Endocannabinoid signaling in the brain: biosynthetic mechanisms in the limelight

Studies of the endocannabinoid system in the CNS have been mostly focused on endocannabinoid receptors and inactivating mechanisms. Until recently, very little was known about the role of biosynthetic enzymes in endocannabinoid signaling. New data from the recent development of pharmacological and genetic tools for the study of these enzymes point to their fundamental role in determining where and when endocannabinoids function, and raise the possibility of new intriguing and previously unsuspected concepts in the general strategy of endocannabinoid signaling. However, even with these new tools, the cross-talk between anandamide and 2-arachidonoylglycerol biosynthesis makes it difficult to dissect one from the other, and data will need to be interpreted with this in mind.