The Cannabigerol Derivative VCE-003.2 Exerts Therapeutic Effects in 6-Hydroxydopamine-Lesioned Mice: Comparison with The Classic Dopaminergic Replacement Therapy

Abstract

(1) Background: A cannabigerol aminoquinone derivative, so-called VCE-003.2, has been found to behave as a neuroprotective agent (administered both i.p. and orally) in different experimental models of Parkinson’s disease (PD) in mice. These effects were exerted through mechanisms that involved the activation of a regulatory site within the peroxisome proliferator-activated receptor-γ (PPAR-γ). (2) Methods: We are now interested in comparing such neuroprotective potential of VCE-003.2, orally administered, with the effect of the classic dopaminergic replacement therapy with L-DOPA/benserazide in similar conditions, using 6-hydroxydopamine-lesioned mice. (3) Results: The oral administration of VCE-003.2 during 14 days at the dose of 20 mg/kg improved, as expected, the neurological status (measured in motor tests) in these mice. This correlated with a preservation of TH-labelled neurons in the substantia nigra. By contrast, the treatment with L-DOPA/benserazide (during 7 days at 2 mg/kg) was significantly less active in these experimental conditions, in concordance with their profile as a mere symptom-alleviating agent. (4) Conclusions: Our results confirmed again the therapeutic profile of VCE-003.2 in experimental PD and revealed a different and more relevant effect, as a disease modifier, compared to the classic symptom-alleviating L-DOPA treatment. This reinforces the interest in VCE-003.2 for a future clinical development in this disease.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…However, other cannabinoids have not been extensively studied. Future research could focus on clinical trials to investigate the therapeutic potential of these lesser-known cannabinoids and their derivatives, which have proven in vitro or in vivo biological activity, such as the following: THCV-antiepileptic activity [347], potential against Parkinson's disease [348,349], antipsychotic effects [350], CBG-anticonvulsant activity [351], counteract neuroinflammation [352], neuroprotective in Huntington's disease [202], in multiple sclerosis [353], CBG derivatives-anti-inflammatory in multiple sclerosis [354], in amyotrophic lateral sclerosis [355], neuroprotective potential in Huntington's disease [356], in Parkinson's disease [357][358][359], CBC-promotes neural stem/progenitor cells viability [360], induces neuronal differentiation in NSC-34 Cells [361], antinociceptive activity [362], anti-inflammatory [363], CBN-neuroprotective activity [167], antiseizure potential [364].…”