Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is frequently associated with neuropsychiatric symptoms (NPS) such as agitation and aggression, especially in the moderate to severe stages of the illness. The limited efficacy and high-risk profiles of current pharmacotherapies for the management of agitation and aggression in AD have driven the search for safer pharmacological alternatives. Over the past few years, there has been a growing interest in the therapeutic potential of medications that target the endocannabinoid system (ECS). The behavioural effects of ECS medications, as well as their ability to modulate neuroinflammation and oxidative stress, make targeting this system potentially relevant in AD. This article summarizes the literature to date supporting this rationale and evaluates clinical studies investigating cannabinoids for agitation and aggression in AD. Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids—dronabinol or nabilone—on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies. Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD.

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Correspondence to Nathan Herrmann.

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Conflict of interest

Krista L. Lanctôt has received research grants from the Alzheimer Drug Discovery Fund, the Alzheimer Society of Canada, the National Institute of Health, AbbVie, Lundbeck, Pfizer, Sanofi-Aventis, Janssen-Ortho Inc., and Roche and Wyeth, and honoraria from AbbVie, Pfizer, Janssen-Ortho Inc., and MedImmune. Nathan Herrmann has received research grants from the Alzheimer Drug Discovery Fund, the Alzheimer Society of Canada, the National Institute of Health, Canadian Institute of Health Research, Lundbeck, and Roche, and consultant fees from Lundbeck, AbbVie, and Eli Lilly. Celina S. Liu, Sarah A. Chau, and Myuri Ruthirakuhan report no conflicts of interest.

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This research was supported by the Alzheimer’s Drug Discovery Foundation (Grant 20140503) and the Alzheimer Society of Canada (Grant 15–17).

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Liu, C.S., Chau, S.A., Ruthirakuhan, M. et al. Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease. CNS Drugs 29, 615–623 (2015). https://doi.org/10.1007/s40263-015-0270-y

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Keywords

  • Nabilone
  • Dronabinol
  • Nocturnal Motor Activity
  • Microglial Phagocytic Function
  • Dronabinol Treatment