There is evidence that
cannabinoid-based medicines that are selective for different targets in the
cannabinoid signalling system (e.g. receptors, inactivation mechanism,
enzymes) might be beneficial in
basal ganglia disorders, namely
Parkinson's disease (PD) and
Huntington's disease (HD). These benefits not only include the alleviation of specific motor symptoms [e.g.
choreic movements with
cannabinoid receptor type 1 (CB(1))/transient receptor potential vanilloid type 1 agonists in HD;
bradykinesia with CB(1) antagonists and
tremor with CB(1) agonists in PD], but also the delay of
disease progression due to the neuroprotective properties demonstrated for
cannabinoids (e.g. CB(1) agonists reduce excitotoxicity; CB(2) agonists limit the toxicity of reactive microglia; and
antioxidant cannabinoids attenuate oxidative damage). In addition, extensive biochemical, anatomical, physiological and pharmacological studies have demonstrated that: (i) the different elements of the
cannabinoid system are abundant in basal ganglia structures and they are affected by these disorders; (ii) the
cannabinoid system plays a prominent role in basal ganglia function by modulating the
neurotransmitters that operate in the basal ganglia circuits, both in healthy and pathological conditions; and (iii) the activation and/or inhibition of the
cannabinoid system is associated with important motor responses that are maintained and even enhanced in conditions of malfunctioning and/or degeneration. In this article we will review the available data regarding the relationship between the
cannabinoid system and basal ganglia activity, both in healthy and pathological conditions and will also try to identify future lines of research expected to increase current knowledge about the potential therapeutic benefits of targeting this system in PD, HD and other
basal ganglia disorders.