The use of cannabinoids in Parkinson’s disease

Abstract

Parkinson's disease (PD) is a very common neurodegenerative disorder in the elderly for which there is no current cure. The neuropathological hallmark is the loss of dopaminergic cells in the substantia nigra pars compacta. Current treatments use L-DOPA and dopamine agonists to replace the lack of dopamine, however such treatments have significant limitations and side effects, thus, the need for more effective therapeutics is critical. Cannabinoids (CBs), which include 9-tetrahydrocannabinol, cannabidiol and 9-tetrahydrocannabivarin, target the endocannabinoid (ECB) system, which is highly involved in dopaminergic functions. The endocannabinoid system undergoes extensive changes in PD such as upregulation of the ECB anandamide, in addition to variations in the concentration of CB receptors. These changes can be modified and corrected using CB1 and CB2 receptor ligands and by modulating the levels of the ECB catabolic enzyme fatty acid amide hydrolase (FAAH), in order to increase endogenous anandamide (AEA) levels. Therefore, CBs may represent a valid therapeutic alternative to treat PD. CB drugs may not only treat the symptoms of the disease, but may also help slow down disease progression. Nevertheless, with regards to motor symptoms of PD such as rigidity, bradykinesia, postural instability, resting tremors and levodopa-induced dyskinesia, evidence of the therapeutic effect of CBs is somewhat inconsistent. Although only evidence in the preclinical phase, more promising results have been seen in general regarding the neuroprotective effect of CBs, as well as in relation to sleep, depression and pain.