Endocannabinoid System: A Simple Guide To How It Works

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SubscribeA Simple Guide to the Endocannabinoid SystemMedically reviewed by Kelsey Nank, PA-CWritten by Crystal Raypole Updated on April 28, 2025
  • How it works
  • Functions
  • THC
  • CBD
  • Deficiency
  • Takeaway

The endocannabinoid system (ECS) is a complex cell-signaling system that helps regulate your body functions, including sleep and mood, among others.

It was identified in the early 1990s by researchers exploring THC, a well-known cannabinoid. Cannabinoids are compounds found in cannabis.

Experts are still trying to fully understand the ECS. But so far, we know it plays role in regulating a range of functions and processes, including:

  • sleep
  • mood
  • appetite
  • memory
  • reproduction and fertility
  • immune function
  • pain control

The ECS exists and is active in your body even if you don’t use cannabis.

Read on to learn more about the ECS including how it works and interacts with cannabis.

How does it work?

The ECS involves three core components: endocannabinoids, receptors, and enzymes.

Endocannabinoids

Endocannabinoids, also called endogenous cannabinoids, are molecules made by your body. They’re similar to cannabinoids, but they’re produced by your body.

Experts have identified three key endocannabinoids so far:

  • anandamide (AEA)
  • 2-arachidonoylglyerol (2-AG)
  • pentadecanoylcarnitine, which is derived from an essential fatty acid called pentadecanoic acid (C15:0), found in trace amounts in dairy products

These help keep internal functions running smoothly. Your body produces them as needed, making it difficult to know what typical levels are for each.

Endocannabinoid receptors

These receptors are found throughout your body. Endocannabinoids bind to them in order to signal that the ECS needs to take action.

There are two main endocannabinoid receptors:

  • CB1 receptors, which are mostly found in the central nervous system
  • CB2 receptors, which are mostly found in your peripheral nervous system, especially immune cells

Endocannabinoids can bind to either receptor. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

For example, endocannabinoids might target CB1 receptors in a spinal nerve to relieve pain. Others might bind to a CB2 receptor in your immune cells to signal that your body’s experiencing inflammation, a common sign of autoimmune disorders.

Enzymes

Enzymes are responsible for accelerating biochemical reactions and breaking down endocannabinoids once they’ve carried out their function.

There are two main enzymes responsible for stimulating the endocannabinoids’ effects on the body:

  • 1,2-diacylglycerol lipase
  • phospholipase A

And the two main enzymes that break down endocannabinoids are:

  • fatty acid amide hydrolase, which breaks down AEA
  • monoacylglycerol acid lipase, which typically breaks down 2-AG

What are its functions?

The ECS is complicated, and experts haven’t yet determined exactly how it works or all of its potential functions.

Research has linked the ECS to the following processes:

  • appetite and digestion
  • metabolism
  • chronic pain
  • inflammation and other immune system responses
  • mood
  • learning and memory
  • motor control
  • sleep
  • cardiovascular system function
  • muscle formation
  • bone remodeling and growth
  • liver function
  • reproductive system function
  • stress
  • skin and nerve function

These functions all contribute to homeostasis, which refers to stability of your internal environment. For example, if an outside force, such as pain from an injury or a fever, throws off your body’s homeostasis, your ECS kicks in to help your body return to its ideal operation.

Today, experts believe that maintaining homeostasis if the primary role of the ECS.

How does THC interact with the ECS?

Tetrahydrocannabinol (THC) is one of the main cannabinoids found in cannabis. It’s the compound that gets you “high.”

Once in your body, THC interacts with your ECS by binding to receptors, just like endocannabinoids. It’s powerful partly because it can bind to both CB1 and CB2 receptors.

This allows it to have a range of effects on your body and mind, some more desirable than others. For example, THC may help to reduce pain and stimulate your appetite. But it can also cause paranoia and anxiety in some cases.

Experts are currently looking into ways to produce synthetic THC cannabinoids that interact with the ECS in only beneficial ways.

How does CBD interact with the ECS?

