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What is the endocannabinoid system?

Many people have never heard of the endocannabinoid system, even though it’s been referred to as the most important physiological system involved in establishing and maintaining human health. The endocannabinoid system is a communication system within the body of many animals, including mammals, reptiles, birds and fish, with the primary function of keeping homeostasis. What is homeostasis, you ask? It’s maintaining balance where the internal environment stays stable regardless of external variables. For example, if your blood pressure is too high, the heart should slow down; if it is too low, the heart should speed up.

Everyone has an endocannabinoid system that is active within the body at all times; this means it’s active with or without the presence of cannabis. Because your endocannabinoid system is always present, you can boost the ECS function without introducing cannabis into the body. A few ways to perk up your endocannabinoid system include eating dark chocolate, exercise, drinking coffee, and having sex. Imagine how great you’ll feel if you do all of the above on top of incorporating cannabis into your routine – health, here we come!

Research has shown that the endocannabinoid system is responsible for regulating a boat load of super vital functions within the body, including:

  • Pain
  • Mood
  • Energy
  • Anxiety
  • Sleep
  • Liver function
  • Stress
  • Inflammation
  • Metabolism
  • Learning and memory
  • Motor control
  • Consciousness

The endocannabinoid system also works in retrograde. No, we don’t mean mercury retrograde when everything in your life gets wonky, and you can’t blame it on the moon. The endocannabinoid system was the first system to be discovered that works in this way. In a nutshell, the neurotransmitters (chemical messengers) are moving in the opposite direction of the other neurotransmitters in the body. Instead of neurotransmitters moving through the synapses to the brain to fire a response, the endocannabinoid system will send response signals from the brain that attach to the neurons and go through the cycle.

How does it work?

The endocannabinoid system works by cannabinoids attaching to receptors in the body. There are two different types of receptors called CB1 and CB2. If you were to look at an endocannabinoid system diagram, you would see how the neurons and receptors interact with each other and the retrograde cycle. Let’s break these CB1 and CB2 receptors down a little more.

Endocannabinoid Receptors

CB1 receptors can primarily be found in the central nervous system and the brain working hard at regulating brain functions. When cannabinoids attach to CB1 receptors, they are typically associated with motor functions, coordination and appetite. By activating the CB1 receptors, your body can lower blood sugar, anxiety, depression, and inflammation, among other mind-blowing benefits.

CB2 receptors can be found all over the body, including the bones and liver, and are in the peripheral nervous system on cells associated with immune response. When cannabinoids attach to CB2 receptors, they are associated with pain management and inflammation.


The word endocannabinoid is short for endogenous cannabinoid. These molecules are cannabinoids manufactured by the body. Typical levels of endocannabinoids in the body are not known since the body produces them as and when needed.

It is endocannabinoids that bind and activate cannabinoid receptors, and they are of two types.

  • 2 – arachidonoylglyerol (2-AG)
  • Anandamide (AEA)

Anandamide connects with CB1 receptors, while 2-AG connects with CB2 connectors. Both of these endocannabinoids are made up of fatty molecules, and they are typically found on the cell membrane.

Metabolic Enzymes

As earlier mentioned, the body doesn’t keep endocannabinoids in reserve; it just produces them when needed. So what happens to them when they have been used? Once endocannabinoids have restored the homeostatic balance, metabolic hormones destroy it.

The fact that they are only produced when needed distinguishes endocannabinoids from other molecular signals in the body. Common neurotransmitters and hormones either remain in the body long after they have accomplished their purpose or the body manufactures and keeps them in stock to be used when the need arises.

A different hormone synthesizes each of the two endocannabinoids;

  • Fatty acid amide hydrolase (FAAH). This one breaks down Anandamide (AEA)
  • Monoacylglycerol acid lipase (MAGL) typically breaks down 2 – arachidonoylglyerol (2-AG)
Endocannabinoid System Diagram

Endocannabinoids vs Cannabinoids

There are little messengers made up of chemicals within the endocannabinoid system, and these are called cannabinoids. These cannabinoids can be either endogenous cannabinoids or exogenous cannabinoids. These words are a mouthful, so let’s learn a bit more about them, shall we?

Endogenous cannabinoids

Endogenous cannabinoids originate inside the body. We also refer to these as endocannabinoids, hence the name of the system. Right now, experts know of two primary endocannabinoids, anandamide (AEA) and 2-arachidonoylglyerol (2-AG). Endocannabinoids are produced naturally in your body. When endocannabinoids are working their way around your body, they attach to CB1 or CB2 receptors that regulate things in your body like stress, mood, sleep, pain, and appetite. This brings us back to that state of homeostasis or balance that we talked about earlier, which is the primary function of the endocannabinoid system.

Exogenous cannabinoids

Exogenous cannabinoids originate outside of the body and are a chemical compound that can be found in the cannabis plant. There are many different types of exogenous cannabinoids, but some of the most popular ones are cannabidiol (CBD), tetrahydrocannabinol (THC) and cannabigerol (CBG). When you ingest a cannabis product, whether you smoke it, eat it, or vape, the available cannabinoids find those CB1 or CB2 receptors and get to work doing the tasks required to regulate your body’s vital functions.

