Understanding the Endocannabinoid System, How It Works, and What It Does

In middle school and high school science classes we all probably learned about some of the “systems” within our bodies. The most frequently remembered is what we call “the nervous system” (which contains two separate systems, but we’ll come back to that later!). One system I doubt any of us learned about in school is the endocannabinoid system.

That’s okay because that’s what we’re here for today! To learn the basics – what the endocannabinoid system is, what its primary functions are, and how it works. Of course, keep in mind that research into the ECS is ongoing, and this is only what we know so far.

What is the Endocannabinoid System?

Simply put, the endocannabinoid system is a complex system of receptors, endocannabinoids, and enzymes that work together to help regulate normal everyday functions, including sleep, mood, and more.

It was the isolation of THC and CBD, cannabinoids primarily responsible for the known effects of cannabis plants, that gave way to discovering the ECS in the first place.

Within a few decades, we were able to isolate not only the receptors that these cannabinoids bind to but also identify at least two endocannabinoids that help maintain various functions throughout the body.

What Are Endocannabinoids?

Okay, back things up – receptors and enzymes we’ve probably all heard of at some point or another… but endocannabinoids? If the term is unfamiliar, don’t feel bad, endocannabinoids weren’t discovered until the early 1990s.

Endo is short for endogenous, which means “within,” making it a fitting and simple name for cannabinoids that are naturally produced within our bodies.

These endocannabinoids are just like the cannabinoids produced by cannabis plants (which are also known as phytocannabinoids), except they occur within humans rather than plants.

The two endocannabinoids that researchers have been able to isolate are anandamide (AEA) and 2-arachidonoylgylcerol (2-AG). Researchers believe there are more endocannabinoids but have yet to positively identify and/or isolate any since the discovery of 2-AG.

When cannabinoids bind to receptors within the ECS, the process is the same whether the cannabinoids are naturally occurring endocannabinoids, introduced external phytocannabinoids, or synthetic cannabinoids.

How Does the Endocannabinoid System Work?

The ECS is unique in many ways compared to other systems in the body, and we’re still trying to understand the complexities of its role in our overall health. However, in the decades since its discovery, researchers have at least been able to pin down its core components and how they work together.

Cannabinoids Bind to Cannabinoid Receptors

Cannabinoids seek out and bind to cannabinoid receptors that can be found throughout the body. Once a cannabinoid binds to the receptor, it releases a neurotransmitter that, based on the cannabinoid, sends signals that trigger one or more various responses throughout the body.

As we just discussed, our bodies produce cannabinoids naturally – but external cannabinoids like those from cannabis bind to and activate those same receptors, creating a wide range of effects.

Neurotransmitters and Retrograde Signaling

In most systems within our body, neurotransmitters are released by a presynaptic cell, which sends a message across the synapsis to attach to specific receptors or postsynaptic cells.

The ECS, on the other hand, works in reverse – creating endocannabinoids on demand to maintain different functions as needed. Basically, endocannabinoids are created by the postsynaptic cell (often in response to an imbalance somewhere), travel backward across the synapsis to the presynaptic cell, where it then binds and activates a receptor.

When the body does this naturally, it produces endocannabinoids in response to a need. Once the body determines that things are regulated, enzymes will break down the cannabinoids, thus preventing overcorrecting the problem (or ending your buzz if you’ve introduced THC or other intoxicating cannabinoids).

What Are Cannabinoid Receptors, and Where Are They Found?

Cannabinoid receptors were first discovered in the early 1990s, so everything we’ve discovered has only been within the past 30 years or so. What we can say for sure is that at least two cannabinoid receptors, also known as CB receptors, are found in various parts of our bodies.

It’s possible there may be a third cannabis receptor, but that has yet to be confirmed (or denied) by researchers.

Meet the CB1 and CB2 Receptors

Officially dubbed CB1 and CB2, these receptors are the ones responsible for maintaining several regular daily functions, as well as controlling the way our minds and bodies respond when external cannabinoids are introduced.

CB1 Receptors and the Central Nervous System

CB1 receptors are mostly found in the brain and central nervous system, though some have been found in peripheral organs and tissues. They impact functions such as memory, movement, and emotion.

CB2 Receptors and the Peripheral Nervous System

CB2 receptors are primarily found in the peripheral nervous system, with high concentrations in immune cells, the gastrointestinal system, and the spleen. These receptors play an important role in moderating inflammation and immune responses.

What Does the Endocannabinoid System Do?

The endocannabinoid system is responsible for maintaining balance within numerous functions and systems throughout the body, and it’s widely accepted that its main role is to maintain homeostasis.

Basically, it’s there to keep everything in check and produce endocannabinoids on demand to keep that balance. This is why some researchers believe that endocannabinoid deficiencies could be one reason behind several degenerative and/or neurological conditions and disorders that may benefit from medical marijuana treatments.

Physiological Connections to the ECS

CB1 receptors can reduce pain perception, stimulate appetite, regulate energy, and metabolism, while CB2 receptors reduce inflammation and improve overall immune responses.

• Pain/inflammation
• Immune responses
• Appetite/digestion
• metabolism
• Sleep

Psychological Connections to the ECS

CB1 receptor activation can produce effects that reduce anxiety and promote relaxation, improving our ability to learn and form memories. However, excessive CB1 activation by THC may impair short-term memory.

• Mood
• Anxiety
• Depression
• Learning and memory

THC, CBD, and the Endocannabinoid System

THC and CBD both interact with the ECS in completely different ways. While THC binds easily with CB1 receptors in the brain (causing the associated “high”), it does bind to CB2 receptors as well.

CBD, on the other hand, has a low affinity for both CB1 and CB2 receptors. It works more “behind the scenes” in a way that influences our bodies to produce more endocannabinoids naturally.

Research on the Endocannabinoid System Still Has a Long Way to Go

Hopefully, as we continue to learn more about the ECS, we can discover things like how endocannabinoid deficiency may play a part in conditions like migraine, fibromyalgia, or IBS or find lasting treatment for conditions that have long plagued us as devastating and incurable like Alzheimer’s, Parkinson’s, cancer, and so many others.

It’s been over eight years since I last wrote about the endocannabinoid system, and in that time, very little about our understanding of this complex system has changed. However, that doesn’t mean that research isn’t ongoing, that there isn’t a lot that has been learned already, or that there’s still not a ton more to discover.