Cannabis Resin Extract in Parkinson’s Disease: Behavioral, Neurochemical, and Histological Evaluation

Cannabis sativa (Family Cannabaceae, L.) has been used in China and India for thousands of years as a medicine. The main active constituents of cannabis are Δ 9 -tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD). Currently, THC and CBD are being carefully used in conditions, such as multiple sclerosis, cancer pain, and chemotherapy associated emesis. The cannabinoid 1 receptor (CB1R) is considered responsible for most THC effects involving sedation, analgesia, hypothermia, catalepsy, and euphoria . CB1Rs are abundantly distributed in the basal ganglia , where they are co-localized with both dopamine (D)1 and 2 receptors on striatonigral dynorphin/substance P and striatopallidal enkephalinergic neuron. In striatum, CB1R is highly expressed in γ-aminobutyric acid (GABA)ergic and glutamatergic presynaptic terminals, where it mediates retrograde endocannabinoid signalling . The inhibition of GABA and glutamate systems in basal ganglia, in turn suppresses D1-mediated effects to exert an anti-dyskinetic action. Additionally, the basal ganglia expresses the cannabinoid 2 receptor (CB2R), particularly in glial cells entailing a role for CB2R-agonists in reducing microglia toxic effects and inflammatory reactions.