The canonical triterpene amyrin was recently suggested to bind to CB1 receptors and to significantly mediate cannabimimetic effects in animal models of pain (Pain, 2011 Aug;152(8):1872-87). Andrea Chicca and Janine Marazzi in my lab now show that this molecule does NOT directly interact with CB receptors but inhibits the breakdown of the major endocannabinoid 2-AG. Thus, it is an indirect ligand at CB receptors, which may explain, at least in part, its analgesic and antiinflammatory effects. Interestingly, amyrin weakly targets both MAGL and ABHD hydrolases (partial inhibition) but the effect of this on 2-AG levels in brain tissue is superadditive. Since amyrin is a major constituent of many antiinflammatory and analgesic medicinal plants, we speculate that its presence is fundamentally involved in their pharmacological action.