Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer’s Disease

Objective: This meta-analysis investigated the efficacy of cannabinoids on agitation and aggression in patients with Alzheimer's disease (AD). Data Sources: Electronic records up to August 2018 were searched from MEDLINE, EMBASE, and PsycINFO. Search terms included Alzheimer's disease, agitation, aggression, and cannabinoids. Study Selection: Double-blind, placebo-controlled studies investigating the effect of cannabinoids on agitation in patients with AD were included. Of the 1,336 records returned, 123 were reviewed and 6 (N = 251 participants) were included. Data Extraction: Data on demographics, study setting, trial length, intervention, outcomes, and dropouts were extracted. Results: There was no effect of cannabinoids as a group on agitation (standard mean difference: -0.69, P = .10), though there was significant heterogeneity (chi(2)(6) = 43.53, P < .00001, I(2) = 86%). There was a trend for greater difference in agitation with synthetic cannabinoids over tetrahydrocannabinol (chi(2)(1) = 3.05, P = .08). Cannabinoids had a larger effect on agitation with greater cognitive impairment (B = 0.27, t(6) = 2.93, P = .03). Cannabinoids did not change overall neuropsychiatric symptoms or body mass index (BMI). However, there was a significant difference in patients with a lower BMI compared to patients with a higher BMI (chi(2)(1) = 4.63, P = .03). Sedation was significantly greater with cannabinoids compared to placebo (risk ratio = 1.73, P = .04), but there were no differences in the occurrence of adverse events or dropouts due to an adverse event between treatment groups. Conclusions: The efficacy of cannabinoids on agitation and aggression in patients with AD remains inconclusive, though there may be a signal for a potential benefit of synthetic cannabinoids. Safety should be closely monitored as cannabinoid treatment was associated with increased sedation.