Effects of cannabidiol on behavioral and psychological symptoms of vascular dementia: A randomized, double-blind, placebo-controlled clinical trial

Introduction: Vascular dementia (VaD) is the second leading cause of major neurocognitive disorder and is frequently associated with behavioral and psychological symptoms of dementia (BPSD), which worsen clinical outcomes and increase caregiver burden. Despite their relevance, effective pharmacological treatments for BPSD in VaD are limited. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, exhibits anxiolytic, antipsychotic, and neuroprotective properties. Objective: To evaluate the efficacy, tolerability, and safety of CBD in reducing BPSD in older adults with VaD. Methods: This randomized, double-blind, placebo-controlled trial included 30 participants with VaD and clinically significant BPSD, who received either CBD (300 mg/day) or placebo for 4 weeks. Primary outcomes were changes in the Neuropsychiatric Inventory (NPI) and the Brief Psychiatric Rating Scale (BPRS) scores. Secondary outcomes included cognitive (Mini-Mental State Examination, Informant Questionnaire on Cognitive Decline in the Elderly) and functional (Katz Index, Lawton Scale) measures, along with adverse effects (Udvalg for Kliniske Undersøgelser scale). A mixed-design repeated measures analysis of variance with post hoc Sidak tests was used. Results: CBD significantly reduced NPI scores (interaction: F (1.58, 44.31) = 3.61, p = 0.05, partial eta squared ( ηp 2 ) = 0.11) and BPRS scores (interaction: F (2.12, 59.43) = 4.02, p < 0.05, ηp 2 = 0.13) compared to placebo. No significant differences were observed in cognitive or functional outcomes. Adverse events were mild and similar between groups. Conclusion: CBD was well tolerated and effectively reduced BPSD in VaD without cognitive or functional impairment. These findings warrant further trials with larger samples, extended durations, and dose-optimization strategies to confirm its therapeutic potential. This study was registered at the Brazilian Clinical Trials Registry (ReBEC; ID: RBR-686kmpz, available at https://ensaiosclinicos.gov.br/rg/RBR-686kmpz ).