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Cannabinoid Clinic: 2-AG

Updated: Dec 7, 2022

Welcome to Cannabinoid Clinic, an education project powered by Higher Learning LV. This series provides cannabis and hemp industry professionals with easily digested cannabinoid profiles that ask little of your time—but provide plenty of science-based information.


There are two categories of cannabinoids: Phytocannabinoids and endocannabinoids. Phytocannabinoids are those produced by cannabis/marijuana/hemp, while endocannabinoids are made by the human body. This series covers both.

2-AG molecular structure


What is 2-AG?

The two major endocannabinoids produced by the human endocannabinoid system (ECS) are 2-AG and anandamide. 2-AG is short for 2-arachidonoylglycerol and was discovered in 1994 by Japanese researchers at Teikyo University. Raphael Mechoulam and his student Shimon Ben-Shabat at Hebrew University first isolated 2-AG from the gut of a dog in 1995, three years following the discovery of the endocannabinoid anandamide.


"2-AG has been found to be 170 times more abundant in the brain than anandamide. 2-AG is also found in human breast milk and cow's milk."

This endocannabinoid is intimately involved in a number of bodily processes, including the regulation of appetite, the immune system, and pain.


Levels of both anandamide and 2-AG can be increased via a variety of mechanisms, including regular exercise. 2-AG has been found to be 170 times more abundant in the brain than anandamide. 2-AG is also found in human breast milk and cow's milk (more evidence of the existence of an ECS in creatures other than humans). Both anandamide and 2-AG are synthesized on demand, when needed by the body, instead of being produced and stored, like some other endogenously produced molecules.


2-AG Fast Facts

  • Role: Results from phospholipids

  • Biosynthetic pathway: Phospholipids > 2-AG > arachidonic acid and glycerol

  • Psychoactivity: Non-psychoactive (but mood control)

  • Acidic precursor: n/a

  • Boiling point: n/a

  • Medical benefits: Reduced inflammation and neuroprotection


2-AG Medicinal Benefits

The endocannabinoid 2-AG has demonstrated a range of medicinal efficacies. Multiple peer-reviewed studies have revealed this endocannabinoid's anti-inflammatory and neuroprotective properties, including a potential role in the formation of bones and maintenance of reproductive fertility.


Based on its notable neuroprotective properties, 2-AG likely plays an important role in prevention of a number of common diseases of the brain, including dementia, Parkinson's disease, Alzheimer's disease, and Hungtinton's disease.


"Multiple peer-reviewed studies have revealed this endocannabinoid's anti-inflammatory and neuroprotective properties."

An October 2001 study entitled "An Endogenous Cannabinoid (2-AG) is Neuroprotective After Brain Injury" that was published in the journal Nature explored the potential neuroprotective role played by this endocannabinoid.


The study reported that "after injury to the mouse brain, 2-AG may have a neuroprotective role in which the cannabinoid system is involved." It found that mice which had suffered brain injuries featured "significantly elevated" levels of 2-AG.

Image courtesy Raphael Mechoulam


"We administered synthetic 2-AG to mice after [brain injury] and found significant reduction of brain oedema, better clinical recovery, reduced infarct volume, and reduced hippocampal cell death compared with controls," reported the study's authors. The research noted that 2-AG resulted in "significantly enhanced functional recovery," but that this benefit was dependent upon dose.


"2-AG after [brain injury] resulted in significant reduction of brain oedema, better clinical recovery, and reduced hippocampal cell death."

A 2006 study entitled "The Endocannabinoid 2-AG Protects the Blood–brain Barrier After Closed Head Injury and Inhibits mRNA Expression of Proinflammatory Cytokines" that was published in the journal Neurobiology of Disease and co-authored by Mechoulam explored "the effect of 2-AG on the blood–brain barrier (BBB) and the possible inhibition of the early expression of proinflammatory cytokines, which are implicated in BBB disruption."

The study reported that endocannabinoids are "involved in neuroprotection through numerous biochemical pathways" and that mouse brains release 2-AG after brain injury. In addition, the research noted that treatment with 2-AG "exerts neuroprotection via the central cannabinoid receptor CB1" and that this mechanism involved a reduction in inflammation.


"2-AG treatment resulted in a number of desirable outcomes, including decreasing inflammation and an augmentation of endogenous antioxidants."

The research discovered that 2-AG treatment in the test subjects resulted in a number of desirable outcomes, including decreasing proinflammatory cytokines and an augmentation of endogenous antioxidants. It concluded that "2-AG exerts neuroprotection in part by inhibition of the early (1–4 h) inflammatory response and augmentation of the brain reducing power."


How to Get 2-AG

Exercise. Or get hurt.


2-AG is rapidly produced by the human body in an on-demand manner, as it is needed. As the most common endocannabinoid present in the brain and central nervous system, it is always present, but volumes vary depending on the health and overall status of a person. Literally the best way to produce more 2-AG and gain its health benefits is to exercise on a regular basis.


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