Differential Cannabinoid Receptor Expression during Reactive Gliosis: a Possible Implication for a Nonpsychotropic Neuroprotection

Activated microglia and astrocytes produce a large number of inflammatory and neurotoxic substances in various brain pathologies, above all during neurodegenerative disorders. In the search for new neuroprotective compounds, interest has turned to marijuana derivatives, since in several in vitro, in vivo, and clinical studies, they have shown a great ability to control neuroinflammation. Despite the emerging evidence regarding pharmacological activities of cannabinoids, their effective introduction into clinical therapy still remains controversial and strongly limited by their unavoidable psychotropicity. Since the psychotropic effect of cannabinoids is generally linked to the activation of the CB(1) receptor on neurons, the aim of our review is to clarify the function of the two cannabinoid receptors on glial cells and the differential role played by them, highlighting the emerging evidence of a CB(2)-mediated control of neuroinflammation that could liberate cannabinoids from the slavery of their central side effects.