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What is the Endocannabinoid System?

By Caitlin Kenney
Updated May 23, 2024
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The endocannabinoid system (ECS) is a set of signaling molecules in the central and peripheral nervous system that helps regulate processes of the body such as appetite, pain, mood, and memory. A signaling molecule is a chemical that passes information from cell to cell. In the endocannabinoid system, these molecules are primarily signaling lipids called endocannabinoids, fatty molecules that bind to receptor proteins to trigger a response. The chemical make-up of endocannabinoids and the responses they elicit are mimicked closely by the drug cannabis, which is sometimes prescribed to trigger an increase in appetite, a lessening of pain, and a lifting of mood.

An endocannabinoid is an example of a ligand, or a molecule that binds to proteins in order to generate a signal response. In the endocannabinoid system, these ligands exist within cells in the central and peripheral nervous system. The nervous system is a network of signaling tissues that gathers sensory input, processes this information, and then allows the body to make a coordinated response to the stimuli. The sensory input can be internal or external to the body, sensing factors such as outside temperature, body temperature, blood acidity, blood pressure, sounds, sights, smells, and pressure on the body. The central nervous system includes only the brain and spinal cord, while the peripheral nervous system encompasses all nerve cells outside of the brain and spinal cord.

The endocannabinoid system involves two main ligands, anandamide (AEA) and 2-arachidonoylgycerol (2-AG), which are produced and released inside the body in response to an electrical impulse called a depolarization. It is thought that cells produce endocannabinoids as they are needed, rather than having a constant stock within the cell. The ligands are then released into the synapse, or the space between nerve cells, and taken into the next cell. The ligands then bind to two cannabinoid receptors, CB1 and CB2, in order to produce a response.

Anandamide prefers to bind with the CB1 receptor, which is mostly located in the central nervous system, but also found in some of the body tissues. The 2-AG endocannibinoid binds equally to both the CB1 receptor and the CB2 receptor, which is located in the peripheral nervous system. There is evidence of a third ligand called noladin ether, which binds more strongly to CB2, though there is debate over whether the substance can actually be called an endocannibinoid. Two other endocannabinoids called N-arachidonoyl-dopamine (NADA) and Virodhamine (EOE) have been discovered recently and bind more strongly to CB1 and CB2, respectively.

Both receptors are made of proteins, or chemical compounds composed of amino acid chains, that accept and respond to the release of ligands. These responses in the endocannabinoid system regulate several of the body’s processes, including the sensation of pain, appetite, mood, memory, learning movement skills, and the regulation of the nervous system. Because cannabis contains compounds called cannabinoids that are chemically similar to endocannabinoids, the introduction of cannabis into the body can produce some of the same responses.

In the 1980s, it was discovered that chemical compounds within cannabis bind to cannabinoid receptors within the nervous system, much in the same way that endocannabinoids bind to the cannabinoid receptors. The three principle cannabinoids present in cannabis are tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), but there are many such substances that interact with the endocannibinoid system. Those that bind to CB1 are thought to be responsible for the mood lifting and anti-convulsive qualities of the drug. The cannabinoids that bind to CB2 are thought to contribute to the anti-inflammatory, or anti-swelling, qualities of the drug that help to dull pain.

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Discussion Comments
By anon998485 — On Jun 19, 2017

After personally using extracted high content THC with low CBD content for 3 months my appetite became nonexistent. I lost approximately 20 lbs and my appetite didn't return for about two months.

By WaterSerpent — On Oct 19, 2014

@ Copper Salmon

It's a study I found in the US National Library of Medicine. I'm just really curious how it affects the metabolic regulation in the body. If it works for rats, why not people?

By CopperSalmon — On Oct 18, 2014

@ Water Serpent

I'm not sure what study you're referring too, but the article said that CB1 is responsible for mood enhancement and is an anticonvulsant. A study by Guzman, who won the Nobel Prize, found that THC oil high in CBD killed lung cancer cells in rats. I think there's a lot we still don't know about THC, CBD, and CBN; how each interacts with our endocannabinoid system. What study are you referring too?

By WaterSerpent — On Oct 18, 2014

There was a study done concerning SR1411716, a CB1 receptor antagonist and the results were surprising. Food intake and weight were both reduced in obese rats. I find that surprising because cancer patients use medical marijuana for the opposite effect. Does anyone know more about this particular CB1 receptor antagonist?

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