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CHICAGO -- Nabilone, a synthetic cannabinoid, improved symptoms of agitation and aggression among Alzheimer's disease patients, researchers reported here.

Nabilone (Cesamet) is currently approved for the treatment of chemotherapy-related nausea and vomiting. The oral agent offered clinically and statistically significant improvements in agitation compared with placebo measured by the Cohen-Mansfield Agitation Inventory (treatment difference b= -4.0, 95% CI -6.5 to -1.5, P=0.003), according to Krista Lanctôt, PhD, of the Sunnybrook Research Institute in Toronto, and colleagues.

The authors also reported other significant treatment benefits with nabilone compared with placebo over the 14-week cross-over trial, which was presented at the Alzheimer's Association International Conference:

• Neuropsychiatric Inventory agitation/aggression score: b= -1.5 (95% CI -2.3 to -0.6, P=0.001)
• Overall neuropsychiatric symptoms: b= -4.6 (95% CI -7.5 to -1.6, P=0.004)
• Cognition: b= 1.1 (95% CI 0.1-2.0, P=0.026)
• Nutrition: b= 0.2 (95% CI 0.02-0.4, P=0.03)

Similarly, as measured by the Clinician's Global Impression of Change, more patients saw an improvement in symptoms while on nabilone (47% versus 23% with placebo, McNemar's test, P=0.09).

"Agitation and aggression are common in those with Alzheimer's disease, and have a negative impact on patients and caregivers alike," Lanctôt explained to MedPage Today. "While nondrug interventions are tried first, many people do not respond. Unfortunately, current drug treatments are not very effective and increase mortality, meaning that these treatments are used only very judiciously."

"We know that cannabis and related synthetic medications can have calming effects, increase appetite, and decrease pain -- all of which might be helpful in those with Alzheimer's disease suffering from agitation," she added. "However, we did not know if these medications would be helpful in this group of patients. For those reasons, the [current study] results are both predictable, and surprising."

The randomized, double-blind trial included 39 individuals with moderate to severe Alzheimer's disease and who experienced agitation. As a non-cognitive symptom, Lanctôt highlighted that it's relatively common among those with moderate or severe Alzheimer's disease, with around 20% to 50% of these patients experiencing it.

Participants randomized to receive nabilone for 6 weeks achieved a target therapeutic dose range between 1 to 2 mg. After a 1-week washout period, trial participants crossed over treatment groups and continued for another 6 weeks, followed by another washout week. Improvements in cognition were measured by the standardized Mini-Mental Status Exam.

Sedation was also more common when on nabilone treatment (45% versus 16% placebo, McNemar's test, P=0.02), although there was no significant difference in treatment-limiting sedation. Pain experience also remained unchanged with treatment (b= 0.03, 95% CI -0.22 to 0.27, P=0.8).

"It does have some of the euphoric effects that you'd see with cannabinoids, as well as some of the drowsiness and sleepiness side-effects," commented Heather Snyder, PhD, senior director of medical and scientific operations for the Alzheimer's Association.

"However, the study authors do talk quite a bit about the balance of that with the potential benefits of [nabilone]," she told MedPage Today. Snyder, who was not involved in the study, highlighted how an improvement in agitation also translates to an overall improvement in the quality-of-life for these individuals.

Benefits of the treatment went beyond the individual, with caregiver distress also showing a meaningful reduction, Lanctôt stated.

"We are encouraged by the results, but recognize that this study was done in a small number of patients. Larger trials and replication will be needed to make recommendations that would change clinical practice," she concluded.

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