Basal ganglial circuitry in Parkinson’s disease (PD) and tentative cannabinoid targets to improve motor disability in PD. Progressive loss of dopaminergic innervation in PD causes overactivity of the indirect (inhibitory) pathway, resulting in excess glutamatergic drive to the GPi and SNpr and diminished activity of the inhibitory GABAergic direct pathway, further disinhibiting the activity of the GPi and SNpr. As output nuclei (GPi and SNpr) use the inhibitory neurotransmitter GABA, this amplified basal ganglia output leads to extreme inhibition of the motor thalamus which acts as a “brake” on motor activity; thus, resulting in the onset of parkinsonian syndrome. The neural circuitry above depicts various possible cannabinoid- based targets (CB1, CB2, and TRPV1 receptors) that can be used to mitigate the symptoms observed in PD. Abbreviations: CB1, cannabinoid receptor 1; TRPV1, transient receptor potential vanilloid 1; GPe, external segment of the globus pallidus; GPi, internal segment of the globus pallidus; SNpc, substantia nigra pars compacta; SNpr, substantia nigra pars reticulata; STN, subthalamic nucleus; GABA, gamma-aminobutyric acid.