Endocannabinoid metabolism in neurodegenerative diseases.

Endocannabinoids are endogenous lipid mediators contributing to a variety of physiological, pharmacological, and pathological processes primarily through acting on cannabinoid receptors (CB1R and CB2R), which are targets of Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in marijuana.[1] Although N-arachidonoyl ethanolamide is the first identified endocannabinoid, 2-arachidonoylglycerol (2-AG), the second identified endocannabinoid, is the most abundant ligand produced in our body and a full agonist for CB1R and CB2R.[2] It has been well recognized that 2-AG is a retrograde messenger modulating synaptic transmission and plasticity at both inhibitory GABAergic and excitatory glutamatergic synapses in the brain.[2-4] In particular, augmentation of 2-AG signaling by inhibition of its metabolism has been attracted attention recently due to its profound antiinflammatory and neuroprotective properties.[4,5]