Neuroinflammation and the glial endocannabinoid system

Abstract

The remarkable density and wide distribution of cannabinoid CB1 receptors in the central nervous system served to explain many of the well-known pharmacological effects of natural, synthetic and endogenous cannabinoids. This receptor type is one of the most abundant cerebral receptors so far described. Its presynaptic location in neurons allows its participation in a myriad of cerebral functions, such as those controlling motor activity or memory and to mediate cannabinoid-induced neuroprotection. At the same time, the psychoactive effects derived from CB1 activation limited the development of novel therapeutic approaches on the use of cannabinoids. However, recent data have raised the possible interest of the endocannabinoid system in neuroinflammation. These new perspectives can be summarized mostly at two levels: (1) the participation of other components of the endocannabinoid system, mainly CB2 receptors and fatty acid amide hydrolase (FAAH), in neuroinflammatory processes; and (2) the predominance of the glial endocannabinoid system over the neuronal endocannabinoid system under pathological conditions. We now know that dramatic changes take place in the endocannabinoid system in the human brain, suggesting its possible involvement in several prevalent diseases, such as Alzheimer's disease, multiple sclerosis or viral encephalitis. This is the subject of the present review.