Efficacy of Cannabinoids for Agitation, Aggression in Alzheimer Disease Inconclusive

Cannabis leaves in laboratory for research
The efficacy of cannabinoids on agitation and aggression in patients with Alzheimer disease remains inconclusive, but there might be a benefit with synthetic cannabinoids.

Little evidence for the efficacy of cannabinoids on agitation in Alzheimer disease (AD) was found in a meta-analysis published in the Journal of Clinical Psychiatry, but the results were not conclusive.

Neuropsychiatric symptoms occur in up to 90% of patients with AD and increase in prevalence and severity as the disease progresses. Agitation occurs in up to 50% of patients with moderate to severe AD and is one of the most challenging neuropsychiatric symptoms to manage. Medications currently used to treat agitation in patients with AD have limited efficacy and are often associated with harmful adverse events. The endocannabinoid pathway has been implicated in AD, suggesting that cannabinoids might have therapeutic potential for the management of the disease.

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Myuri Ruthirakuhan, MSc, of the Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada, and the Department of Pharmacology and Toxicology, University of Toronto, and colleagues, searched electronic records up to August 2018 from MEDLINE, EMBASE, and PsycINFO using the search terms Alzheimer’s disease, agitation, aggression, and cannabinoids. They included 6 double-blind placebo-controlled studies investigating the effect of cannabinoids on agitation in a total of 251 patients with AD.

The investigators found no effect of cannabinoids as a group on agitation, although there was significant variation (X26=43.53, P <.00001, I2=86%). They found a trend for greater difference in agitation with synthetic cannabinoids compared with tetrahydrocannabinol (X21=3.05, P =.08). They also found a larger effect on agitation in patients who had greater cognitive impairment (B=0.27, t6=2.93, P =.03).

The investigators found no change with cannabinoids in overall neuropsychiatric symptoms or body mass index. Compared with patients receiving placebo, patients receiving cannabinoids had significantly greater sedation (risk ratio, 1.73; P =.04). No other differences in adverse events came to light.

The analysis is limited by the small number of studies and participants included and the large variability in these studies, which resulted in wide 95% CIs.

Researchers noted that more rigorous studies are needed, as treatment of agitation and aggression in AD is important and cannabinoids still represent a potentially useful class of agents.


Ruthirakuhan M, Lanctôt KL, Vieira D, Herrmann N. Natural and synthetic cannabinoids for agitation and aggression in Alzheimer’s disease. J Clin Psychiatry. 2019;80(2).