The endocannabinoid system includes two G-protein coupled cannabinoid receptors (CB1 and CB2), their endogenous lipid ligands (endocannabinoids), and the enzymes and transporters that help regulate cannabinergic tone ( 1 ). Endocannabinoid signaling is ubiquitous in mammals, being particularly critical in brain , where it modulates neurotransmitter release and exhibits neuroprotective effects ( 2, 3 ). Although the fi rst two endocannabinoids identifi ed, N -arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (AG), have been extensively characterized, the (patho)physiological impact of endocannabinoid signaling has prompted the search for additional endocannabinoids and their related metabolites/ biosynthetic precursors, creating an evolving network of chemical species collectively termed the endocannabinoid metabolome, few of which have been functionally annotated ( 1,(3)(4)(5)(6)(7)(8)(9). Although the translational and diagnostic aspects of endocannabinoid signaling are well appreciated ( 10, 11 ), factors that infl uence and regulate the endocannabinoid metabolome profi le among various tissues and compartments remains incompletely described and understood ( 1, 10 ), as are the metabolome's relationship to lipid pathways outside of the endocannabinoid signaling system ( 3, 9 ).
Abstract