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.