Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis.

Tudella G.; Klostermann A.; Menegucci G.; Fernandes J.; Pacheco J. · Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026

**Background & Methods** This systematic review and meta-analysis synthesized randomized controlled trials evaluating cannabinoid-based therapies for behavioral and cognitive symptoms in Alzheimer's disease and dementia. Nine trials comprising 334 participants were included, with primary outcomes measured by the Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and secondary outcomes assessing cognition via Mini-Mental State Examination (MMSE). **Key Findings** - Cannabinoids demonstrated no significant improvement in agitation measured by CMAI (SMD -0.58, 95% CI -1.71 to 0.55) or NPI-NH total scores (SMD -0.02, 95% CI -1.00 to 0.96), with Bayesian posterior estimates supporting absence of effect. - No cognitive benefit was observed on MMSE scores (SMD 0.86, 95% CI -16.33 to 18.06), with substantial heterogeneity noted across trials (I² = 96%). - Secondary analysis of NPI-NH agitation subscale similarly showed no significant cannabinoid effect (SMD -0.44, 95% CI -1.45 to 0.57), suggesting lack of benefit across multiple behavioral outcome measures. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Overall adverse events occurred at rates similar to placebo. However, somnolence was significantly more frequent in cannabinoid-treated groups compared to control (Risk Ratio 2.03, 95% CI 1.29-3.20), representing a notable safety concern that should be considered in clinical decision-making. **Evidence Quality** Certainty of evidence was rated as moderate for behavioral outcomes and low for cognitive outcomes using GRADE methodology. Significant heterogeneity was present across trials (I² values 48-96%), which persisted even after leave-one-out sensitivity analyses, suggesting variability in study populations, interventions, or methodological quality. Risk of bias was evaluated using the RoB 2 tool. The modest sample size (334 participants across 9 trials) and variability in outcome measurement and cannabinoid formulations limit generalizability. These limitations, combined with null findings across primary and secondary outcomes, indicate that current evidence does not support cannabinoid use for managing behavioral and cognitive symptoms in dementia.

More recent cannabis research