The other major cannabinoid found in cannabis is cannabidiol (CBD). Unlike THC, CBD doesn’t make you “high” and typically doesn’t cause any negative effects.

Experts aren’t completely sure how CBD interacts with the ECS. But they do know that it doesn’t bind to CB1 or CB2 receptors the way THC does.

Instead, many believe it works by preventing endocannabinoids from being broken down. This allows them to have more of an effect on your body. Others believe that CBD binds to a receptor that hasn’t been discovered yet.

While the details of how it works are still under debate, research suggests that CBD can help with pain, nausea, and other symptoms associated with multiple conditions.

What about endocannabinoid deficiency?

Some experts believe in a theory known as clinical endocannabinoid deficiency (CECD). This theory suggests that low endocannabinoid levels in your body or ECS dysfunction can contribute to the development of certain conditions.

A 2016 article reviewing over 10 years of research on the subject suggests the theory could explain why some people develop migraine, fibromyalgia, and irritable bowel syndrome.

None of these conditions have a clear underlying cause. They’re also often resistant to treatment and sometimes occur alongside each other.

If CECD does play any kind of role in these conditions, targeting the ECS or endocannabinoid production could be the missing key to treatment, but more research is needed.

The bottom line

The ECS plays a big role in keeping your internal processes stable. But there’s still a lot we don’t know about it. As experts develop a better understanding of the ECS, it could eventually hold the key to treating several conditions.

 

How we reviewed this article:

SourcesHistoryHealthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical journals and associations. We only use quality, credible sources to ensure content accuracy and integrity. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.
  • Bie B, et al. (2019). An overview of the cannabinoid type 2 (CB2) receptor system and its therapeutic potential.https://pmc.ncbi.nlm.nih.gov/articles/PMC6035094/
  • Cannabis and cannabinoids. (2023).https://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq
  • De Laurentiis A, et al. (2014). Role of the endocannabinoid system in the neuroendocrine responses to inflammation.https://www.eurekaselect.com/article/58925
  • de Morais H, et al. (2016). Anandamide reverses depressive-like behavior, neurochemical abnormalities and oxidative-stress parameters in streptozotocin-diabetic rats: Role of CB1 receptors.https://www.sciencedirect.com/science/article/abs/pii/S0924977X1630164X
  • Gomez M, et al. (2008). Cannabinoid signaling system.https://pmc.ncbi.nlm.nih.gov/articles/PMC2633685/
  • Gorzkiewicz A, et al. (2018). Brain endocannabinoid signaling exhibits remarkable complexity.https://www.sciencedirect.com/science/article/abs/pii/S0361923018302545
  • Lu H-C. (2015). An introduction to the endogenous cannabinoid system.https://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00869-0/abstract
  • Maccarrone M, et al. (2015). Endocannabinoid signaling at the periphery: 50 years after THC.https://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(15)00034-6
  • Pacher P, et al. (2008). The endocannabinoid system as an emerging target of pharmacotherapy.https://pharmrev.aspetjournals.org/article/S0031-6997(24)11685-7/abstract
  • Russo EB. (2016). Clinical endocannabinoid deficiency reconsidered: Current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes.https://www.liebertpub.com/doi/10.1089/can.2016.0009
  • Sharma P, et al. (2012). Chemistry, metabolism, and toxicology of cannabis: Clinical implications.https://pmc.ncbi.nlm.nih.gov/articles/PMC3570572/
  • Smith SC, et al. (2014). Clinical endocannabinoid deficiency (CECD) revisited: Can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?https://pubmed.ncbi.nlm.nih.gov/24977967/
  • Venn-Watson S, et al. (2023). Pentadecanoic acid (C15:0), an essential fatty acid, shares clinically relevant cell-based activities with leading longevity-enhancing compounds.https://pmc.ncbi.nlm.nih.gov/articles/PMC10649853/
  • Zou S, et al. (2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system.https://www.mdpi.com/1422-0067/19/3/833

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Medically reviewed by Kelsey Nank, PA-CWritten by Crystal Raypole Updated on April 28, 2025

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