To provide an updated evaluation examining the therapeutic effect of cannabinoids (CBD) on Parkinson's disease (PD) patients.

Although levodopa has been a cornerstone of PD treatment for years, it provides only symptomatic relief, and its benefits diminish over time. As the disease progresses and the dosage increases, patients develop motor fluctuations and dyskinesia, impairing their quality of life. All of this highlights the need for alternative treatments. CBD have emerged as potential therapeutic candidates due to their neuroprotective and anti-inflammatory effects; however, the evidence remains inconclusive.

A literature search was conducted through PubMed, Scopus, and Web of Science to identify RCTs evaluating CBD in PD. Quality assessment was done using the RoB-2 tool. Random-effects meta-analyses were performed in R, reporting mean differences (MD) or standardized mean differences (SMD; Hedges g) with 95% confidence intervals (CIs). A sensitivity analysis was performed to assess the robustness of the results. In crossover trials, effect sizes and standard errors (SE) were extrapolated from the reported CIs, taking into account the paired design.

Eleven RCTs were identified, six of which were eligible for meta-analysis. CBD did not significantly improve PD severity (SMD= 0.16, 95%CI [-0.13 to 0.44], p=0.27), motor examination (SMD= -0.08, 95%CI [-0.35 to 0.20], p=0.57), motor activities of daily living (SMD= -0.08, 95%CI [-0.49 to 0.33], p=0.71), non-motor symptoms (SMD= -0.03, 95%CI [-0.72 to 0.67], p=0.94),  quality of life (MD= 1.16, 95%CI [-3.22 to 5.55], p= 0.60), depression (MD= 0.66, 95% CI[-0.37 to 1.69], p=0.21), anxiety (MD= 0.24, 95%CI [-0.76 to 1.24], p=0.64). Most analyses showed no heterogeneity, except for non-motor symptoms (I²=64.3%, p=0.06), where excluding Peball et al resolved the heterogeneity (I²=0%, p=0.94).

Current evidence is still insufficient to support a significant therapeutic effect of CBD on PD patients. Clarification of its therapeutic role requires larger, more rigorous trials with standardized protocols.