Cannabinoid Receptors and the Endocannabinoid System


Have you ever wondered why cannabidiol affects different people so differently?

It’s all thanks to the cannabinoid’s ability to activate something called the endocannabinoid system, or ECS, a “master regulatory system” that all of us have. Cannabidiol’s activation of this system gives it that almost-uncanny ability to help people with whatever they’re struggling with!

So if you’ve wanted to learn more about the ECS, this article will tackle the subject. 

Endocannabinoid Function 101

What the endocannabinoid system does is simple: it helps your entire body maintain balance, or homeostasis, by allowing every other major physiological system to communicate with the rest. It’s your body’s version of a thermostat. 

“We all have an endocannabinoid system,” affirmed molecular biologist and cannabinoid expert Robert Melamede at a Harvard University speech. “The miracle of this is that the endocannabinoid system regulates everything in your body — immune, digestive, cardiovascular, skin, bone, reproductive — from your conception until your death.”

Here are some more things your body relies on its endocannabinoid system to take care of:

  • Sleep
  • Mood
  • Hunger
  • Memory 
  • Energy balance
  • Emotional stability

When was the ECS discovered?

Cannabinoids like cannabidiol were discovered way back in the 1940s, but it wouldn’t be until much, much later that scientists realized how cannabidiol worked. 

Early glimpses of understanding came in the early ’90s when the endocannabinoid system, or ECS, was first discovered. It turned out that people were responding so well to phytocannabinoids like cannabidiol precisely because they were so similar in function to the endo-cannabinoids their bodies were already producing! Suddenly cannabidiol’s role made perfect sense. It was merely getting plugged into a pre-existing system. 

But let’s focus back on the ECS for a second. Research teams from the Hebrew University of Jerusalem kept searching and discovered a first endocannabinoid, anandamide, that was responsible for regulating mood and emotional behavior. Anandamide’s nickname? The “bliss molecule.” The discovery of a second cannabinoid, 2-AG, followed soon after. 

The ECS’s many parts

The ECS is made up of three major parts: endocannabinoids, endocannabinoid receptors, and endocannabinoid enzymes. Here are the details. 

  1. Endocannabinoids like anandamide and 2-AG are synthesized from the fats we eat and secrete virtually all the time, especially when the body needs a little extra help fighting stress. 

Because they’re produced on-demand, endocannabinoids (eCB’s) can easily maintain homeostasis. They’re even involved in the “runner’s high” you might get from exercise. Endocannabinoids can bind to both CB1 and CB2 receptors in the process ‘smoothing out’ neurotransmission and helping other neurotransmitters (like GABA or serotonin) function at their best.  

  1. Endocannabinoid receptors like CB1 and CB2 receptors are what pick up the messages endocannabinoids send. They’re found throughout every region of the body but especially in vital organs (like the heart) and the central nervous system (including the brain). In fact, CB1 is the most popular receptor of its type within the entire brain! 

Just not within the brain stem. This especially sensitive area contains virtually no endocannabinoid receptors, which is why cannabinoids like tetrahydrocannabinol and cannabidiol are almost impossible to overdose on. 

  1. Endocannabinoid enzymes do two essential things: produce endocannabinoids and break them down. These enzymes help endocannabinoid levels stay in the optimal range, at least in theory. Sometimes eCB levels still get out of wack, exactly where the importance of cannabinoids like cannabidiol comes in.

How to activate your ECS

With cannabinoids

The endocannabinoid system, like anything else in your body, can get stressed into depletion mode over time. Just think: what happens when you overeat sugar, spiking your insulin levels again and again? Insulin resistance, that’s what, which eventually leads to type II diabetes. 

In the ECS’s case, chronic stress — not sugar — is the culprit, but there’s still no need to worry. Nature has given us a practically perfect solution in the form of cannabidiol. This cannabinoid can activate endocannabinoid receptors in much the same way that anandamide or 2-AG can, conferring all sorts of potential health benefits. 

Even if all else fails, cannabidiol can also inhibit the very endocannabinoid enzymes, like FAAH, responsible for anandamide’s breakdown. Slower enzymatic breakdown = more available anandamide = more receptor activation = a healthier, happier, more balanced you! 

With terpenes

Cannabidiol’s activation of the ECS is impressive enough, but nature goes one step further. Many of the terpenes present in full-spectrum hemp oil can bind to endocannabinoid receptors, too. Some terpenes appear to change the shape of these receptors, opening them up so that more substantial amounts of cannabidiol can reach the right binding sights. 

And one of hemp’s most prevalent terpenes, beta-caryophyllene, hits CB2 receptors nearly as strongly as cannabidiol does! “[…] Daily intake of 10–200 mg of this [terpene] could be a dietary factor that potentially modulates inflammatory and other pathophysiological processes via the endocannabinoid system,” attests one landmark study

While both cannabinoids and terpenes activate the ECS, the best path forward seems to call for some combination. 

Indeed, full-spectrum hemp’s specialized blend of cannabinoids, terpenes, flavonoids, chalcones, and more provide the endocannabinoid system with everything it needs to maintain full-body balance. Studies are finally starting to back this concept up; one study found that full-spectrum cannabidiol was four times more effective than cannabidiol isolate. 

Through lifestyle

There’s one more way to activate your ECS that you should know about — and it doesn’t call for ingesting any cannabinoids or terpenes at all!  

Instead, it involves eating well and moving well. Endocannabinoids, after all, are produced by the essential fatty acids we eat, which is part of why these fats are necessary in the first place. By eating plenty of omega 3’s today, you can likely keep your ECS from getting ‘run down’ in the future. 

Movement is essential, too. Some studies have found that exercise, yoga, and even acupuncture have a mildly “cannabimimetic” effect — that is, they provide many of the same mental and physical benefits of cannabinoids. Maybe all those cannabidiol-yoga enthusiasts are onto something.