What Is the Endocannabinoid System and How It Works

6.9.2025 0 comments

Author: Trisha Houghton, CNS, ASIST

The endocannabinoid system is one of the most important yet least well-known of our body’s internal systems.

Though recently discovered, it turns out that it plays a role in so many different functions—from sleep to memory, appetite to pain control, and mood to immune function.

In this post, we’ll take a deep dive into the endocannabinoid system and learn what it does, what key components comprise it, and how it works.

We’ll examine a few of the issues that can disrupt endocannabinoid balance (including cannabis) and explore some of the myths and misconceptions about this system. Most important of all, we’ll address simple yet highly effective ways you can keep your endocannabinoid system functioning optimally for better overall wellbeing.

Introduction to the Endocannabinoid System: Why It Matters

The endocannabinoid system (ECS) is a “neuromodulatory system” that plays a role primarily in the function of your central nervous system and synaptic plasticity. But as you’ll see below, its usefulness extends to a lot more internal systems and functions, contributing to your health and homeostasis in many ways.

Key Components: Receptors, Endocannabinoids, and Enzymes

The endocannabinoid system is made up of three components:

• Cannabinoid receptors – CB1 receptors are present in the brain. They’re responsible for neurotransmitter regulation and adjust the body’s internal mechanisms based on feedback signals like hunger and satiety, relaxation and alertness, and feelings of being cold or hot. CB2 receptors are primarily present in immune tissues. They’re responsible for regulating immune response and inflammation control in our digestive tracts (combatting the pain and inflammation of inflammatory bowel conditions, for example).
• Endocannabinoids – Endocannabinoids (endogenous cannabinoids) are molecules produced by the body to stimulate the CB1 and CB2 receptors. They’re similar in structure to the cannabinoids found in the cannabis plant. The primary endocannabinoids are anandamide (AEA), and 2-arachidonoylglyerol (2-AG). They’re responsible for keeping your body’s internal systems operating efficiently and maintaining homeostasis.
• Enzymes – Enzymes are your body’s way of controlling endocannabinoids and their effect on the body. The enzymes 1, 2-diacylglycerol lipase and phospholipase A stimulate the production of endocannabinoids to trigger some internal effect. Тhen the enzymes hydrolase and monoacylglycerol acid lipase break down the endocannabinoids once they have stimulated the correct response in the body.

How the Endocannabinoid System Maintains Homeostasis

Because the discovery of the endocannabinoid system is so recent (1990s), there’s a lot science still doesn’t understand about what it does. It’s a highly complex and complicated system that is continually being studied to further understand it.

However, there are some basics about this bodily system that is known, and which you need to understand.

The Role of CB1 and CB2 Receptors in the Body

CB1 receptors are the most common cannabinoid receptors in the body. They are chiefly present in your brain and spinal cord. CB2 receptors are less common, and exist primarily in immune tissue and the peripheral nervous system (PNS).

The body produces endocannabinoids in many places around the body: in the brain, in the muscles, in immune cells, even in adipose tissue. They are created “on demand” when and as the body needs them. When produced, they are detected by the cannabinoid receptors and trigger a reaction.

For example, the production of endocannabinoids detected by CB1 receptors may reduce the pain of an injury, while endocannabinoids produced to be detected by CB2 receptors may signal to your body the presence of inflammation identifying an infection site.

The endocannabinoid system modulates multiple internal systems in a balanced way, turning signals on and off in context. It produces the necessary endocannabinoids to trigger the CB1 or CB2 receptors to affect change, then breaking down the endocannabinoids to prevent the possibility of “overcorrecting”.

How the ECS Affects Mood, Pain, Sleep, and Appetite

The complex interplay of cellular signaling that comprises the endocannabinoid system extends to a wide range of bodily functions, including mood regulation, detection of pain, and your sleep habits. It also controls your satiety and hunger regulation.

How exactly it does so is not yet understood. What is understood is that blocking CB1 receptors (which one weight loss medication in the past did) can reduce hunger, but it can also have a negative impact on mood.

The Connection Between the ECS and the Immune System

The endocannabinoid system is directly linked to the immune system.

The majority of CB2 receptors are present in immune cells, including B cells, T cells, and macrophages. These receptors, when activated by specific enzymes, can trigger a reaction in the immune cells—for example, cellular proliferation or the release of inflammatory cytokines.

The endocannabinoid system is directly linked to immune function—particularly the adaptive immune system. It helps regulate the immune system to respond to and eliminate threats, but prevents it from overcorrecting and ensures homeostasis is maintained.

