Recent peer-reviewed research reveals complex mechanisms of cannabinoid action in Parkinson’s disease (PD). The endocannabinoid system (ECS) plays a crucial role in modulating basal ganglia function and PD progression through multiple pathways. Receptor Mechanisms The ECS primarily operates through CB1 and CB2 receptors, with CB1 receptors being particularly abundant in the basal ganglia, cortex, cerebellum, and hippocampus[1][3]. The main endocannabinoids involved are: – 2-AG (full agonist): Activates both CB1 and CB2 receptors, with levels 170-fold higher than AEA in the brain[3]– Anandamide (AEA, partial agonist): Preferentially activates CB1 receptors[3] Neurotransmitter Interactions Endocannabinoids regulate basal ganglia circuits through bidirectional communication with multiple neurotransmitter systems[2]. This includes: – Dopaminergic signaling modulation– Glutamatergic transmission regulation– GABAergic system interaction Neuroprotective Mechanisms The ECS demonstrates neuroprotective effects through: – Reduction of neuroinflammation– Suppression of excitotoxicity– Mitigation of oxidative stress– Regulation of glial activation[2] Clinical Implications…