Endocannabinoid System Guide

The endocannabinoid system, or ECS, is a network of chemical signals, receptors, and enzymes in your body. It works whether or not you use cannabis. The name reflects how researchers discovered it while studying cannabinoids.

The ECS helps cells adjust their activity. Understanding that process can explain some effects of cannabis, but it does not show that a particular product will treat a condition.

The body's own cannabinoid signals

“Endo” means within. Endocannabinoids are molecules your body makes, rather than compounds obtained from a plant. Two of the best-studied are anandamide and 2-arachidonoylglycerol, usually called 2-AG.

Anandamide (AEA): A fat-derived signaling molecule that can activate cannabinoid receptors. Its identification helped establish that the body makes its own cannabinoid signals. See the original anandamide discovery study.
2-AG: Another fat-derived signal that acts at cannabinoid receptors. It plays an important role in communication between nerve cells.

These signals are made and broken down as part of ongoing cell activity. They are not simply a stored supply of “natural THC.” NIH's cannabinoid research meeting summary (PDF) describes their roles and the questions researchers are studying.

CB1 receptors

Receptors are proteins that respond to chemical signals. CB1 receptors are abundant in the nervous system, including the brain, and also occur elsewhere in the body. Activating them can change how nerve cells release other signaling chemicals.

THC acts at CB1 receptors, helping explain its effects on perception, memory, and coordination. That is different from the body's brief, local endocannabinoid signaling. CDC describes the effects of cannabis on attention, memory, and movement in its cannabis and brain health overview.

CB2 receptors

CB2 receptors are strongly associated with immune cells. Their activity is studied in inflammation and immune signaling. Calling CB2 a “peripheral receptor” is a useful historical shorthand, but it should not be read as a strict rule that CB2 never occurs in the nervous system.

The original CB2 receptor study helped distinguish it from CB1. Knowing that a compound acts at CB2 does not, by itself, show that it treats inflammation in people.

Enzymes that end the signal

Enzymes help make endocannabinoids and break them down. The breakdown step limits how long a signal lasts.

FAAH: Fatty acid amide hydrolase is an important enzyme for breaking down anandamide. Early enzyme research established this activity.
MAGL: Monoacylglycerol lipase, also called MGL, is an important enzyme for breaking down 2-AG. See research on its role in ending 2-AG signaling.

These are important parts of the system, not a complete list of every enzyme or pathway involved.

How cells use these signals

At some connections between nerve cells, endocannabinoids provide feedback. A receiving cell produces a signal that travels back to the sending cell. By activating cannabinoid receptors there, it can reduce further release of a neurotransmitter, the chemical carrying the message between cells.

This is called retrograde signaling. Laboratory research on hippocampal synapses demonstrated this process. It is one way the ECS adjusts communication, rather than a single switch that turns all brain activity up or down.

Where THC and CBD fit

THC: A plant cannabinoid that activates cannabinoid receptors, including CB1. Its effects depend on the amount, method of use, and individual, not just the presence of a receptor.
CBD: CBD does not act like THC at CB1. A cell study found that it could modify CB1 signaling; CBD also has actions outside this receptor. A laboratory mechanism does not establish what a retail product will do.

CBD should not be assumed to cancel THC's effects. In a controlled study of oral THC with a high dose of CBD, the combination produced stronger effects than THC alone.

For individual compounds and their evidence, see the Cannabis Cannabinoid Guide.

What the science does and does not tell us

Finding a receptor or explaining a mechanism is a starting point for research. It does not establish that activating that receptor is beneficial in every situation, or that more activation is better. Benefits and adverse effects have to be studied in people using a defined product and a defined outcome.

Claims that a product “balances” or “supports” the ECS need specific evidence about what was measured and what improved. The phrase alone does not identify a demonstrated medical benefit.

FDA explains how cannabis-related products are evaluated in its research and drug approval overview. For broader health information, see CDC's cannabis health effects resources.

Official resources

For definitions of related terms, return to the Cannabis Glossary.