Most people have heard an earful about the health benefits of CBD — its effects on stress-response, inflammation & immunity, pain, mood, and more — but the question of how and why CBD works opens a window onto a vast & complex system that science is still making sense of: the Endocannabinoid System (ECS).
The outlines of the ECS emerged during the 1960s and 70s, from research into the effects of cannabis on the human body.
Scientists were able to isolate numerous phytochemicals from the cannabis plant — phytocannabinoids (“phyto” means “plant”) — and by studying their effects revealed a web of receptors, enzymes, and biochemical pathways involved in manufacturing & using the body’s own form of cannabinoids: endocannabinoids (“endo“ means "originating within the body").
Although research focused primarily on humans and other mammals, it turned out that we share these neurochemicals with most members of the animal kingdom, including mammals, birds, amphibians, fish, and even sea urchins. It’s now clear that the endocannabinoid system (ECS) evolved almost 600 million years ago.
Because the ECS arose so early, as animals evolved into more complex beings it became connected to many different physiological and neurological functions — which we’ll explore more in future articles. For now, here is a brief introduction to this vital system...
Stars of the Endocannabinoid System
- Endocannabinoids (eCBs)
- Cannabinoid receptors (CB receptors)
- Enzymes that synthesize and break down eCBs
Endocannabinoids (eCBs)
Neurotransmitters like serotonin and dopamine are chemical messengers of the nervous system. Similarly, endocannabinoids (eCBs) are the messengers of the ECS, and are produced throughout your body.
The two key eCBs circulating in your body are anandamide and 2-arachidonoylglycerol. Just like the phytocannabinoids in cannabis, these neurotransmitters are built from lipids (fats or oils). (The lipid-based structure of cannabinoids is the reason why THC and CBD are fat-soluble...and why your typical cannabis or hemp extract is delivered in an oil base like coconut or butter.)
Anandamide was discovered in the 1990s and gets its name from the Sanskrit word ananda, or “bliss.” This molecule operates throughout the endocannabinoid system and is involved with appetite, memory, and pregnancy, to name just a few of its functions. It’s even been identified as the source of the “runner’s high” experienced during or after intense exercise.
2-ArachidonoylGlycerol (2-AG) might not have a glamorous name, but recent scientific findings suggest that it is at least as important as its famous sister molecule, anandamide. 2-AG has been linked to our emotional states, protection from seizures, and maintaining cardiovascular health. That contented feeling you experience after orgasm? That’s 2-AG.
Cannabinoid receptors (CB receptors)
If eCBs are the messengers, then cannabinoid receptors are the guards posted at the city wall, waiting for the messengers. Receptors sit on cell surfaces, waiting for specific neurotransmitters to bind to them. Depending on the type of cell the receptor is on, the downstream effect will rapidly impact immunity, sensation, mood, and even consciousness.
We have CB receptors throughout our bodies, guarding a wide variety of cell types & responses. Different cell types have different receptors, which are sensitive to different types of eCBs. The two main receptors of the endocannabinoid system are CB1 and CB2.
CB1 receptors are essential for a healthy functioning brain and are one of the most common receptors in the entire nervous system. Depending on what region of the brain they are located in, they can be moderators of your memory, mood, motor function, or your perception of pain. These brain receptors are also responsible for the psychoactive properties of cannabis when THC binds to them.
Although CB1 receptors are most common in the central nervous system, we find them throughout the human body at lower densities. In other parts of the body, CB1 receptors also have roles in pregnancy, hormone production, cardiovascular health and digestion.
CB2 receptors are most often found on the cells of our immune system. They help moderate inflammation and our immune response to pathogens. If you use cannabis products to combat conditions of an overactive immune system (i.e. arthritis, asthma, allergies, autoimmune disorders or digestive issues like inflammatory bowel disease) you can thank your CB2 receptors.
Special Effects of CBD
Most cannabinoids can bind to both types of receptors — CB1 & CB2. This is true for both the endocannabinoids — anandamide & 2-AG — and for phytocannabinoids like THC.
