 The contribution of MAGL to total brain 2-AG hydrolysis activity has been estimated to be ~85% (ABHD6 and ABHD12 are responsible for ~4% and ~9%, respectively, of the remainder), and this "in vitro" estimate has been confirmed "in vivo" by the selective MAGL inhibitor JZL184.Chronic inactivation of MAGL results in massive (>10-fold) elevations of brain 2-AG in mice, along with marked compensatory downregulation of CB1 receptors in selective brain areas.MAGL enzyme inhibitors (URB602, URB754, JZL184) produce cannabinoid behavioral effects in mice.