Predicting Response to Cannabinoid Treatment for Agitation in Alzheimer Disease: Krista L. Lanctôt, PhD

WATCH TIME: 4 minutes

"The more of these predictors you have, the more likely you were to respond...88% of [patients] with more predictors responded, compared to less than a third with fewer predictors."

Years of research has shown that agitation is one of the most common neuropsychiatric symptoms in Alzheimer disease (AD), which can typically be managed with atypical antipsychotics that may carry notable risks for older adults. In more recent studies, cannabis-based medications have been explored for their potential to address agitation and related comorbidities by modulating neurotransmitters and reducing neuroinflammation.¹ For example, a recently conducted randomized, placebo-controlled crossover trial demonstrated that nabilone, a synthetic cannabinoid, effectively reduced agitation among patient with AD^.2

New data presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain, revealed that patients with AD who experienced pain, irritability, depressive symptoms and appetite changes, and who also had less cognitive impairment and were not on concomitant cholinesterase inhibitors, were more highly likely to benefit from nabilone compared with placebo. These findings were consistent with the expected benefits of cannabinoids from previous studies and if confirmed further in additional research, these predictors could be useful as a guide for clinicians to help them see who would most likely benefit from nabilone as an alternative therapy for management of agitation in AD.³

At the conference, senior author of the study Krista L. Lanctôt, PhD, professor of psychiatry and pharmacology at the University of Toronto, sat down with NeurologyLive^® to elaborate on the significance of the clinical predictors identified for nabilone response in Alzheimer agitation treatment. She also spoke about the role she believed that cognitive status and concomitant symptoms such as pain and irritability play in mediating the response to cannabinoid therapy. Moreover, Lanctôt talked about how the observed interaction between concomitant cholinesterase inhibitor use and response to nabilone might impact clinical guidelines for using cannabinoids in this patient population.

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REFERENCES
1. Outen JD, Burhanullah MH, Vandrey R, et al. Cannabinoids for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2021;29(12):1253-1263. doi:10.1016/j.jagp.2021.01.015
2. Herrmann N, Ruthirakuhan M, Gallagher D, et al. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2019;27(11):1161-1173. doi:10.1016/j.jagp.2019.05.002
3. Feldman OJ, Ruthirakuhan M, Herrmann N, et al. Heterogeneity of treatment response: A post hoc analysis of clinical factors from a randomized placebo-controlled trial of nabilone for agitation in Alzheimer’s disease. Presented at: 2024 CTAD; October 29-November 1; Madrid, Spain. LBS4. Presentation 1.