It regulates immune cells, modulates inflammation, and even regulates stem cells, causing them to form into the new, healthy cells. The body needs these cells to repair or restore internal functions following infection or disease.

What Disrupts Endocannabinoid Balance?

There are a number of things that can impair and impact the delicate balance of the endocannabinoid system, including:

• Sleep loss – Poor sleep habits or chronic sleep deprivation can dysregulate the body’s production of endocannabinoids and then enzymes that control them.
• Stress – Chronic stress, as well as severe or extreme stress (such as in an emergency or traumatic situation), can also interrupt healthy ECS function.
• Diet – A diet that is high in fat and low in critical nutrients (like Omega-3 fatty acids or fiber) can negatively affect your body’s energy-regulating mechanisms, leading to a sluggish endocannabinoid system.
• Lack of exercise – Physical inactivity can lead to metabolic problems, which have been known to contribute to dysfunction of the endocannabinoid system.
• Substance abuse – Recreational drug and cannabis use and heavy alcohol abuse can interfere with the endocannabinoid system and increase the risk of other conditions (such as fatty liver disease or insulin resistance) that also impact the ECS negatively.
• Environmental factors – Endocrine-disrupting chemicals like parabens and BPA will affect the function of your endocrine system, which can also trigger dysfunction in the endocannabinoid system.
• Medications – Antibiotics, chemotherapy agents, and other medications may impact nerve function or cause nerve toxicity, which, over time, can impact your endocannabinoid system.

Alterations to your gut microbiota (resulting from poor diet, disease, medication use, etc.) can also cause metabolic health issues and affect your endocannabinoidome [1].

How Cannabis Interacts with the Endocannabinoid System

Tetrahydrocannabinol (THC), the psychoactive compound in cannabis, binds to the CB1 receptors in your body “with a high affinity”[2]. It acts like endocannabinoids, affecting your nervous system, mood, sleep habits, brain function, even learning and memory.

But because it’s from an unregulated external source, there is serious concern that it can lead to dysfunction or impairment of the endocannabinoid system.

However, there are some scientists who believe it’s worth exploring the possibility of cannabis-based treatments for a wide range of health problems. These health problems range from infectious disease to cancer, autoimmune disease, and even organ transplantation (using cannabis to suppress inflammation and prevent organ rejection).

The Future of ECS Research in Medicine and Mental Health

One study [3] wrote that, “since the endocannabinoid system is widely expressed in the body and deeply involved in the function of the neurological system, body metabolism, and bone homeostasis… medications that include cannabinoids such as THC and CBD may be used to treat nausea, chronic pain, sleeping disorders, or epilepsy. However, in some oncologic patients, administration of such medications may hold the risk of suppressing desired immunological reactions against pathogens and tumor cells…and immune-modulatory effects of cannabinoid-based medicines may be detrimental in other instances.”

There is a great deal more cannabinoid research required to understand how, exactly, cannabis impacts the ECS, both positively and negatively. But with every year, more is being discovered and greater understanding acquired.

There is real promise that cannabis-based treatments may offer very real therapeutic applications to helping treat a wide range of diseases and conditions once the endocannabinoid system is more thoroughly understood.

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Natural Ways to Support a Healthy Endocannabinoid System

The endocannabinoid system is complex and requires a careful balance to maintain its healthy function.

There are a lot of things you can do in your daily life to keep this crucial and highly delicate system operating smoothly:

