Objective: To assess the safety, tolerance, and effectiveness of an oil extract of Cannabis sativa L. on pain and other non-motor symptoms (NMS) in people with Parkinson’s disease (PD).

Background: Pain is a frequent in PD, affecting about 20% of patients at diagnosis and up to 80% over the disease course, with a substantial impact on quality of life. Other NMS are also common and are often less responsive to therapy than motor. There is a lack of treatments for pain and NMM in people with PD.

Method: This was a phase II, randomized, double-blind, placebo-controlled trial evaluating an oral formulation of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), conducted from November 2022 to July 2025 at the Hospital das Clínicas, University of São Paulo. PD patients with pain complaints received a Cannabis extract (CBD 96mg/mL;THC 2.1mg/mL) for 9 weeks. The primary outcome was assessed by between-group differences in PD–Pain Classification System scores (PCS) at the final visit. Secondary outcomes included the Brief Pain Inventory (BPI) severity and interference scores, the proportion of participants achieving ≥ 30% reduction in pain intensity, MDS-Non-motor Symptoms Scale, the Scale for Outcomes in PD-Autonomic Dysfunction, the Hospital Anxiety and Depression Scale, the Montreal Cognitive Assessment, PD Questionnaire (PDQ-8), and the Patient Global Impression of Change. Motor symptoms were assessed with part III MDS-UPDRS, the New Freezing of Gait Questionnaire, and the Timed Up-and-Go scale.

Results: A total of 101 participants were randomized (50 were assigned to the CBD/THC group and 51 to the placebo group) and 87 completed the study. The median age was 63 years (IQR:54-70), 34% were female, and the median PD duration was seven years (IQR:1-32). There was no significant difference in PD-PCS scores between the CBD/THC and placebo groups (p=0.757). Moreover, there were no differences in the BPI (p =0.776), non-motor, and motor scales. Both groups showed improvements in pain from baseline to the final visit. There were no differences in adverse events, except for irritability in the CBD/THC group (p = 0.005).

Conclusion: In this study, an oral Cannabis oil formulation did not improve pain or other NMS in people with PD. Studies with different formulations and dosing should further explore the relevance of Cannabis oil for PD non-motor symptoms.

Flow of study participants.

Baseline demographic and clinical characteristics

Primary and secondary outcomes

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