Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

Abstract

Movement disorders such as Parkinson's disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.

Keywords: Huntington's disease; Parkinson's disease; cannabidiol; cannabinoids; dystonic disorders; movement disorders.

Figure 1

CBD's mechanisms of action. CBD acts as agonist of the receptors TRPV1, PPARγ, and 5-HT_1A, and as antagonist of the receptor GPR55. CBD is an inverse agonist of the receptors GPR3, GPR6, and GPR12. Moreover, CBD antagonizes the action of CB₁ and CB₂ receptors agonists, and is suggested to act as an inverse agonist and a negative allosteric modulator of these receptors. CBD also inhibits FAAH, which results in increased anandamide levels. Anandamide activates CB₁, CB₂, and TRPV1 receptors. By acting on mitochondria, CBD increases the activity of mitochondrial complexes. In addition, CBD displays antioxidant and anti-inflammatory effects—that are partially mediated by CBD's actions on TRPV1, mitochondria and PPARγ. 5-HT_1A, serotonin receptor 1A; CB₁, cannabinoid receptor type 1; CB₂, cannabinoid receptor type 2; FAAH, fatty acid amide hydrolase; GPR3, G-protein-coupled receptor 3; GPR6, G-protein-coupled receptor 6; GPR12, G-protein-coupled receptor 12; GPR55, G-protein-coupled receptor 55; PPARγ, peroxisome proliferator-activated receptor gamma; ROS, reactive oxygen species; TRPV1, transient receptor potential vanilloid type 1.