CB1 cannabinoid receptor signalling in Parkinson's disease

Signalling at CB1, cannabinoid receptors plays a key role in the control of movement in health and disease. In recent years, an increased understanding of the physiological role of transmission at CB1, receptors throughout the basal ganglia circuitry has led to the identification of novel therapeutic approaches to both the symptoms of Parkinson's disease and the side effects of current anti-parkinsonian therapies, especially L-3,L-4 dihydroxyphenylalamine (levodopa)-induced dyskinesia. Thus, because activation of basal ganglia CB1 receptors can modulate neurotransmission and contribute to synaptic plasticity in a manner similar to that described in other brain regions, it also appears that endocannabinoids might modulate cell-cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types. Recent studies in animal models and in the clinic suggest that CB1 receptor antagonists could prove useful in the treatment of parkinsonian symptoms and levodopa-induced dyskinesia, whereas CB1 receptor agonists could have value in reducing levodopa-induced dyskinesia.