{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:45:35Z","timestamp":1790729135044,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T00:00:00Z","timestamp":1308009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We studied whether combinations of botanical extracts enriched in either \u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (\u0394<jats:sup>9<\/jats:sup>\u2010THC) or cannabidiol (CBD), which are the main constituents of the cannabis\u2010based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3\u2010nitropropionate (3NP) that were given combinations of \u0394<jats:sup>9<\/jats:sup>\u2010THC\u2010 and CBD\u2010enriched botanical extracts. The issue was also studied in malonate\u2010lesioned rats. The administration of \u0394<jats:sup>9<\/jats:sup>\u2010THC\u2010 and CBD\u2010enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP\u2010induced GABA deficiency, loss of Nissl\u2010stained neurons, down\u2010regulation of CB<jats:sub>1<\/jats:sub> receptor and IGF\u20101 expression, and up\u2010regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase\u20101 expression. Similar responses were generally found with other combinations of \u0394<jats:sup>9<\/jats:sup>\u2010THC\u2010 and CBD\u2010enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB<jats:sub>1<\/jats:sub> and CB<jats:sub>2<\/jats:sub> receptor\u2010independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP\u2010intoxicated rats by the 1:1 combination of \u0394<jats:sup>9<\/jats:sup>\u2010THC and CBD. Finally, this combination also reversed the up\u2010regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate\u2010lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis\u2010based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22682","type":"journal-article","created":{"date-parts":[[2011,6,15]],"date-time":"2011-06-15T09:22:10Z","timestamp":1308129730000},"page":"1509-1518","source":"Crossref","is-referenced-by-count":92,"title":["Neuroprotective effects of phytocannabinoid\u2010based medicines in experimental models of Huntington's disease"],"prefix":"10.1002","volume":"89","author":[{"given":"Onintza","family":"Sagredo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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