What Is the Endocannabinoid System? How the ECS Works

The endocannabinoid system, often shortened to the ECS, is a cell-signaling network found throughout the human body. It helps different systems communicate and respond as conditions change.

Although its name sounds as though it comes from cannabis, the endocannabinoid system is a natural part of the body. People have an ECS whether or not they have ever used hemp or cannabis. In fact, scientists discovered the system while investigating how THC interacts with the body.

The ECS includes cannabinoid receptors, compounds made by the body called endocannabinoids, and enzymes that create and break down those compounds. Together, these components participate in signaling related to sleep, mood, appetite, memory, energy balance and many other everyday processes.

Understanding the endocannabinoid system also helps explain why CBD, THC and rare cannabinoids can produce different experiences even though they come from the same plant.

What Does the Endocannabinoid System Do?

The endocannabinoid system helps the body maintain balance as internal and external conditions change. Scientists call this ongoing process homeostasis.

Homeostasis does not mean that the body remains in one fixed state. It means that the body continually makes adjustments. Body temperature, appetite, alertness and sleep patterns all shift throughout the day. The ECS is one of several major signaling systems involved in coordinating these changes.

Researchers continue to study the ECS and its role in:

• Sleep and wake cycles

• Mood and emotional processing

• Appetite and digestion

• Learning and memory

• Motivation and reward

• Energy balance and metabolism

• Sensory processing

• Movement and coordination

• Responses to everyday stress

The ECS does not work alone. It communicates with other signaling systems throughout the brain and body, which is one reason cannabinoid science is both fascinating and complex.

What Are the Three Main Parts of the Endocannabinoid System?

The endocannabinoid system has three primary components:

1. Endocannabinoids: signaling compounds produced by the body

2. Cannabinoid receptors: sites that receive and respond to those signals

3. Enzymes: proteins that make endocannabinoids when needed and break them down after they have done their job

These components form a responsive system rather than a storehouse of compounds waiting to be released. Endocannabinoids are generally produced as needed and used locally before enzymes clear them away.

What Are Endocannabinoids?

Endocannabinoids are molecules naturally made within the body. The prefix “endo” means “within,” distinguishing endocannabinoids from phytocannabinoids—the cannabinoids produced by plants.

The two best-studied endocannabinoids are:

• Anandamide, also known as AEA

• 2-arachidonoylglycerol, usually shortened to 2-AG

Both can interact with cannabinoid receptors, but they are not identical and do not always send the same signals.

What Is Anandamide?

Anandamide is one of the first endocannabinoids scientists identified. Its name comes from ananda, a Sanskrit word associated with happiness or bliss.

Anandamide acts as a signaling molecule and can interact with CB1 and CB2 receptors as well as other targets. It is produced when needed and is generally broken down quickly, primarily by an enzyme called fatty acid amide hydrolase, or FAAH.

Researchers are still investigating how anandamide signaling changes in response to activities, surroundings and individual biology. It is sometimes called the “bliss molecule,” but that nickname simplifies a much broader and more nuanced role.

What Is 2-AG?

2-AG is another major endocannabinoid and is found at higher levels in the body than anandamide. It can activate both CB1 and CB2 receptors and participates in communication between cells throughout the nervous system and elsewhere in the body.

After 2-AG sends its signal, it is broken down primarily by an enzyme called monoacylglycerol lipase, or MAGL.

Anandamide and 2-AG are often discussed together, but the body makes, uses and clears them through different pathways. Scientists study both to understand the wider endocannabinoid system.

What Are Cannabinoid Receptors?

Receptors are proteins located on or within cells. They receive chemical messages and help the cell respond. CB1 and CB2 are the two best-known cannabinoid receptors.

Both belong to a large family called G protein-coupled receptors. When an endocannabinoid or another compatible molecule interacts with one of these receptors, it can change the messages being sent within the cell.

What Are CB1 Receptors?

CB1 receptors are especially abundant in the brain and central nervous system, although they are also present in other parts of the body.

Their location helps explain why CB1 signaling is associated with processes involving memory, appetite, movement, sensory perception, mood and the sleep-wake cycle. THC interacts strongly with CB1 receptors, producing the intoxicating experience for which THC is known.

What Are CB2 Receptors?

