Figure 3

A: The endocannabinoid AEA and related NAEs PEA and OEA are broken down by FAAH, 2-AG is primarily metabolized by MAGL. AEA is a ligand at CB₁, CB₂ and TRPV1 receptors and the nuclear receptor PPAR-α. OEA and PEA are ligands for PPAR-α. 2-AG is a ligand at CB₁and CB₂. Both AEA and 2-AG can be metabolized by COX2, LOX and CYP450 to form biologically active metabolites, some of which are ligands for CB₁, CB₂ and PPAR-α. B: Under pathological conditions, such as inflammatory or neuropathic pain, the presence of infiltrating immune cells or the activation of microglia provides another source of endocannabinoid synthesis and catabolism, as well as providing additional/or alternative receptor sites of action of the endocannabinoids, NAEs and their metabolites.