Investigating the synergistic and modulatory effects of cannabidiol with levodopa and dietary protein in Parkinson’s disease.

Parkinson’s disease (PD) is a complex neurodegenerative disorder primarily managed with levodopa, which, despite its efficacy, is limited by long-term complications and dietary interactions. An 8-week randomized clinical trial (n = 96) was designed to assess cannabidiol (CBD) as an adjunct to levodopa, examining the efficacy of dietary protein intake. Participants were assigned to either levodopa monotherapy or levodopa plus CBD (300 mg/day) and further stratified based on dietary protein control. Symptom severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). The CBD group demonstrated a significantly greater improvement in total UPDRS scores (mean reduction: 51.2 ± 4.5) compared to the levodopa-only group (36.4 ± 3.2). Within the CBD group, patients following a protein-controlled diet showed enhanced improvement (53.6 ± 4.1) compared to those without dietary control (48.9 ± 4.8; P < 0.05). Improvements were observed across motor (tremor, rigidity, bradykinesia) and nonmotor (depression, motivation, sleep) domains. CBD was well-tolerated, with only mild, transient side effects such as drowsiness and dry mouth. These findings suggest that CBD is a safe and effective adjunctive therapy for PD, capable of enhancing both motor and nonmotor symptom control. Additionally, the study also indicated that dietary protein management can influence therapeutic outcomes, underscoring the importance of integrated pharmacological and nutritional strategies in PD management. This study recommends a large-scale study to explore underlying mechanisms.