Health & Wellness

An Introduction to the Endocannabinoid System

By Elizabeth Millard

Take a look at old anatomy charts, and you’ll likely find all the well-known interior structures like the circulatory system’s river-like stretches and the lymphatic system’s pockets of lymph nodes. What you won’t see listed is the endocannabinoid system (ECS), even though it affects a significant amount of your body’s functions, according to Jordan Tishler, MD, a Harvard physician and president of the Association of Cannabis Specialists.

“This is a very old system in mammals, including us, that’s only been recently recognized within the past few decades,” he says. “Because of that, we’re still learning about the breadth of the system’s impact. But what we do know is very exciting.”

Here’s a look at how ECS operates in the body, and why it matters for a range of conditions, from anxiety to chronic pain to neurological diseases.

Endocannabinoid 101

Unlike the circulatory system, respiratory system or musculoskeletal system that have very specific functions like delivering blood, using oxygen, or moving us around, ECS is not function-focused in that way, Dr. Tishler says.

Instead, its purpose is to regulate the way that all the other systems work in the body, in order to maintain homeostasis—the state of equilibrium and optimal functioning.

If you think of your body as a technologically advanced machine, like a car, then there are systems specific to the vehicle’s operation. For example, one system delivers fuel to the engine, another is connected to rotary motion necessary for making the car move, yet another creates power through controlled combustion, and so on.

In this analogy, the ECS system is the computer that allows all the systems to work together seamlessly to get you where you need to go. It also fine-tunes those systems on a regular basis so they’re working as optimally as possible.

It does this through a series of neurotransmitters—called endocannabinoids—as well as receptors that are located throughout the entire body. As the transmitters bind to the receptors, an array of cognitive and physiological processes is regulated.

Not only are these transmitters and receptors important for the brain, where they regulate processes like memory, but they’re also at work throughout the body, Dr. Tishler notes.

“The ECS has as much going on in the gut as it does in the brain,” he says. “It’s in every system, from your lungs, kidneys, and bone marrow to your immune response, reproductive health, and pain modulation. ECS affects pretty much everything in the body you can name.”


The Endocannabinoid System (ECS) is connected to every part of your body, including your brain, lungs, kidneys, and bone marrow.

Role of Receptors

Two primary types of receptors are involved, and it’s important to classify them to understand how tetrahydrocannabinol (THC) and cannabidiol (CBD) are used by the system:

  • CB1 receptors are primarily found throughout the central nervous system and brain, but are also present in some organs and tissues. These are the receptors most closely involved with anxiety regulation, pain control, concentration, and memory. Some research has also linked these receptors to metabolic function and obesity.
  • CB2 receptors are mostly in white blood cells and areas related to immune function, such as the spleen and tonsils. The receptor was discovered a few years after CB1, as researchers sought to understand how cannabinoids affected the immune system.

Both of these receptors can be activated by the endocannabinoids you make naturally, and also by plant-based cannabinoids, such as THC and CBD—the two most prominent components found in cannabis. But, how each interacts with the receptors is different, says Michelle Weiner, DO, MPH, of the Spine and Wellness Centers of America.

THC binds to the receptors directly, she notes, but CBD is a modulator. When CBD is introduced, especially when it’s acting solo (as with CBD oil), it blocks the enzyme that breaks down your receptors, Dr. Weiner says.

“That’s why CBD oil can be a wellness supplement, because it has a protective effect,” she says. “It protects your ECS receptors so that your own endocannabinoids can bind to them, and it can also stimulate production of those neurotransmitters. It helps maintain balance in the body.”

THC and CBD together seems to be particularly effective for numerous conditions and issues, adds Dr. Tishler. That’s because they work in concert to activate the receptors and cause a cascade of biological effects. He calls them the “lock and key” of receptor function, with both having a more limited effect when used alone.

CB1 and CB2 receptors interact with TCH and CBD. These receptors are located throughout the human body.

ECS vs. Opioid Receptors

“When you think about how receptors are in so many different areas of the body, it makes sense that cannabinoids would be helpful for treating such a wide range of conditions, says Karen Munkacy, MD, who founded the first physician-owned medical marijuana dispensary in Massachusetts.

One place where ECS receptors are lacking? The brain stem, she says, and that’s a good thing. That’s the part of the body that controls breathing and consciousness, so few ECS receptors there means that if you were to “overdose” on cannabinoids, your breathing wouldn’t get affected.

By contrast, the brain stem has a large number of opioid receptors—which is why an opioid overdose causes loss of consciousness and depression of the respiratory system. With opioids, the body “forgets” how to breathe.

“The ECS is very different, “Dr. Munkacy says. “There’s no lethal dose of medical marijuana, for instance. Although cannabinoids can affect serotonin and dopamine to address anxiety and depression, you won’t see the kind of risks that you would if you were using opioids to treat those conditions.”

Work to Be Done

Although the ECS is much better understood than just a few decades ago, research still needs to be done in terms of how to utilize plant-based cannabinoids for the best effect, believes Dr. Tishler. For example, he notes, there’s been extensive research on THC, but more studies need to look at how the system uses CBD in humans—as opposed to mice, which have been the subject of most studies.

Also, Dr. Munkacy adds, the “stigma” of cannabis use makes it difficult to get research funded and approved in the United States.

“There are so many conditions where medical marijuana can be helpful,” she says. “But research is limited, and also, we need more physician education in general.”

Another challenge is at the individual patient level. One of the difficulties with understanding potential imbalances in your ECS is that endocannabinoids break down quickly, says Dr. Weiner, and they don’t show up on tests in the same way that other, better-known substances might.

“If you’re deficient in something like vitamin D, that will show up on a blood test and you can take a supplement to correct that,” she says. “But when you’re deficient in endocannabinoids, there isn’t currently a way to test for that. The science needs to catch up in that area.”

Still, even with those caveats, there’s been considerable progress made since the receptors were first cloned in the early 1990s. And that progress is driving interest in products like CBD oil and medical marijuana for such a breadth of conditions.

“Basically, especially as we age, many of us develop imbalances in the systems in our body,” says Dr. Weiner. “Focusing on ECS helps us get to the root of these imbalances, rather than just treating the symptoms that appear in each system.”

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