Altogether, our study provides evidence that subchronic URB597 administration counteracts iNOS expression and that increasing brain eCB signaling and, in particular, AEA signaling, can be a valuable strategy to reprogram a microglia phenotype whose hyperactivation has been identified as a pathogenetic factor underlying iNOS overactivation, in both AD-like models and brains from AD patients [58,59,60]. This evidence concerns the gene NOS2 and Alzheimer disease.