A new study published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry found that cannabidiol (CBD), along with its fluorinated derivative PECS-101, can significantly reduce L-DOPA-induced dyskinesia (LID) in an animal model of Parkinson’s disease—without diminishing the motor benefits of L-DOPA.
“Despite the widespread use of L-3,4-dihydroxyphenylalanine (L-DOPA) as the gold standard for dopamine (DA) replacement in Parkinson’s Disease (PD), its prolonged administration frequently leads to L-DOPA-induced dyskinesia (LID), a significant therapeutic challenge”, states the study’s abstract. “Modulating the endocannabinoid system has emerged as a promising approach for managing LID.
With that in mind, this study “explored whether cannabidiol (CBD), a non-psychoactive compound of Cannabis sativa, and PECS-101, a fluorinated derivative of CBD, could mitigate the onset and progression of LID.
For the study, researchers from the University of São Paulo administered L-DOPA to rats with chemically induced Parkinson-like symptoms over a three-week period to simulate the development of severe abnormal involuntary movements (AIMs). CBD and PECS-101 were introduced during the final two weeks and were shown to markedly suppress these movements. The reduction in dyskinesia was linked to decreased expression of striatal markers Fos-B and phospho-ERK, and occurred independently of lesion severity.
The study also identified the key roles of the CB1 and PPARγ receptors in mediating CBD’s effects, as blocking either receptor reversed the benefits. Meanwhile, blocking TRPV-1 enhanced CBD’s efficacy, especially when combined with an inhibitor of neuronal nitric oxide synthase. Though CBD did not alter dopamine levels in the striatum, it significantly increased levels of the endocannabinoids anandamide and 2-AG and was associated with reduced neuroinflammation.
“These findings suggest that CBD alleviates LID by interacting with the nitrergic neurotransmission and TRPV-1, CB1, and PPARγ receptors”, concludes researchers.
For the full study, click here.
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