mechanism, the process can sometimes go awry. If left unchecked, inflammation becomes chronic and can potentially cause many major diseases.   

In recent years, the ECS has emerged as an important regulator that helps keep inflammation in check. The most recent research shows that the body produces endocannabinoids when immune cells are activated. This helps regulate the immune response by acting as an anti-inflammatory and decreasing inflammation. The ECS ensures that the inflammatory response does its job but doesn’t get out of hand.

The Endocannabinoid System Regulates Brain Activity

The ECS is also very active in the brain and plays a key role in regulating neuronal activity. The human brain is a densely packed mass of interconnected neurons that are in constant communication with one another. 

When a neuron receives a signal from a neighboring neuron, it initiates an action potential or electrochemical signal. This signal travels through the neuron and causes the release of neurotransmitters which act as messenger molecules to carry the signal to another nearby neuron. 

Neurons don’t like to be overloaded with too many signals, but the ECS again helps keep this process in balance. Overstimulated neurons can release endocannabinoids as retrograde neurotransmitters. This means they travel backward from the target neuron towards the source of the signal. When endocannabinoids bind to CB1 receptors at the signal source, they prevent additional signals from being released. This is one reason why the ECS is thought to play a role in regulating neuronal activity in seizure disorders.

How do CBD and THC affect the endocannabinoid system?

Thanks to our body’s endocannabinoid system, natural cannabinoids from the cannabis plant, such as CBD and THC, can also bind to your cannabinoid receptors and affect your body. However, these two cannabinoids interact differently with your body’s endocannabinoid system.


THC binds to both CB1 and CB2 receptors. It’s often compared to the endocannabinoid anandamide which binds CB1 receptors in the brain and is responsible for the “runner’s high” phenomenon that we feel after intense exercise. 

However, THC binds more strongly to cannabinoid receptors and is more resistant to enzymatic breakdown. As a result, THC causes a much more intoxicating experience, or high, than our natural anandamide. The short term effects of THC can include:

  • Relaxation
  • Sedation
  • Elation
  • Memory impairment
  • Hunger
  • Increased heart rate
  • Dry mouth
  • Anxiety or paranoia
  • Slowed perception of time
  • Laughter

Unfortunately, research looking at the medicinal effects of THC has stagnated throughout the last century due to legal restrictions. Despite this, THC has several well documented therapeutic effects. THC may help treat a large number of symptoms including:


Because THC is intoxicating and illegal in many areas of the world, CBD has emerged as a promising drug candidate for researchers. It possesses many useful therapeutic properties by stimulating the ECS, but, unlike THC, CBD doesn’t get you high. 

That’s because CBD interacts with the ECS differently than THC. It only binds weakly to CB1 and CB2 receptors. And when it does, CBD actually acts as an antagonist. Sometimes called blockers, antagonists bind to receptors and dampen their signals. This explains why CBD can counteract the effects of THC intoxication.

CBD also affects your ECS by inhibiting the FAAH enzyme, which breaks down anandamide. Anandamide produces a calming effect, so by blocking the FAAH enzyme that breaks it down, CBD can be helpful in treating anxiety disorders.

Homeostasis plays an important role in our overall health. Since external cannabinoids like CBD can bond to our cannabinoid receptors just as well as the endocannabinoids our bodies naturally produce, researchers are finding that CBD products can have wide-ranging therapeutic benefits for various health issues, including:

  • Anxiety: CBD interacts with a wide range of receptors aside from CB1 and CB2, including several receptors known to regulate anxiety-related behavior.
  • Insomnia: The ECS plays a role in regulating our sleep patterns and CBD has shown great potential as a treatment for insomnia. 
  • Cancer: Preliminary research demonstrates CBD’s ability to slow tumor growth and alleviate the negative side effects of cancer treatments like nausea and pain.
  • Muscle spasms and pain: CBD can also help control difficult to treat, chronic pain as in the case of arthritis and multiple sclerosis.
  • Inflammation: As we discussed, the ECS is very active in regulating the inflammatory process. As a result, ECS stimulation by CBD can help keep inflammation in check.

What is endocannabinoid deficiency?

Endocannabinoid deficiency is a relatively new area of research, but the implications are far-reaching. It theorizes that major diseases involving systems regulated by the ECS could be, at their core, caused by a lack of endocannabinoids.

Someone with an endocannabinoid deficiency would have chronically low levels of endocannabinoids including anandamide and 2-AG, similar to how depression is thought to be caused by low levels of serotonin. Low cannabinoid levels could be caused by genetic or lifestyle factors and would result in a reduced pain threshold as well as a digestive, mood, and sleep issues.

First proposed by the prominent psychopharmacology and cannabinoid researcher Dr. Ethan Russo, clinical endocannabinoid deficiency (CED) seeks to explain why disorders like migraine, fibromyalgia, irritable bowel syndrome can be successfully treated with cannabis.  

According to Russo, these disorders have the most evidence for being caused by CED. They all share several characteristics including:

  • Symptoms of enhanced sensitivity to pain
  • Diagnosed by subjective patient symptoms as opposed to objective lab tests or medical imaging
  •  Accompanied by increased anxiety and depression
  • Comorbidity (for example, the far majority of fibromyalgia patients also suffer from migraines

Indeed, some studies have found that migraine sufferers have lowered levels of anandamide. Other disorders could fall under the CED umbrella as well. For example, PTSD is associated with abnormal anandamide signaling in the brain. More research is needed, but CED highlights the importance of the ECS in human health.

Additional Resources

Learn more about CBD at the links below.