Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer's Disease.
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.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 19, Toronto, ON, M4N 3M5, Canada.
Celina S
CS
Liu
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 19, Toronto, ON, M4N 3M5, Canada.
Sarah A
SA
Chau
Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 19, Toronto, ON, M4N 3M5, Canada.
Myuri
M
Ruthirakuhan
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 19, Toronto, ON, M4N 3M5, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Krista L
KL
Lanctôt
Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 19, Toronto, ON, M4N 3M5, Canada. nathan.herrmann@sunnybrook.ca.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada. nathan.herrmann@sunnybrook.ca.
Nathan
N
Herrmann
D000374:Aggression / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D063388:Endocannabinoids / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology
D002186:Cannabinoids; D063388:Endocannabinoids