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

Abstract

BACKGROUND AND PURPOSE Previous findings have indicated that a cannabinoid, such as Δ 9‐THCV, which has antioxidant properties and the ability to activate CB 2 receptors but to block CB 1, might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD). EXPERIMENTAL APPROACH The ability of Δ 9‐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 Δ 9‐THCV attenuated the motor inhibition caused by 6‐hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ 9‐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, CB 2 receptor–deficient mice responded to 6‐hydroxydopamine in a similar manner to wild‐type animals, and CB 2 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 CB 2 receptors. In these animals, Δ 9‐THCV also caused preservation of tyrosine hydroxylase–positive neurones. This effect probably involved CB 2 receptors as it was also elicited by the selective CB 2 receptor agonist, HU‐308, and CB 2 receptor–deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB 2 but to block CB 1 receptors, Δ 9‐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