However, the phytocannabinoid CBD doesn’t directly trigger either receptor. Instead, it modifies the receptors' ability to bind to cannabinoids.
Additionally, CBD plays a larger role in the endocannabinoid system: influencing other types of receptors, while also enhancing your natural levels of endocannabinoids by occupying certain enzymes.
Enzymes: Building & Recycling eCBs
So far we’ve discussed the messengers and the message-receivers, but who makes the messenger?
Your body has a whole suite of molecules devoted to controlling when & where eCBs are produced, and how quickly they get sequestered or broken down. You might think of these molecules as the administrative system, making sure the messenger is sent exactly when and only when desired.
Endocannabinoids are lipid-based neurotransmitters — which means they are synthesized from fats. Your body has a number of different enzymes that work together to transform fatty substances into anandamide and 2-AG. When your body gets the signal to produce eCBs, these enzymes are put to work.
One important thing we’ve learned about this process: increasing your dietary intake of omega-3s and other essential fatty acids may help your body boost its production of eCBs, because these fatty acids are specific building blocks for eCBs.
Sending the Messenger...
Cannabinoids are fat-soluble, but your body is mostly composed of water. In order for cannabinoids to travel through your body and reach their targets, they need to be escorted by endocannabinoid transport proteins. Much the way soap disperses oil into water, these proteins help eCBs flow smoothly through the body’s waterways.
...Killing the Messenger
Every “on” switch needs a corresponding “off” switch.
Once anandamide and 2-AG have delivered their messages, the body needs a way to prevent them from continuing to stimulate the ECS indefinitely. eCBs are rapidly moved by transport proteins to storage sites and/or delivered to enzymes that degrade eCBs.
The two most-studied enzymes in the ECS are FAAH (which degrades anandamide) and MAGL (which breaks down 2-AG).
FAAH is especially interesting: A genetic variation in 20% of adults impairs their FAAH enzyme — and the result is that these people have increased levels of anandamide and are generally less anxious. Because CBD inhibits these enzymes it tends to increase the body’s levels of feel-good anandamide and 2-AG.
A Growing Family
Each eCB can bind to multiple receptors and vice versa — a complex web of relationships. To add to this complexity, there are other molecules that can facilitate or interfere with this binding.
Like an intricate family tree, the ECS family keeps growing as scientists learn more about each individual’s numerous relationships.
Because it’s involved with so many aspects of human health, research on the endocannabinoid system has exploded since its discovery less than 30 years ago. In recent years, thousands of original research papers have been published on eCBs. It’s amazing that even with all that research, we’re only just starting to grasp the true potential of this system.
Supporting a Healthy ECS
One major takeaway from these studies is the unfortunate reality that the endocannabinoid system is very easy to throw out of balance. Stress levels, diet and exercise all influence your body’s ECS, and our modern lifestyles may be taking a toll on this natural system.
If you are trying to rebalance your endocannabinoid system, the recent legalization of cannabis and hemp products in many states and countries has made self-experimentation possible. There are more than 100 different phytocannabinoids — including THC, THCa, THCv, CBD, CBDa, CBN, CBG, etc — and each one can have slightly different interactions with the CB receptors throughout your body.
However, because CB receptors control so many different aspects of your nervous and immune systems, and because of genetic variation in enzymes, it isn’t possible to truly predict what reaction you’ll have without self-experimentation.
In the long run, scientists are developing ways to target specific cannabinoid receptors in localized areas of the body or brain without triggering the body’s entire endocannabinoid system. This will be especially effective for people suffering from very specific ECS disorders and who need more than a holistic approach.
An alternative solution to dosing with phytocannabinoids is to boost your body’s natural production of endocannabinoids. This way, your body can deliver eCBs to the parts of your body that need them the most.
In the next article in this series, we explore different options to help naturally restore balance to your body’s endocannabinoid system.
Written by: Genevieve R. Moore PhD
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