What You Need To Know About The Endocannabinoid System

Endocannabinoid system and receptors
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By now you may have already heard of the Endocannabinoid System. And, if you haven’t – we can help! **[link to article 1] You probably know just how vital this system is to keeping us in good health, and you likely understand the basics that make the ECS tick. Now, it’s time to dive a little deeper.

What you may not know is that the Endocannabinoid System is comprised of three interrelated parts:

Together, these three elements fulfill the biochemical demands of each other and help the entire system run smoothly. For now, we’ll focus on the ECS’s ‘inbox’ – its Endocannabinoid Receptors..

In cellular biology, a receptor is defined as “any of various specific protein molecules in surface membranes of cells and organelles to which complementary molecules… may become bound.”

Translate this definition to ECS receptors, and you’d get something like: “any of two types of G-protein coupled receptors on the surface membranes of cells to which endo and phytocannabinoids may become bound.”

While the words used here may seem complex, the concepts themselves aren’t as complicated as you might think. eCB receptors exist to collect inputs and relay their messages, and they do this by using the feedback that cannabis-like compounds provide.

If it’s helpful, think of eCB receptors as open containers that can be ‘filled’ with cannabinoids and unlocked by their effects. Almost like an inbox notification that is sent out only past a critical threshold – one major difference being that every message the ECS sends is important!

picture showing Possible glycosylation sites in the Endocannabinoid System


Like we said, there are two kinds of ECS receptors, both of which are woven into cell membranes and share a peculiar shape, so that one part of the receptor digs into the cell and the other part sits on top. These two types are called CB1-1 and CB-2.


CB1, short for cannabinoid-1, is the primary cannabinoid receptor found in the brain. It’s also the receptor that was discovered first (around 1991), thus the name. CB1 interacts with cannabinoids of all kinds, especially cannabinoids of the psychoactive variety: THC and Anandamide.

That’s probably why it was discovered first, after all. Easier to elicit the obvious effects of THC than the more subtle ones of CBD.

picture of CB1 receptro bonding sites image
Once activated, the brain’s CB1 receptor bonding sites ‘light up’. Courtesy of the Journal of Pharmacology and Experimental Therapeutics.

But CB1 receptors do much more than just getting a person high. They also heavily influence things like wellbeing, hunger, and pleasure. People that had CB1 temporarily ‘blocked’ for research purposes quickly became depressed, a concept that likely carries over into real life. It’s even theorized that the activity at a person’s CB1 receptors influences how optimistic and forward-thinking they are!

Another interesting feature: while there are huge amounts of CB1 receptors throughout most parts of the brain, these receptors are noticeably absent from the brain stem. That means cannabinoids, whether CBD or THC, are virtually impossible to overdose one.


While CB1 populates the brain, CB2 is present in greater concentrations in the body. These receptors can even be found on cells in every vital organ! From the muscles of the heart to the matrix of mitochondria and many places in between, CB2 receptors increase general health without producing psychoactive effects.

If you’ve ever used a hemp topical and experienced pain relief, you’ve witnessed firsthand how important these receptors really are. That topical only worked because the CBD molecules in it crossed through a few dermal layers and attached themselves to CB2 receptor sites in the connective tissue and fascia. Once the CBD bonded to its receptor, it was able to send an important message to other neurotransmitters, reducing inflammation in the process.


The idea that our bodies contain built in CB1 and CB2 receptors that respond specifically to CBD from the hemp plant is amazing enough. But the ECS’s versatility doesn’t stop there!

Remember from the definition at the start of this article that eCB receptors are G-protein coupled receptors, or GPCR’s. While what that means exactly is beyond the scope of this article, it’s highly relevant that GPCR’s are the largest and most prevalent group of receptors found in the human brain. And what this means is that endocannabinoid receptors are able to interact, and even occasionally join forces with, other neurotransmitters.

For example, serotonin and THC share the same heterodimeric receptor in certain instances. This may be why THC does not cause hallucinations like other molecules (eg, DMT) that ‘hit’ the serotonin receptor do. Cannabinoid receptors’ ability to interact with many different GPCR’s is at the heart of why phytocannabinoids exert gentle holistic effects, not harsh isolated ones.

CBD is known to have a high affinity for one GPCR in particular, the TRPV1 receptor. That’s short for the lengthy term transient receptor potential cation channel subfamily V member 1.

TRPV1 interacts with vanilloid, capsaicin, and other natural compounds, and is the system responsible for regulation of body temperature and perception of pain. You can thank TRPV1 for the taste of a hot pepper and for the needed pain signals of an unexpectedly hot frying pain. The primary reason CBD is so effective for pain relief is because it helps bring balance back to this interesting sensory system.

As usual, the Endocannabinoid System provides a powerful example of the body’s innate ability to heal itself. Its CB1 and CB2 receptors are dynamic enough to communicate with any type of cannabinoid; widespread enough to relay health benefits to virtually any physiological location. Without these receptors the body would lose its ability to self-regulate. But, with them, there is synchronization towards healing and health.

At Legends Health our goal is to help educate as many people as possible about all the benefits of CBD. The founder of our company had several autoimmune disorders that effected her life, and finding CBD enabled her to stay away from BIG Pharma prescriptions. We think it’ll do the same for you!

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