The endocannabinoid system is a functionally versatile, complex and wide-ranging system whose purpose is to balance and monitor all the processes that are going on in the body. The system ensures that everything from menstruation to wound healing happens on time and correctly, and it can be found in almost all living things.

Studies have found that the background of almost all diseases is some degree of disturbance in the functioning of the endocannabinoid system. This is called, somewhat erroneously, clinical cannabinoid deficiency because it is not always a matter of a lack of endocannabinoids, but sometimes also of their overproduction. (1)

The endocannabinoid system consists of three components. About endogenous cannabinoids, i.e. endocannabinoids, their corresponding receptors, i.e. cannabinoid receptors, and the disintegrating molecules of these two.

What the heck is 2-AG?

2-AG, or arachidonoylglycerol, is another of the most well-known endocannabinoids. It is composed of various membrane phospholipids and is a derivative of the polyunsaturated omega-6 fatty acid arachidonic acid. Arachidonic acid is formed in the body from linoleic acid and can be obtained as such from products of the animal kingdom. (1,2,3)

2-AG acts as an endogenous ligand for cannabinoid receptors and is a full agonist for both CB1 and CB2 cannabinoid receptors. (1,2,3)

Endocannabinoids are formed in one or more enzymatic steps and are then released outside the cell to attach to CB1 and CB2 receptors, as well as other receptors in the body. (1,2,3)

Is 2-AG a neurotransmitter?

Neurotransmitter is a general name for neurotransmitters in the brain. They are chemical molecules whose task is to transmit messages between neurons in the brain.

2AG is a signaling lipid in the central nervous system and a primary regulator of neurotransmitter release. (1,3)

Location

Since endocannabinoids are formed from essential fatty acids, their precursors are always available on the lipid membrane of the cell. Endocannabinoids are not stored in the body, but are made as needed where they are needed.

Endocannabinoids are everywhere in the body, but they are especially abundant in the brain. (1)

Disruptors

2-AG is mainly broken down by one, but at least three enzymes in total. The main decomposer is an enzyme called MAGL (monoacylglycerol lipase) (1,2,3).

Excess 2-AG endocannabinoids are broken down into arachidonic acid and glycerol (3).

2-AG’s duties

Being part of such a significant system, 2-AG naturally has many tasks in different parts of the body. On a general level, the endocannabinoid system balances all the basic functions of the body, such as appetite, sleep, memory, learning, etc., but both endocannabinoids have their own important functions in these processes. (1)

Mainly 2-AG affects the central and peripheral nervous system, where it is involved in e.g. to nerve flexibility and nervous excitability, but the activation of CB1 and CB2 receptors by 2-AG is also involved in several physiological processes. Among other things, inflammation, learning and memory, nerve protection, pain sensation and mood as well as stress, anxiety, addictions and reward behavior are dependent on CB1 and CB2 receptors activated by 2-AG. (2,3)

2-AG has also been found to be essential for the circulatory system.

Sources

1. Lu HC. and Mackie K.. 2015. An introduction to the endogenous cannabinoid system. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/. Referred on 9/11/2022.
2. Zou S. and Kumar U.. 2018. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/. Referred on 9/11/2022.
3. Baggelaar MP, Maccarrone M. and Stelt M.. 2018. 2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain. https://www.sciencedirect.com/science/article/pii/S0163782717300619. Referred on 9/11/2022.