Beginner’s Guide to the Endocannabinoid System

Published November 20, 2023
Beginner’s Guide to the Endocannabinoid System - Secret Nature

Human brain chemistry is more complex than any mechanistic system could ever describe. The precepts of medical science that reigned in the 20th century have been forced to give way to the reality that the human mind could never conceive of something as complex as the brain in which it seems to be housed.

One way in which this has become clear is in the mystery of the endocannabinoid system. Why is it, exactly, that a system exists within human neurochemistry that seems almost custom-tailored to respond to cannabinoids, which are exogenous compounds? The brain has even gone so far as to seemingly invent its own cannabinoids in their absence, resulting in an internal, endogenous cannabinoid system ever-poised to respond to chemicals only found in a single species of plant.

Why is it that the structure of the human brain corresponds to the structure of cannabinoids? Could the universal mathematical language of fractals be at play, or some sort of coevolution? We’ll leave that to the theorists and stick to the basic facts in this assay: What the endocannabinoid system is, what it does, and how it interacts with cannabis-derived cannabinoids.

What are cannabinoids?

Cannabinoids are curious compounds so-named for their sole appearance in Cannabis sativa, a plant with nearly universal distribution throughout Eurasia. With unique structures and properties not found anywhere else in nature, cannabinoids have potent antioxidant properties while also interacting strongly with certain systems in the human brain.

While the term “cannabinoid” has referred traditionally only to cannabis-derived compounds, plant-derived or “phytocannabinoids” so closely resemble the structure of certain compounds found naturally in the human brain that the term “endocannabinoid” has come to be equally accepted in scientific literature. Even though endocannabinoids aren’t found in cannabis, they’re so similar to cannabis compounds that the name naturally follows.

What are phytocannabinoids?

Phytocannabinoids are the compounds first given the name “cannabinoid,” and they’re found solely in Cannabis sativa. Certain plant species, such as flax, contain cannabinoid-similar or “cannabimimetic” compounds, but true phytocannabinoids are found solely in cannabis. The prefix “phyto” designates that these compounds are found in plants.

Examples of phytocannabinoids

 - Tetrahydrocannabinol (THC)
 - Cannabidiol (CBD)
 - Cannabigerol (CBG)
 - Cannabinol (CBN)
 - Cannabichromene (CBC)

What is an endocannabinoid?

An endocannabinoid is a cannabinoid-like compound that is produced by the human brain, even without any exposure to cannabis. All human brains produce endocannabinoids, leading scientists to identify an endocannabinoid system that regulates these compounds and puts them to use throughout the body.

Examples of endocannabinoids

 - Anandamide
 - 2-AG
 - Virodhamine

What is the endocannabinoid system?

The endocannabinoid is a natural system in the human brain of unknown origin, the sole purpose of which appears to be the processing of cannabinoids found in plants and cannabinoid-like compounds found in the brain. Endocannabinoid systems are also found in most animals, giving rise to the question of whether these systems emerged in animal and human brains before or after they appeared in cannabis.

What does the endocannabinoid system do?

The endocannabinoid system serves various functions throughout the brain and body, mainly regulating pain, inflammation, mood, and metabolism. Certain receptors and signaling substances in the endocannabinoid interact with your endorphin system while others assist in reducing inflammation through managing oxidative stress. These functions occur even in the absence of plant-derived cannabinoids, but phytocannabinoids also significantly impact the functioning of the endocannabinoid system.

Do phytocannabinoids affect the endocannabinoid system?

Yes, the endocannabinoid system almost seems designed to receive and process cannabinoids found in plants with certain receptors dedicated specifically to cannabinoids. In other cases, cannabinoids affect systems that are also impacted by non-cannabinoid compounds. Let’s take a look at a few examples of interactions between endogenous cannabinoid systems and plant-derived cannabinoids:

CB1 and CB2 receptors

These two receptors in the human brain were named “cannabinoid receptor 1” (CB1) and “cannabinoid receptor 2” (CB2) simply because it appears they only interact with phytocannabinoids and cannabinoid-mimicking compounds in the human brain. These receptors are most strongly affected by THC, particularly CB1, which is primarily responsible for THC’s intoxicating effects.

CB2, on the other hand, primarily impacts inflammation by acting on the peripheral nervous system — CB2 activation does not cause intoxication even though it also occurs when THC is ingested. Non-THC cannabinoids can also affect CB2, allowing inflammation relief without intoxication.

Other mechanisms of action

Out of all the 100+ discovered cannabinoids, no two interact with the human body and nervous system in exactly the same way. CBD, for instance, does not impact your conventional cannabinoid receptors to any significant degree and instead mainly acts at the serotonin and vanilloid bonding sites located throughout your nervous system. CBG, for its part, has a massively wide range of potential action that includes, but is not limited to, immune benefits.

What is endocannabinoid deficiency?

The role of cannabinoids in human health is not always a positive one. It appears, for instance, that human beings can become deficient in cannabinoids, in which case using phytocannabinoids becomes a therapeutic instead of a supplementary exercise. Clinical endocannabinoid deficiency (CED), first highlighted by Dr. Ethan Russo, occurs when activation of endogenous cannabinoid receptor sites falls below baseline thresholds, impedimenting the flow of human neurochemistry. 

What are the symptoms of endocannabinoid deficiency?

Dr. Russo and other cannabis scientists believe endocannabinoid deficiency may contribute to the general sense of malaise now affecting many adults, characterized by anxiety, depression, digestion issues, and sleep disorders. Overall, the vitality of the human body appears to only reach peak levels when endogenous cannabinoids are flowing optimally, a process that phytocannabinoids, it seems, can sometimes improve.

Can endocannabinoid deficiency be treated with phytocannabinoids?

Some researchers, Dr. Russo included, believe that clinical administration of cannabinoids may be a viable approach to endocannabinoid deficiency. Clear methodologies have yet to be established, however, and there are considerable differences between ingestion methods.

It’s not the case that every single instance of cannabis use inevitably helps with endocannabinoid system imbalance. Using cannabinoids the wrong way, in fact, has the potential to perpetuate or even worsen endocannabinoid destabilization.

What’s important is using cannabinoids in a conscious way, starting with low doses and absorbing as much of the knowledge on the subject as you can. Then, you’ll be able to make educated choices regarding dosing and cannabinoid ratios that will ensure your experience is beneficially balancing.

Which phytocannabinoids are best for the endocannabinoid system?

Cannabinoids in the THC family have the most potential to disrupt the endocannabinoid system, but they also have immense potential to heal. If you’re not sure about THC (which includes delta 8 and THCA), you might want to start with CBD or CBG, both of which are non-intoxicating and have reduced inherent capacity for endocannabinoid system destabilization.

How to take phytocannabinoids

Whichever cannabinoid you choose to take, understand that:

 - Edible products provide long-lasting but weaker experienced effects,
 - And inhaled products offer intense but shorter-lasting effects.

Those seeking a small, long-release dose may prefer edible cannabinoid products. Individuals seeking instant endocannabinoid rebalancing, however, will gravitate toward inhaled cannabinoid products instead.

The endocannabinoid system: Tying it all together

The endocannabinoid is a vastly complex and ultimately mysterious component of the human neurochemical puzzle. Like the mythical chicken and the egg, which came first: cannabis, or endocannabinoids?

We may never know the answer to this overarching question, but simpler questions are being answered all the time. The endocannabinoid system is proving instrumental in areas of human health nobody predicted, raising the value and validity of cannabis-based treatments and products worldwide. Try cannabinoids in a new light, knowing that there’s already a system in your body seemingly designed to welcome them home.

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