Understanding 2-AG Research

Two types of cannabinoids exist on Planet Earth: Endocannabinoids that are manufactured by the human body (and a slew of vertebrates, including most mammals) and phytocannabinoids that are produced by the cannabis/hemp/marijuana plant species.

Interestingly, endocannabinoids are mimicked by phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD). Both sets of molecules provide a breadth of potential medicinal and wellness support roles, including anti-inflammatory, anticancer, and anti-anxiety benefits.

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

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

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.

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.

A 2019 study explored "the tumor microenvironment response to 2-AG in pancreatic cancer" and the compounds overall ability to prevent the spread of this fast-acting type of cancer that, according to the American Cancer Society, will result in nearly 60,000 positive diagnoses in 2020 and nearly 50,000 deaths during the same period.

2-AG molecular structure

The study reported that "2-AG inhibited pancreatic cancer cell proliferation in tumor bearing mice." The research found that the anticancer effects of this endocannabinoid were produced via direct, not indirect, mechanisms. The study concluded that its "findings support 2-AG exhibited direct antitumor effects via inhibiting pancreatic cancer proliferation."

A 2014 study investigated the ability of 2-AG to combat inflammation-based diseases involving neurodegeneration, including Alzheimer's disease and Parkinson's disease. Concluded the research report, "Previous studies show that...2-AG...reduces neuroinflammation...and prevents neurons from degenerating in an experimental...model of Parkinson’s disease."

A 2013 study revealed that 2-AG may play a role in achieving REM (deep) sleep, meaning it may be an effective therapeutic agent in the treatment of dozens of sleep disorders, including insomnia. "Our results indicate that 2-AG increases REM [sleep] through CB1 activation," concluded the study's authors.

According to another 2013 study, 2-AG may also be effective in managing pain. The study's authors concluded that "increasing plasma levels of 2-AG (up to ten fold of normal concentrations) mitigate mechanical pain sensitivity, while an absence of 2-AG increase leaves...patients with full-blown hyperalgesia [severe pain]."

A 2009 study documented the important role of CB2 receptors in immune function and provided "novel insights into the role of the CB2 [receptor] in maintaining a homeostatic immune balance." The study found that cannabinoid receptors "appear to play an important role in neuropathological diseases" and reported that CB1 receptors are "critical for the overall homeostatic balance and regulation of the central nervous system" while CB2 receptors were found to play "a functionally relevant role during neuroinflammation."

These mechanisms are potentially of value in the treatment of diseases involving neuroinflammation and neurodegeneration, including Alzheimer's disease, Parkinson's disease, and other forms of age-related dementia.

A 2001 study explored the ability of 2-AG to act as an effective neuroprotectant following brain injury. 2-AG binds with CB2 receptors, a characteristic that makes it effective in many disease states involving inflammation, including cancer, multiple sclerosis, fibromyalgia, arthritis, Crohn's disease, and Alzheimer's disease.