Effects of Broad Spectrum Cannabidiol Oil on Behavioral Disturbances in Patients with Dementia: A Randomized Clinical Trial

Abstract Background: Almost 90% of patients with dementia suffer from some type of neurobehavioral symptom and there are no approved medications for these symptoms. We aimed to evaluate the safety and efficacy of Avidekel compared with a placebo for the reduction of behavioral disturbances among patients with dementia.Methods: In this randomized, double-blind, placebo-controlled trial conducted in a medical center in northern Israel, male and female patients, aged at least 60, with a diagnosis of major neurocognitive disorder and associated behavioral disturbances were randomized 2:1 to receive either Avidekel oil (30% cannabidiol and 1% tetrahydrocannabinol: 295 mg and 12.5 mg per ml respectively; n=40), or a placebo oil (n=20) three times a day for 16 weeks. The primary outcome was a decrease, as compared to baseline, of four or more points on the Cohen-Mansfield Agitation Inventory score by week 16. Secondary outcomes included: mean change in the Cohen-Mansfield Agitation Inventory, the time necessary to achieve a 4-point reduction in Cohen-Mansfield Agitation Inventory, mean change in Neuropsychiatric Inventory agitation/aggression sub-score.Results: Among 60 randomized patients (mean age, 79.4 years; 36 women [60.0%]), 52 (86.7%) completed the trial (all eight patients who discontinued treatment were from the investigational group). There was a statistically significant difference in the proportion of subjects who had a Cohen-Mansfield Agitation Inventory score reduction of ≥4 points at week 16: 24/40 (60.0%) and 6/20 (30.0%) for investigational and control groups, respectively (P<.05). The ANOVA repeated measures analysis demonstrated significantly better improvement in the investigational group compared to the control group in weeks 14 and 16 (P<.05). The Neuropsychiatric Inventory results demonstrated a significant reduction (>29%) in agitation/aggression (P<.05). There were no significant differences in the occurrence of adverse events between the two groups. Conclusions: In this randomized controlled trial, Avidekel oil significantly reduced agitation over placebo in patients suffering from behavioral disorders related to dementia, with minimal side-effects. Further research is required involving various sub-types of dementia and a larger sample size.Trial Registration: ClinicalTrials.gov Identifier: NCT03328676. Registered on November 1, 2017.