CB2 receptors are distributed more widely in peripheral tissues and are especially associated with cells involved in the body's defense and maintenance systems. Researchers have also identified CB2 receptors within the nervous system, although their distribution differs from that of CB1 receptors.

The common shorthand that CB1 receptors are only in the brain and CB2 receptors are only in the body is therefore an oversimplification. Both receptor types can be found in multiple locations, and research continues to clarify what they do.

What Do ECS Enzymes Do?

Enzymes help control how long endocannabinoid signals last. Some enzymes participate in producing endocannabinoids, while others break them down after use.

Two important examples are:

• FAAH, which is primarily associated with breaking down anandamide

• MAGL, which is primarily associated with breaking down 2-AG

This rapid create-use-breakdown cycle allows endocannabinoid signaling to respond to changing circumstances. It also makes the ECS different from systems in which signaling compounds may be produced in one location, stored and later released elsewhere.

How Does the Endocannabinoid System Work?

The ECS often works “on demand.” When a cell needs to adjust a signal, endocannabinoids can be produced from components of the cell membrane. They travel a short distance, interact with receptors and are then broken down by enzymes.

In the nervous system, endocannabinoids can travel backward across the space between two nerve cells. This is called retrograde signaling.

Most chemical messengers move from a sending cell to a receiving cell. In retrograde endocannabinoid signaling, the receiving cell can send an endocannabinoid message back toward the sending cell. This feedback can influence how much of another messenger is released.

In simple terms, the ECS can act like a fine-tuning system for cellular communication. The exact response depends on where the receptors are located, which signaling molecules are present and what else is happening in the body at that time.

Endocannabinoids vs. Phytocannabinoids

Endocannabinoids and phytocannabinoids are related, but they come from different sources.

• Endocannabinoids are produced within the body. Anandamide and 2-AG are the best-known examples.

• Phytocannabinoids are produced by plants. THC, CBD, CBG, CBN, CBC, THCV and CBDV are examples found in hemp or cannabis.

Some phytocannabinoids can interact directly with cannabinoid receptors. Others influence the ECS more indirectly or interact with additional molecular targets outside the classic CB1 and CB2 pathways.

This is why it is not accurate to say that every cannabinoid works in the same way—or that every effect associated with a cannabinoid is caused solely by the ECS.

How Do Cannabinoids Interact With the Endocannabinoid System?

Cannabinoids have different chemical structures and different patterns of activity. Some bind readily to cannabinoid receptors, while others have low affinity for CB1 and CB2 and work through more indirect pathways.

The amount used, the formulation, the presence of other cannabinoids and a person's individual response can all influence the experience.

THC and the Endocannabinoid System

Delta-9-tetrahydrocannabinol, or THC, interacts directly with cannabinoid receptors and has a particularly strong relationship with CB1 receptors. This activity produces THC's recognizable intoxicating effects and can also influence perception, appetite, mood and relaxation.

THC's resemblance to the body's own cannabinoid signals allows it to activate some of the same receptors, but THC is not identical to anandamide or 2-AG. Its effects and duration can therefore be different from those of endocannabinoids made by the body.

CBD and the Endocannabinoid System

Cannabidiol, or CBD, does not strongly activate CB1 receptors in the way THC does and is not intoxicating. Its activity is more indirect and involves several molecular pathways.

Researchers have studied CBD's relationship with cannabinoid receptor signaling, enzymes and non-cannabinoid targets. This broader activity is one reason the phrase “CBD binds to cannabinoid receptors” does not tell the full story.

CBD gummies and oils are often used to promote calm, balance, and in products for stress relief.

CBG and the Endocannabinoid System

CBG, or cannabigerol, is a non-intoxicating rare cannabinoid. It can interact with components of the cannabinoid system as well as other receptor families.

CBG is also known as the “mother cannabinoid” because its acidic precursor, CBGA, is used by the plant to make the precursors of several other cannabinoids. This describes CBG's role within the plant; it does not mean that CBG creates other cannabinoids after consumption.

CBG is often used in products for muscle and soreness relief as it has been found to reduces occassional swelling, stiffness and phyiscal discomfort. 

CBN and the Endocannabinoid System

CBN, or cannabinol, forms as THC changes with time, heat and exposure to oxygen. It can interact with cannabinoid receptors but is chemically and experientially distinct from THC.

