Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial

Vered Hermush, Liora Ore, Noa Stern, Nisim Mizrahi, Malki Fried, Marina Krivoshey, Ella Staghon, Violeta E Lederman, Lihi Bar-Lev Schleider, Vered Hermush, Liora Ore, Noa Stern, Nisim Mizrahi, Malki Fried, Marina Krivoshey, Ella Staghon, Violeta E Lederman, Lihi Bar-Lev Schleider

Abstract

Background: Almost 90% of patients with dementia suffer from some type of neurobehavioral symptom, and there are no approved medications to address these symptoms.

Objective: To evaluate the safety and efficacy of the medical cannabis oil "Avidekel" for the reduction of behavioral disturbances among patients with dementia.

Materials and methods: In this randomized, double-blind, single-cite, placebo-controlled trial conducted in Israel (ClinicalTrials.gov: NCT03328676), patients aged at least 60, with a diagnosis of major neurocognitive disorder and associated behavioral disturbances were randomized 2:1 to receive either "Avidekel," a broad-spectrum cannabis 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.

Results: From 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 (χ2 = 4.80, P = 0.03). There was a statistically significant difference in the proportion of subjects who had a Cohen-Mansfield Agitation Inventory score reduction of ≥ 8 points at week 16: 20/40 (50%) and 3/20 (15%), respectively (χ2 = 6.42, P = 0.011). The ANOVA repeated measures analysis demonstrated significantly more improvement in the investigational group compared to the control group at weeks 14 and 16 (F = 3.18, P = 0.02). Treatment was mostly safe, with no significant differences in the occurrence of adverse events between the two groups.

Conclusion: In this randomized controlled trial, 'Avidekel' oil significantly reduced agitation over placebo in patients suffering from behavioral disturbances related to dementia, with non-serious side-effects. Further research is required with a larger sample size.

Keywords: agitation; behavioral disturbances; cannabidiol; dementia; medical cannabis; neuropsychiatric symptoms; randomized controlled trial (RCT).

Conflict of interest statement

LB-L and VL report employment at Tikun-Olam Cannbit Pharmaceuticals Ltd., with stock options in the company. LB-L reports consulting role with TO Pharmaceuticals LLC. As a consultant of the company, LB-L was registered as an inventor on a patent on the investigational product for behavioral disturbance in patients with dementia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Hermush, Ore, Stern, Mizrahi, Fried, Krivoshey, Staghon, Lederman and Bar-Lev Schleider.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram.
FIGURE 2
FIGURE 2
The Cohen-Mansfield Agitation Inventory score reduction over time between groups. Panels (A,B) present mean CMAI scores in the two groups, throughout the trial visits both in intention-to-treat analysis of all randomized patients that initiated treatment (n = 60), and per protocol analysis of patients who completed the trial according to protocol (n = 52). (A) Intention-to-treat analysis. (B) Per-protocol analysis.

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