Endocannabinoid system: What it is, how it works, and more

Every person has an endocannabinoid system (ECS), which is a complex network of receptors, lipids, and enzymes. The ECS plays a valuable role in balancing many of your bodily functions. It also affects how you experience cannabis.

Discovered in the late 1980s, the ECS helps regulate your sleep, appetite, immune function, and much more. When the endocannabinoid system is out of balance, it can negatively impact important processes in the body.

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How the endocannabinoid system works

The endocannabinoid system spans the entire body. It’s mainly found in the nervous system, immune system, and digestive system, but is also present in the heart, eyes, respiratory tract, and beyond.

The ECS is made up of three main parts: endocannabinoids, receptors, and enzymes.

Endocannabinoids

Most of us are familiar with the cannabinoids found in cannabis, like tetrahydrocannabinol (THC) and cannabidiol (CBD). Both interact with the ECS. Some cannabinoids, like THC, are intoxicating; others, like CBD, are not.

But the body also makes its own cannabinoids, known as endocannabinoids.

Endocannabinoids attach to receptors in our body’s immune cells. They act as messengers that send signals to and from different body systems. They do this by binding to the body’s cannabinoid receptors, which produce chemical reactions that affect bodily functions like inflammation, stress, or sleep.

These endocannabinoids can be found throughout the nervous system, up and down the spine, in every brain cell, and even in the skin.

Researchers have identified two important endocannabinoids in the body:

Anandamide: Discovered in the 1990s, anandamide is named after the Sanskrit word “ananda,” meaning eternal happiness. Anandamide interacts with the body similarly to THC, and affects your serotonin levels. It’s the chemical responsible for the “runner’s high” you may experience after exercise.
2-arachidonoylglycerol (2-AG): This endocannabinoid can be found in the central nervous system. It has pain-relieving and anti-inflammatory effects. 2-AG also impacts your appetite, immune system function, and synaptic activity (the communication between the brain’s neurons).

However, research on endocannabinoids is relatively new, and more studies are needed to fully understand their role in the body.

Cannabinoid receptors

Cannabinoid receptors are found in almost every organ of the body. When activated by cannabinoids, they play a role in homeostasis, which means the body’s internal environment is well balanced and able to adapt to external changes.

Both endocannabinoids and the cannabinoids found in cannabis activate these receptors to improve how the body functions. For example, anandamide activates receptors in the brain that balance mood and increase feelings of reward.

There are two kinds of cannabinoid receptors:

CB1 receptors: These are mainly in the brain and central nervous system, but can also be found in many other organs, glands, and connective tissues. Both THC and anandamide interact with CB1 receptors.
CB2 receptors: These are found mainly in the immune and nervous systems but can also be found in the brain. 2-AG mostly acts on CB2 receptors, though THC does as well.

Enzymes

The endocannabinoid system’s enzymes break down and help the body process cannabinoids, including endocannabinoids and those found in cannabis.

The two main ECS enzymes are:

Fatty acid amide hydrolase, which breaks down anandamide and THC.
Monoacylglycerol lipase, which breaks down 2-AG.

What does the endocannabinoid system do?

The ECS regulates many essential functions of the body, including:

Appetite
Brain development
Emotional processing
Immune system
Inflammatory response
Learning and memory
Mood
Pain sensation
Reproduction
Reward perception
Sleep
The pleasurable effects of exercise

Phytocannabinoids and the endocannabinoid system

While endocannabinoids are produced in the body, phytocannabinoids come from plants. The cannabis plant contains approximately 150 unique cannabinoids, including THC, CBD, and more.

THC

THC is the dominant cannabinoid in marijuana. It’s an intoxicating phytocannabinoid that can be used to:

Boost appetite
Calm an overactive bladder
Ease nausea and vomiting
Reduce inflammation
Relieve pain
Treat muscle spasticity

CBD

Like THC, CBD acts as an anti-inflammatory. It can also help stabilize mood and reduce muscle spasms.

CBD is commonly used to help with health issues such as:

Anxiety
Chronic pain
Depression
Epilepsy
Multiple sclerosis

Other phytocannabinoids

THC and CBD are the most abundant phytocannabinoids in cannabis. But many more also interact with the endocannabinoid system to produce their own unique effects, including:

Foods that contain phytocannabinoids

While cannabinoids are mostly associated with cannabis, other plants contain cannabinoids, as well — in much smaller amounts. But you can find cannabinoids in foods such as:

Black pepper
Broccoli
Chocolate
Cinnamon
Kale
Kava

In fact, black pepper is a common remedy for THC over intoxication. That’s because black pepper interacts with the endocannabinoid system to reduce sensitivity to THC.