CBN is frequently included in nighttime cannabinoid formulations and sleep products designed for relaxation and deep sleep. Research into CBN as an individual cannabinoid is still developing, and many products combine it with CBD, THC or both. 

CBC and the Endocannabinoid System

CBC, or cannabichromene, is a non-intoxicating rare cannabinoid. Some research suggests that it affects levels of FAAH and may increase levels of the brain's "bliss" molecule anandamide. It does not appear to strongly activate CB1 receptors. Researchers are studying its activity at other molecular targets and its relationship with the body's own cannabinoid signaling.

CBC is often featured in cannabinoid formulations designed around an uplifted, mood enhancing, positive experience. CBC is often paired with THC and CBD to enhance the dreamy feeling in products designed for mood enhancement. Because CBC does not produce the classic THC high, it can also be used in THC-free products.

THCV and the Endocannabinoid System

THCV, or tetrahydrocannabivarin, has a name and molecular structure similar to THC, but the two cannabinoids can behave differently.

THCV's activity can vary with concentration and context. At lower and moderate levels, it may reduce some CB1 signaling rather than activate the receptor in the same manner as THC. However, at very high levels, its behavior may change. This distinctive activity has contributed to interest in THCV gummies and oils for daytime formulations centered on energy and focus as well as products for appetite control.

CBDV and the Endocannabinoid System

CBDV, or cannabidivarin, is a non-intoxicating cannabinoid related to CBD. Like CBD, it does not produce the classic THC high and appears to interact with several signaling pathways rather than acting as a strong CB1 activator.

CBDV is found naturally in some varieties of cannabis and hemp, generally in small amounts. 

It is featured in products for social ease and irritability and may also enhance memory by offering stress resilience.

Why Do Different Cannabinoids Feel Different?

Cannabinoids can feel different because they do not all interact with the same receptors in the same way.

Their effects can also be influenced by:

• The amount of each cannabinoid

• Whether the formula contains THC

• The ratio of cannabinoids within the formula

• The type of product and how it is used

• The time of day

• Individual metabolism and sensitivity

• Prior experience with cannabinoids

• Food and other products consumed around the same time

For example, THC strongly activates CB1 receptors, while CBD has a more indirect pattern of activity. THCV may behave differently at different concentrations, and cannabinoids such as CBC and CBDV are being studied across several molecular pathways.

The ECS provides part of the explanation, but cannabinoids can interact with targets outside the classic endocannabinoid system as well. For a closer comparison, read Why Do Cannabinoids Feel So Different?

What Is the Entourage Effect?

The entourage effect is the idea that cannabinoids, terpenes and other naturally occurring hemp compounds may create a different overall experience together than a single compound used alone.

This term is often used when discussing full-spectrum and broad-spectrum hemp products:

• Full-spectrum hemp extract contains multiple hemp compounds, including a legally compliant amount of THC.

• Broad-spectrum hemp extract contains multiple hemp compounds but is formulated without detectable THC.

• Cannabinoid isolate contains one isolated cannabinoid without the broader range of plant compounds.

The entourage effect remains an active area of research. It should not be interpreted to mean that more cannabinoids will always produce a stronger or more desirable experience. The specific combination, amount and individual all matter.

Does Everyone Have an Endocannabinoid System?

Yes. The endocannabinoid system is a normal biological system found in humans and throughout the vertebrate animal kingdom. It is not created by taking CBD or using cannabis.

The body naturally produces endocannabinoids whether or not a person ever consumes phytocannabinoids. Plant cannabinoids can interact with this existing signaling network, but they do not give the body an ECS.

Can You “Activate” or “Boost” the Endocannabinoid System?

The ECS is already active. It constantly produces and clears signals in response to changing conditions.

Phrases such as “activate your ECS” or “boost your endocannabinoid system” are common online, but they can be misleading. A particular cannabinoid may influence one part of endocannabinoid signaling without universally increasing the activity of the entire system.

Everyday factors including movement, sleep, food, stress and social interaction have also been studied in connection with endocannabinoid levels. Researchers are still learning how meaningful and consistent these changes are.

What Is Endocannabinoid Tone?

“Endocannabinoid tone” is a research term describing the overall state of endocannabinoid signaling. It can include:

• Levels of anandamide and 2-AG

• The number and sensitivity of cannabinoid receptors

• The activity of enzymes such as FAAH and MAGL

Endocannabinoid tone is not one simple score, and it can vary by tissue and circumstance. Scientists use the concept to study how different parts of the ECS work together.

