The ins and outs of endocannabinoid signaling in healthy and diseased brain

The endocannabinoid signaling system regulates neuronal activity and glial cell function. While numerous studies exist on the pharmacology and coupling of cannabinoid receptors, only recently have fundamental questions been addressed regarding endocannabinoid metabolism and physiopathological function. These lipids can be independently produced and differentially activate cannabinoid 1 and 2 receptors, a diversity that creates a unique level of control of neuronal activity and glial cell functions. This review outlines our current understanding of this diversity, focusing on the stimuli that control endocannabinoid production in the brain under healthy and pathological conditions. By increasing this understanding, new pharmacological targets are likely be identified, some of which might be valuable for the treatment of neurological disease.