Cannabinoid Report: 2-AG

October 15, 2019

2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid – one of many naturally occurring cannabinoids produced by the mammalian body (2-AG has even been found in cow’s milk and human breast milk.) 2-AG was the second endocannabinoid to be discovered, after anandamide; similarly, it is probably the second most studied endocannabinoid following anandamide. Although researchers from Teikyo University in Tokyo, Japan were the first to describe 2-AG in 1994-1995, Dr. Raphael Mechoulam and his student, Shimon Ben-Shabat, had discovered it well before then. As well, Mechoulam was the first to successfully isolate the compound in the canine gut in 1995. The combination of these separate discoveries helped to paint a full picture of the characteristics of 2-AG.

Indeed, 2-AG is a full agonist for the body’s CB receptors and is the primary ligand for the body’s CB2 receptor. It has mediating effects on cannabis’s active components. Like anandamide, 2-AG is also a derivative of the fatty acid arachidonic acid. Also similar to anandamide, 2-AG is synthesized on demand when it is needed for homeostasis rather than being stored. However, unlike anandamide, 2-AG occurs in very high levels in the body’s central nervous system. Research shows that “2-AG has been found present in the brain at concentrations 170 times greater than AEA” and that “2-AG has been shown to mediate the retrograde signaling of the endocannabinoid system in the brain.”


2-AG is the most abundant endogenous cannabinoid in the body, and it is one of the most well-studied endogenous cannabinoids, so there are many reasons to believe that it has useful medical benefits. Several studies have concluded that 2-AG displays both anti-inflammatory and neuroprotective properties. For example, in 2001, one study concluded that 2-AG is an effective neuroprotectant after brain injury. As well, because 2-AG primarily binds to the CB2 receptor, and because the CB2 receptor is associated with its anti-inflammatory properties, 2-AG may be useful in regulating inflammation.

2-AG may also be useful in bone formation. The CB2 receptor is thought to be potentially helpful in correcting infertility, which renders 2-AG promising. 2-AG also triggers REM, which suggests that the endocannabinoid could be useful in treating various sleep disorders. As well, research shows that 2-AG controls both neuropathic pain and mechanical hyperalgesia for some patients; this research suggests that 2-AG may be an effective tool in managing and reducing pain.


There is little known as to the negative side effects of 2-AG, although its promising medical benefits may not be effective for every individual.