How phytocannabinoids interact with cannabinoid receptors

Each cannabinoid interacts with the ECS in a different way. They may activate CB1 receptors, CB2 receptors, or both — or through other mechanisms altogether.

Cannabinoids also differ in how well they can attach to receptors, which affects their potency — and the benefits they provide. Depending on the cannabinoid used, it may work as:

Anti-anxiety
Antidepressant
Anti-inflammatory
Anti-nausea
Appetite stimulation
Epilepsy treatment
Mood stabilization
Multiple sclerosis treatment
Pain relief

What is clinical endocannabinoid deficiency (CED)?

Clinical endocannabinoid deficiency (CED) is a theory created by Dr. Ethan Russo. It states that many common health conditions can be linked to an endocannabinoid system imbalance, whether caused by a lack of endocannabinoids within the body, or problems with cannabinoid receptors.

It’s thought that this imbalance may result from an injury, an infection, a genetic dysfunction, or an event that triggers long-term inflammation. Dr. Russo’s research has connected certain health conditions with CED, including fibromyalgia, migraines, and irritable bowel disease (IBD).

Dravet syndrome and Lennox-Gastaut syndrome (two types of epilepsy) may be caused by a missing genetic coding for a specific endocannabinoid that helps regulate calcium and sodium ions.

Can long-term cannabis use affect the ECS?

There isn’t much research around the impact of long-term cannabis use on the ECS. It’s best to use cannabis as directed by your physician to avoid over intoxication.

Long-term THC use may lead to tolerance, where users need to keep increasing their dosage to achieve the same desired effects. This might mean that with repeated use, the endocannabinoid receptors activated by THC become less sensitive.

The bottom line: The endocannabinoid system helps keep your body in check

The ECS helps regulate processes like sleep, appetite, pain sensation, and mood, so that your body can operate at its fullest potential. So it’s possible that if the ECS isn’t functioning properly it may increase your risk of developing certain health conditions.

Phytocannabinoids like THC and CBD interact with the ECS to offer a number of health benefits. However, more research on the long-term effects of cannabis on the ECS is needed.

Consider speaking with a cannabis-knowledgeable healthcare professional, like those at Leafwell, to learn more about the ECS and receive personalized guidance on using medical marijuana to address your individual health concerns.

Frequently asked questions

Here are the answers to some commonly asked questions about the endocannabinoid system.

Is the endocannabinoid system real?

Yes, the endocannabinoid system is a real functioning system in your body. It helps regulate numerous bodily functions, including appetite, immune function, mood, pain perception, sleep, and more.

In fact, researchers are studying the ECS to make more effective medications that fight disease.

Do our bodies produce cannabinoids?

Our bodies naturally produce endocannabinoids, a type of cannabinoids made within the ECS. These cannabinoids interact with receptors throughout the body to help regulate important bodily functions and keep things running smoothly.

How does CBD affect the endocannabinoid system?

CBD helps increase endocannabinoid levels in the body. This allows them to have a larger impact on regulating things like pain and mood.

How does the endocannabinoid system affect the brain?

The ECS balances certain brain processes like emotional processing, memory, and learning. Researchers have also found that cannabinoid receptors regulate mental health and may play a role in post-traumatic stress disorder (PTSD).

Resources

2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor.
https://www.pnas.org/doi/10.1073/pnas.061029898
An introduction to the endogenous cannabinoid system.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4789136/
Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5877694/
Clinical endocannabinoid deficiency reconsidered: Current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5576607/
Marijuana may boost, rather than dull, the elderly brain.
https://www.scientificamerican.com/article/marijuana-may-boost-rather-than-dull-the-elderly-brain/
Polymodal activation of the endocannabinoid system in the extended amygdala.
https://pubmed.ncbi.nlm.nih.gov/22057189/
Recent advances in endocannabinoid system targeting for improved specificity: Strategic approaches to targeted drug delivery. https://pubmed.ncbi.nlm.nih.gov/36362014/
Review of the neurological benefits of phytocannabinoids.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5938896/
The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2219532/
The endocannabinoid system and the brain. https://www.researchgate.net/publication/229163258_The_Endocannabinoid_System_and_the_Brain
The endocannabinoid system as a modulator of exercise benefits in mental health. https://pmc.ncbi.nlm.nih.gov/articles/PMC8719298/
The endocannabinoid system of animals.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6770351/
Therapeutic effects of cannabis and cannabinoids.
https://www.ncbi.nlm.nih.gov/books/NBK425767/

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