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