TY - JOUR T1 - Cannabidiol and other cannabinoids reduce microglial activation <em>in vitro</em> and <em>in vivo</em>: relevance to Alzheimers′ disease JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.111.071290 SP - mol.111.071290 AU - Ana Maria Martin-Moreno AU - David Reigada AU - Belen G. Ramirez AU - Raphael Mechoulam AU - Nadia Innamorato AU - Antonio Cuadrado AU - Maria L. de Ceballos Y1 - 2011/02/24 UR - http://molpharm.aspetjournals.org/content/early/2011/02/24/mol.111.071290.abstract N2 - Microglial activation is an invariant feature of Alzheimer′s disease (AD). Interestingly cannabinoids are neuroprotective by preventing β-amyloid (Aβ) induced microglial activation both in vitro and in vivo. On the other hand, the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in different paradigms. In the present study we compared the effects of CBD with those of other cannabinoids on microglial cell functions in vitro and on learning behaviour and cytokine expression following Aβ intraventricular administration to mice. CBD, WIN 55,212-2 (WIN), a mixed CB1/CB2 agonist, and JWH-133 (JWH), a CB2 selective agonist, concentration-dependently decreased ATP-induced (400 [micro]M) increase in intracellular calcium ([Ca2+]i) in cultured N13 microglial cells and in rat primary microglia. In contrast HU-308 (HU), another CB2 agonist, was without effect. Cannabinoid and adenosine A2A receptors may be involved in the CBD action. CBD and WIN-promoted primary microglia migration was blocked by CB1 and/or CB2 antagonists. JWH and HU-induced migration was blocked by a CB2 antagonist only. All the cannabinoids decreased LPS-induced nitrite generation, which was insensitive to cannabinoid antagonism. Finally both CBD and WIN, following subchronic administration for three weeks, were able to prevent learning of a spatial navigation task and cytokine gene expression in β-amyloid injected mice. In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity it may represent a novel therapeutic approach for this neurologic disease. ER -