• Eat right. There are certain foods that will provide your ECS with the nutrients it requires to function properly. Foods like hemp seeds, flax seeds, and olive oil are rich in the Omega-3s and essential fatty acids required to produce endocannabinoids. Flavonoids from dark, leafy greens and brightly colored fruits and veggies will also slow the breakdown of endocannabinoids, extending their viability in the body.Beta-caryophyllene (found in black pepper, sage, hops, cinnamon, and rosemary) can also reduce inflammatory response and improve function of the CB2 receptors that regulate immunity.
• Exercise. Research [4] has proven that physical exercise can trigger the release of endocannabinoids, which leads to mild reduction in pain, improved mood, even decreased anxiety. One study concluded that “During PE, the activation of vagal afferents…by the ECS produces stimulation of the PNS, which can activate the cholinergic anti-inflammatory pathway, and this can be considered a therapeutic strategy for reducing chronic inflammation and preventing many chronic diseases.”
• Avoid alcohol. Alcohol triggers inflammation in the body and stresses out your internal systems, including your ECS. Cutting back on alcohol also reduces the risk of metabolic diseases that can impair endocannabinoid system function.
• Get bodywork. “Bodywork” refers to therapeutic treatments that involve working with the human body with the aim of assessing and improving posture, proprioception, and enhancing the body-mind connection. Bodywork therapies include chiropractic adjustment, acupuncture, and massage. These therapies may support relaxation and indirectly benefit ECS balance through stress reduction.
• Take probiotics. Probiotics (particularly Lactobacillus acidophilus [5]) can improve gut health and reduce intestinal inflammation and discomfort. Early research suggests that they can also trigger the release of endocannabinoids and improve the function of cannabinoid receptors. The fact that they can minimize pain is one of the reasons they’re so often used to treat irritable bowel syndrome (IBS) and abdominal pain.
• Sleep more. A full night’s sleep (7 to 9 hours) is crucial for a healthy endocannabinoid system. Sleep loss, which often goes hand in hand with chronic stress, can impair your ECS and prevent it from efficiently maintaining homeostasis. By prioritizing your sleep and taking steps to improve sleep quality (creating a quiet, dark environment, following a sleep schedule, etc.), you can restore optimal function of this crucial internal system.

Common Myths and Misconceptions About the ECS

In the paragraphs below, you can see some of the most widespread myths about the endocannabinoid system, followed by information on what science actually says about them.

Myth #1: The endocannabinoid system only affects cognitive health

Truth: While the majority of your CB1 receptors are located in your brain and spinal cord, CB2 receptors are present in your immune cells and your peripheral nervous system. The endocannabinoid system regulates sleep, mood, appetite, pain, metabolism, cognitive function, memory, immune reactions, and a host of other functions throughout your entire body, not just your brain.

Myth #2: You only feel “high” in response to the THC in cannabis

Truth: A great number of things can stimulate the “high” feeling we equate with cannabis effects, from physical exercise (“runner’s high”) to sexual activity (orgasm releases endocannabinoids). Even massage can trigger the release of endocannabinoids.

Myth #3: All cannabinoids are the same

Truth: Endocannabinoids are produced by your body. Phytocannabinoids are produced by plants. Synthetic cannabinoids are manufactured. They all have similar effects on your body, due to their being detected by CB1 and CB2 receptors, but differ in origin.

Myth #4: Your ECS only plays a role in immunity, pain management, and memory

Truth: While these are the primary functions of the endocannabinoid system, the truth is that this system is integral to a wide range of roles in your body—including appetite, sleep, mood, and more. The ECS creates a “bridge” linking your brain, your immune system, your gut, and all of your organs.

Wrapping Up

The endocannabinoid system is crucial for healthy internal function and the maintenance of homeostasis in your body.

By giving it what it needs—diet, exercise, sleep, and reduction in alcohol intake—with emerging evidence suggesting possible benefits from probiotics and bodywork, you can keep this vital system running smoothly and efficiently.

A healthy ECS will contribute to keeping the rest of you healthy, too!

Since restful sleep is one of the most effective and natural ways to support your endocannabinoid system, prioritizing quality sleep can make a meaningful difference for your overall well-being.

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Frequently Asked Questions

How does the endocannabinoid system influence pain perception?

Endocannabinoids bind with the CB1 receptors and “negatively regulate neurotransmission throughout the nervous system” [6], effectively reducing your nervous systems’ sensitivity to pain. At the same time, the endocannabinoids binding with the CB2 receptors regulate inflammation in the body to reduce the swelling at disease or injury sites.

What effects does the endocannabinoid system have on mood?

Research [7] has shown that the endocannabinoid system can reduce anxiety, combat depression, and elevate mood. Certain activities—such as massage or physical exercise—can trigger the “high” feeling and boost your mood, even leading to feelings of euphoria.

How does the ECS regulate sleep patterns and cycles?

Science indicates[8] ECS activity fluctuates with sleep-wake cycles, with endocannabinoid levels naturally changing throughout the night to support sleep architecture.One study [9] found that “concentrations of anandamide are threefold higher at wakening than immediately before sleep”, suggesting a direct link between endocannabinoids and your sleep patterns.

Resources

The endocannabinoid system: Essential and mysterious

An introduction to the endogenous cannabinoid system

Review of the Endocannabinoid System

What to know about endocannabinoids and the endocannabinoid system

Beyond Cannabis: Plants and the Endocannabinoid System

The endocannabinoid system and brain function

ECS Explained: Immune and Endocannabinoid Systems

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