2-Arachidonyl glyceryl ether, often referred to as noladin ether or 2-AGE, is a stable analog of the endogenous cannabinoid 2-AG. It was discovered in 2000 by Lumír Hanuš and his colleagues (Saleh Abu-Lafi, Ester Fride, Aviva Breuer, Zvi Vogel, Deborah E. Shalev, Irina Kustanovich, and Raphael Mechoulam) at the Hebrew University of Jerusalem, in Israel. Its isolation and synthesis were described by that team in 2001 – the endocannabinoid was isolated from porcine brain and its structure was determined by mass spectrometry and nuclear magnetic resonance spectrometry. 2-AGE was the third endocannabinoid to be discovered, after anandamide and 2-AG. 2-AGE is a strong agonist for the CB1 receptor, whereas it binds only weakly to the CB2 receptor. 2-AGE is also a partial agonist for the TRPV1 receptor.
There has been significantly less research conducted regarding the medical effects of 2-AGE than there has been for other endogenous cannabinoids. Indeed, the team that initially discovered 2-AGE believes that, because 2-AGE binds poorly to the CB2 receptor, it may have a narrower profile of physiological effects than that of anandamide or 2-AG. However, 2-AGE may be useful in certain CB1-based functions of the body’s endocannabinoid system, though those functions were not specified in the team’s report. As well, the team notes that ethers, such as 2-AGE, are stable in vivo (unlike anandamide or 2-AG) – 2-AGE has an endogenous half-life of hours as opposed to mere minutes. Because of this impressive level of stability, 2-AGE may be useful in some drug development. These observations can be found in the team’s 2001 report.
One study reported that 2-AGE, among other endocannabinoids, has raised interest as a potentially anticancerogenic substance. 2-AGE can also induce sedation, can reduce ocular pressure, and demonstrates modest antinociceptive (anti-pain) activity in vivo for mice. 2-AGE may also cause intestinal immobility and “attenuates sensory neurotransmission in rat mesenteric arteries via GPR55.”
Because 2-AGE is not as potent as other endocannabinoids, it has not been studied quite as extensively. Therefore, little is known as to the negative side effects of 2-AGE or as to its long-term effects.