Symptom-relieving and neuroprotective effects of the phytocannabinoid Delta D9-THCV in animal models of Parkinson's disease

• Published in: British journal of pharmacology 2011-08, Vol.163 (7), p.1495-1506
• Main Authors: Garcia, C, Palomo-Garo, C, Garcia-Arencibia, M, Fernandez-Ruiz, J
• Format: Article
• Language: English
• ISSN: 1476-5381
• DOI: 10.1111/j.1476-5381.2011.01278.x

Keywords: Delta *D9-THCV; cannabinoid receptors; Parkinson's disease; 6-hydroxydopamine-lesioned rats; LPS-lesioned mice; neuroprotection BACKGROUND AND PURPOSE Previous findings have indicated that a cannabinoid, such as Delta *D9-THCV, which has antioxidant properties and the ability to activate CB2 receptors but to block CB1, might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD). EXPERIMENTAL APPROACH The ability of Delta *D9-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS). KEY RESULTS Acute administration of Delta *D9-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Delta *D9-THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB2 receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB2 receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB2 receptors. In these animals, Delta *D9-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB2 receptors as it was also elicited by the selective CB2 receptor agonist, HU-308, and CB2 receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB2 but to block CB1 receptors, Delta *D9-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7