What Is Endocannabinoid Deficiency?

Clinical endocannabinoid deficiency is a scientific hypothesis proposing that unusually low or altered endocannabinoid signaling could be associated with certain patterns in the body.

It is not a simple deficiency that can be identified through an ordinary consumer test, and it should not be treated as a settled diagnosis. More research is needed to understand whether the hypothesis applies consistently and how endocannabinoid signaling could be measured meaningfully in people.

When Was the Endocannabinoid System Discovered?

The modern understanding of the ECS emerged gradually:

• Scientists identified a cannabinoid receptor now known as CB1 in the late 1980s.

• CB1 was cloned in 1990, allowing researchers to study it more precisely.

• Researchers identified anandamide in 1992.

• The CB2 receptor was cloned in 1993.

• 2-AG was identified as an endocannabinoid shortly afterward.

These discoveries showed that the body has its own cannabinoid-like signaling molecules and the receptors that respond to them. They also opened a much larger field of research into cannabinoids made by the body and those found in plants.

Common Questions About the Endocannabinoid System

Is the endocannabinoid system real?

Yes. CB1 and CB2 receptors, anandamide, 2-AG and their metabolic enzymes have been identified and studied extensively. “Endocannabinoid system” is the scientific name for this interconnected signaling network.

Is the endocannabinoid system the same as the nervous system?

No. The ECS operates within the nervous system and in many other tissues, but it is not the entire nervous system. It is one signaling network that communicates with several other systems.

Do CBD and THC work the same way?

No. THC directly activates cannabinoid receptors, particularly CB1, and can be intoxicating. CBD does not strongly activate CB1 and is not intoxicating. It has a more indirect and wide-ranging pattern of activity.

Are CB1 receptors only in the brain?

No. CB1 receptors are especially abundant in the brain and central nervous system, but they also occur elsewhere in the body.

Are CB2 receptors only in the immune system?

No. CB2 receptors are strongly associated with immune cells and peripheral tissues, but they have also been detected in parts of the nervous system.

Are all cannabinoids intoxicating?

No. THC is intoxicating, but CBD, CBG, CBN, CBC and CBDV do not produce the classic THC high. THCV can have different activity depending on amount and context and is generally used very differently from THC.

Is the ECS fully understood?

No. Its core receptors, endocannabinoids and enzymes are well established, but researchers continue to investigate how the system changes across tissues, individuals and circumstances. Cannabinoids may also interact with targets that are not formally part of the classic ECS.

Learning Which Cannabinoids Are Right for You

Learning about the endocannabinoid system is a useful first step, but receptor science alone cannot predict exactly how a particular product will feel for every person.

Some people begin with a familiar cannabinoid such as CBD. Others explore a rare cannabinoid based on the type of experience they are seeking, such as CBN in a nighttime routine, THCV during the day or CBC in a mood-focused formula.

Rare Cannabinoid Company creates precisely measured formulas featuring CBD, THC and rare cannabinoids including CBG, CBN, CBC, THCV and CBDV. You can also take our one-minute Cannabinoid Finder Quiz to compare options based on your preferred experience, product format and amount of THC.

The Endocannabinoid System: A Growing Field of Discovery

The discovery of the endocannabinoid system changed the scientific understanding of how cannabinoids interact with the body. The ECS is not a cannabis-created system; it is an internal communication network with its own receptors, signaling compounds and enzymes.

Anandamide, 2-AG, CB1, CB2, FAAH and MAGL form the best-known foundation of this network. Plant cannabinoids can influence it in different ways, helping explain why CBD, THC and rare cannabinoids are not interchangeable.

As cannabinoid research continues, scientists are building a more detailed picture of how the ECS works—and how individual cannabinoids interact with this remarkably responsive system.

Scientific References

1. Lu H-C, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biological Psychiatry. 2016.

2. Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences. 2018.

3. Blankman JL, Cravatt BF. Chemical Probes of Endocannabinoid Metabolism. Pharmacological Reviews. 2013.

4. Pertwee RG, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands. Pharmacological Reviews. 2010.

5. Lu D, Potter DE. Cannabinoids and the Cannabinoid Receptors: An Overview. Handbook of Experimental Pharmacology. 2017.