With so many chemical systems in the body, there are two options once the hormones and neurotransmitters have completed their jobs. The internal systems will hold onto any excess hormones and neurotransmitters to store them for later use, or the internal systems will continually create the hormones and neurotransmitters to be available whenever they are needed. This raises the question of whether the endocannabinoid system follows suit or if it is possible to have too many cannabinoids or endocannabinoids in your system. This is noteworthy because as we circle back to homeostasis, once that balance is restored within the endocannabinoid system and the body is back to homeostasis, your metabolic enzymes destroy any leftovers. In other words, the endocannabinoid system only uses what it needs; it never stores leftovers and does not continually produce excess neurotransmitters and hormones.

Working in Retrograde

The endocannabinoid system is said to work in retrograde. Working in retrograde means that its signals move opposite other neurotransmitters in the body.

The nervous system is made up of chains of neurons. These neurons are found in every part of the body. They connect in a string to the central nervous system and ultimately to the brain. Between every two neurons, there is a tiny gap known as a synapse. The neuron that comes after the synapse is referred to as a postsynaptic neuron.

Common neurotransmitters move through synapses from the rest of the body towards the brain. Every neuron receives the signal, reacts to it (for example, if the neuron is transmitting a pain signal, it ‘feels’ the pain and passes it on to the next (postsynaptic) neuron — the more intense the pain, the more frequently the neurons fire.

The endocannabinoid signaling moves in the opposite direction, towards the pre-synaptic neuron. Let us use the pain signal as an example. When the neurons send pain signals to the brain, the brain sends endocannabinoids to bind with it. This binding keeps the neurons busy, reducing the frequency with which it sends the pain signals, when the rate at which neurons send pain signals reduces, the intensity of pain as felt by the body decreases.

How does the ECS interact with THC?

THC, or tetrahydrocannabinol, is one of the main cannabinoids found in cannabis. It’s also the compound that is responsible for the psychoactive effects that get you high. When THC enters the body, it will bind to both CB1 and CB2 receptors, just like endocannabinoids do. However, THC does prefer CB1 over CB2, which can affect the body in a number of ways, providing relief for issues like pain management or appetite stimulation.

How does the ECS interact with CBD?

CBD, or cannabidiol, is the other prominent cannabinoid found in cannabis. However, unlike THC, CBD does not provide any psychoactive effects and will not get you high nor will it cause any adverse side effects. The endocannabinoid system and CBD have an interesting relationship because CBD doesn’t attach to one receptor over the other. It will simulate both types of receptors, and some experts say that CBD limits how THC interacts with the CB1 receptors, counteracting the effects of THC on the body. CBD also binds to serotonin receptors that influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, and sleep.

The endocannabinoid system and health issues

Marijuana and hemp have been used for thousands of years to treat a wide variety of ailments and medical conditions, and sometimes it seems too good to be true – how can one herb do so much with so few adverse side effects? Some researchers believe that the root of a number of medical conditions like migraines, irritable bowel syndrome and fibromyalgia are due to something called clinical endocannabinoid deficiency. This theory questions whether individuals that suffer from certain medical conditions produce a lower level of endogenous cannabinoids than those who do not suffer from those medical conditions. This is the theory that explains why so many people are experiencing therapeutic benefits from using cannabis to manage these health conditions. Research also indicates that because the endocannabinoid system’s goal is to bring balance to the body, it can also help with medical conditions that are not directly linked to clinical endocannabinoid deficiency, like neurodegenerative disorders, cancer, and arthritis.

This is only the beginning

Solid research surrounding a primary human system can take a tremendous amount of time and dedication. However, it’s incredible what we have learned about the endocannabinoid system in only 30 years—science is basically killing it on all levels of exploration into how our biological systems engage with cannabis. With legislation becoming more progressive and millions of people around the world experiencing health benefits, we’re betting the discoveries we’ve made so far are just the tip of the iceberg. In fact, some experts believe there are more receptors and cannabinoids to be uncovered, so this, my friends, is just the beginning of the herbal revolution.


Basu, S., & Dittel, B. N. (2011, October). Unraveling the complexities of cannabinoid receptor 2 (CB2) immune regulation in health and disease. Immunologic research.

EB;, R. (2004, April 25). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinology letters.

M;, M.-R. E. P.-T. J. C. S.-C. M.-la-C. (n.d.). The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. CNS & neurological disorders drug targets.

McPartland JM;Agrawal J;Gleeson D;Heasman K;Glass M; (n.d.). Cannabinoid receptors in invertebrates. Journal of evolutionary biology.

Russo, E. B. (2016, July 1). Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis and cannabinoid research.

Zou, S., & Kumar, U. (2018, March 13). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International journal of molecular sciences.