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The Endocannabinoid System


The Endocannabinoid System (ECS) is a complex biological messaging system within the body that functions to maintain homeostasis across a variety of systems.

It is comprised of three main components:  A.) lipid-bases neurotransmitters called endocannabinoids, B.) receptors located throughout the brain and central/peripheral nervous systems, and C.) the enzymes that break them down.

The role of the ECS is to maintain homeostasis in the body by modulating and maintaining various physiological functions, such as: pain, inflammation, appetite, muscle control, energy balance, metabolism, sleep, stress, and mood.

The reason that cannabis and hemp produce such a range of proposed healing effects on the human body is because of their ability to interact with our body’s ECS.

Let’s dive in and take a closer look!

Table of Contents

Brief History of the ECS

Role of the ECS

What makes up the ECS

Phyto cannabinoids and the Endocannabinoid System – CBD & THC

In Summary


Brief History of the ECS:

If you have ever wondered why the Endocannabinoid System seems to be named after Cannabis, it’s an interesting story. The truth is that scientists essentially stumbled upon the human ECS while on a quest to understand how Cannabis compounds (namely THC) interacted and affected the body.

Though scientists were aware of both CBD and THC in the 1940’s, it wasn’t until 1988 that solid evidence was presented to show the existence of specific cannabinoid receptors in the mammalian body – subsequently leading to the discovery of the CB1 and CB2 receptors. They just so happened to find, as well, that these receptors were the most abundant type of neurotransmitter in the brain. With the discovery of these novel and prevalent receptors, scientists knew the ECS was likely to be an important piece to the puzzle of the body [10]. Shortly after, we saw discovery of the two most prevalent endo-cannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG), as well as other lesser known constituents [09].



Role of the ECS:

The endocannabinoid system is involved in an array of both central neural activities, as well as physiological and pathological conditions in the PNS including: [11]

    • Appetite
    • Learning and memory
    • Anxiety
    • Depression,
    • Schizophrenia
    • Stroke
    • Multiple sclerosis
    • Neurodegeneration
    • Epilepsy
    • Addiction
    • Pain
    • Metabolism
    • Cardiovascular and reproductive functions
    • Inflammation
    • Glaucoma
    • Cancer
    • Musculoskeletal disorders



What makes up the ECS?

The ECS has three main components – endocannabinoids (neurotransmitters), receptors, and enzymes.

To put it simply, endocannabinoids are little messengers that interact with their corresponding receptors, and produce a given outcome. Neurotransmitter messaging is how our bodies signal and initiate things to happen. 

Think of it like a lock and key. The endocannabinoids act as the keys, and they interact with the receptors (or locks), to produce an outcome. When the endocannabinoids are no longer needed, the enzymes come in to clean up and break them down.



Endocannabinoids are fatty acid derivatives that act as neurotransmitters. When needed, they are biosynthesized on demand in the post-synaptic terminal. Once created, they cross the membrane and travel backwards in a retrograde fashion to the presynaptic terminal where they activate the receptors, leading to inhibition of neurotransmitter release.

The two main endocannabinoids that have been studied so far are:

    • anandamide (AEA)
    • 2-arachidonoylglycerol (2-AG)

THC is similar to anandamide, though anandamide does not produce psychoactive “high” effects like THC. Anandamide does possess calming qualities, and is known as the “bliss molecule” – getting its name from the Sanskrit word for bliss “Ananda”.


Endocannabinoid Receptors

The two main endocannabinoid receptors are CB1R + CB2R:

    • CB1R – is mainly expressed in the brain and central nervous system.
    • CB2R – is mainly expressed in the peripheral nervous system and immune cells.

Cannabinoids also interact with various other receptors and ion channels such as the TRPV1 channel (transient receptor potential cation channel subfamily V member 1), which when activated by AEA is best noted for its role in synaptic transmission and pain regulation.

Cannabinoids can either act directly on a receptor to activate it (agonistic), or they can act indirectly by inhibiting other agonistic neurotransmitters from accessing the locks (an antagonistic effect) – the latter being kind of like “boxing out” the agonists in a microscopic basketball game.



Enzymes control the degradation of endocannabinoids once their use is fulfilled. The two main enzymes studied are:

    • fatty acid amide hydroxylase (FAAH) – breaks down AEA
    • monoacylglycerol lipase (MAGL) – breaks down 2-AG

Anandamide (like all endocannabinoids) are synthesized on demand when needed and then quickly broken down by their corresponding enzymes. Interestingly, the main reason AEA does not produce psychoactive effects is due to the speedy breakdown by enzyme FAAH.



Phytocannabinoids and the Endocannabinoid System – CBD & THC

While our bodies create their own endocannabinoids, the ECS is also designed to interact with external plant cannabinoids called phyto-cannabinoids.

The most prominent and studied phytocannabinoids found in cannabis and hemp are THC and CBD, but over 100 other plant cannabinoids have been discovered to date – including the lesser known: cannabigerol (CBG), cannabinol (CBN), and cannabicyclol (CBC).

THC is known to have many therapeutic benefits, but also comes with an intoxicating effect that causes one to feel “high.” THC binds to CB1R as an agonist (activator). Contrastingly, CBD acts differently on these receptors, and does not produce intoxicating effects. CBD acts as an indirect antagonist (blocker) to the CB1R receptor – which may suggest why CBD has been seen to have a tempering effect on the psychoactive effects of THC in certain studies.

Though research is still ongoing, CBD had been shown to have many potential benefits, include analgesic, anti-inflammatory, anticonvulsant and anxiolytic characteristics. The exact ways in which CBD acts on the Endocannabinoid System is still unknown, but there are a few key ways that research highlights.

While CBD has a low affinity (binding ability) with the CB1 receptor, it has an indirect effect by way of inhibiting the enzyme-breakdown of neurotransmitter Anandamide. This inhibition allows for AEA to say in the system longer and provide benefit [03].

CBD is also known to be a modest agonist (activator) of human 5HT1a serotonin receptor – suggesting CBD as having an “interesting and useful potential beyond the realm of the cannabinoid receptors” [06].

CBD is also known to stimulate the vanilloid pain receptors (TRPV-1 receptor) whose role is to mediate pain perception, inflammation, and temperature [08].



In Summary:

The ECS is a complex messaging system in the body that governs a wide array of physiological functions, such as: pain, inflammation, appetite, muscle control, energy balance, metabolism, sleep, stress, and mood. The body generates its own endocannabinoids on demand when needed, but compounds found in hemp and cannabis (phytocannabinoids) are uniquely suited to interact with our body’s ECS, with great potential to offer therapeutic benefit.

 It is exciting to think about the many potential ways that cannabis/hemp can play a supplemental role in the maintenance of our inner balance, but there is still much to be discovered.



Interested in learning more about CBD? Check out these other articles:




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