Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson's disease

BACKGROUND AND PURPOSE Previous findings have indicated that a cannabinoid, such as Δ9‐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 Δ9‐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 Δ9‐THCV attenuated the motor inhibition caused by 6‐hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ9‐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, Δ9‐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, Δ9‐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