Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection

Abstract

Parkinson’s disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure. Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD. The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems. As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD. Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons. Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD. Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.

Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity

“…Interestingly, cannabinoid receptor agonist WIN-55,212-2 is shown to have neuroprotective effects for Parkinson's disease, suppressing excitotoxicity, glial activation and oxidative injury of dopaminergic neurons 60 . It is possible that GPR55 may exert its effects in dopaminergic neurons to regulate physical activity.…”

The potential utility of some legal highs in CNS disorders

“…7 | P a g e 11-hydroxytetrahydrocannabinol) have been found to be neuroprotective in preclinical models of Parkinson's disease (reviewed by More and Choi, 2015) and may also be useful in Alzheimer's disease (Ramirez et al, 2005) but this is not always the case (Chen et al, 2010). Also in the current issue, (Wilkes, 2008) and diethylpropion, used for weight loss (Cercato et al, 2009).…”

“…In the current issue, Mursaleen and Stamford (2015) review the utility of cannabinoids in Parkinson's disease. The evidence that they present clearly suggests that cannabinoids may be of some use, not only in treating the symptoms of Parkinson's disease, but also in reducing L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (More and Choi, 2015). Sierradzan et al, (2001) examined the synthetic cannabinoid nabilone in Parkinson's disease and found reduced L-DOPA induced dyskinesias.…”

Endocannabinoid Systetm: Neuropharmacological Implications

“…Thus development of safe, effective cannabis-based medicines targeting different mechanisms may have a significant impact in PD therapy [56].…”