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00925njm 22002777a 4500 dc Fernández Ruiz, José Javier author Moreno Martet, Miguel author Rodríguez Cueto, Carmen Aurora author Palomo Garo, Cristina author Gómez Cañas, María author Valdeolivas, Sara author Guaza, Carmen author Romero, Julián author Guzmán Pastor, Manuel author Mechoulam, Raphael author Ramos Atance, José Antonio author 2011 Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9‐tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB1 and CB2 receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB2 receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB2 receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up‐regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB2 receptor up‐regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB2 receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB2receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation. Fernández-Ruiz J, Moreno-Martet M, Rodríguez-Cueto C, Palomo-Garo C, Gómez-Cañas M, Valdeolivas S, Guaza C, Romero J, Guzmán M, Mechoulam R, Ramos JA. Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol. 2011 Aug;163(7):1365-78. doi: 10.1111/j.1476-5381.2011.01365.x. PMID: 21545415; PMCID: PMC3165947. 0007-1188 10.1111/j.1476-5381.2011.01365.x https://hdl.handle.net/20.500.14352/93221 https://doi.org/10.1111/j.1476-5381.2011.01365.x https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01365.x Prospects for cannabinoid therapies in basal ganglia disorders