The Role of Cannabidiol (CBD) in Parkinson's Disease Treatment - Mechanisms, Therapeutic Potential, and Implications for Motor and Non-Motor Symptoms

This preprint presents a comprehensive review of the therapeutic potential of Cannabidiol for treating Parkinson's disease, as detailed in the document CBD_Parkinsons_Treatment_Report (1).pdf. Parkinson's disease is a progressive neurodegenerative condition primarily caused by the loss of dopaminergic neurons, resulting in debilitating motor and non-motor symptoms. Standard treatments like Levodopa often lose efficacy over time and cause severe side effects such as Levodopa-induced dyskinesia. Unlike conventional treatments, Cannabidiol is a non-intoxicating compound with an excellent safety profile. The review surveys evidence regarding the impact of Cannabidiol on various symptoms and its neurodegenerative pathway mechanisms. Evidence suggests Cannabidiol modestly improves rigidity and bradykinesia, and in preclinical models, it prevents dopamine depletion in the striatum. It also significantly reduces abnormal involuntary movements associated with Levodopa-induced dyskinesia without diminishing the primary motor benefits of Levodopa. For non-motor symptoms, oral Cannabidiol significantly reduces psychotic symptoms without worsening motor function. It also causes a prompt reduction in REM sleep behavior disorder events and improves overall well-being and quality of life scores in patients. The underlying mechanisms of these therapeutic actions are multifaceted. Cannabidiol acts as a potent antioxidant capable of neutralizing reactive oxygen species and restoring mitochondrial membrane potential. It exhibits robust anti-inflammatory properties by downregulating pro-inflammatory cytokines and preventing microglial activation in the striatum and substantia nigra. Additionally, Cannabidiol modulates the endocannabinoid system by acting as a negative allosteric modulator at CB1 receptors, a partial agonist or inverse agonist at CB2 receptors, and an antagonist at GPR55 receptors. Finally, it acts as an agonist at the serotonin receptor, which is critical to its anxiolytic and anti-dyskinetic effects. Keywords: Cannabidiol, neuroprotection, dyskinesia, psychosis, endocannabinoid