Nabilone — a synthetic cannabinoid — reduced agitation and improved neuropsychiatric symptoms, cognition and nutrition in patients with moderate-to-severe Alzheimer’s disease, according to research presented at the 2018 Alzheimer's Association International Conference.
However, the researchers recommend the occurrence of sedation be closely monitored.
“Currently, an estimated 5.7 million Americans suffer from Alzheimer's disease and with the aging of the population, the absolute numbers are projected to rise. Agitation is common, has a negative impact on patients, and is challenging to treat. It is estimated that about half of the residents in long-term care facilities suffer from this symptom, which increases falls, weight loss and mortality and strongly decreases quality of life,” Krista Lanctôt, PhD, from Sunnybrook Research Institute in Toronto, told Healio Psychiatry. “Unfortunately, there are currently no treatments that work well and have a good safety profile. The group of medications that work the best increase mortality. We sought to find a new medication for this important and growing problem.”
In this 14-week, randomized, double-blind, placebo-controlled cross-over trial, the investigators assessed the efficacy and safety of nabilone for the treatment of agitation in moderate-to-severe Alzheimer’s disease. Lanctôt and colleagues allocated 39 older adults (average age 87 years) to receive 6 weeks of nabilone (1 mg to 2 mg) followed by placebo, with a 1-week washout between each treatment period. The researchers assessed agitation, as measured by the Cohen-Mansfield Agitation Inventory, along with safety, overall neuropsychiatric symptoms, cognition and global impression. They also examined pain and nutritional status as exploratory outcomes.
The results showed that agitation improved significantly in older adults with Alzheimer’s disease who received nabilone compared with placebo (b = –4; 95% CI, –6.5 to –1.5; P = .003). In addition, nabilone had no cross-over or treatment-order effects. However, more participants experienced sedation on nabilone than placebo (45% vs. 16%; P = .02).
“We found a robust and significant decrease in agitation during nabilone compared to placebo, a significant overall improvement and a decrease in caregiver distress,” Lanctôt said. “We also found increased sedation in those on nabilone, and questions remain about its effect on cognition.”
The researchers also observed significant differences in Neuropsychiatric Inventory-agitation/aggression (b = –1.5; 95% CI, –2.3 to –0.6; P = .001), overall neuropsychiatric symptoms (b = –4.6; 95% CI, –7.5 to –1.6; P = .004) and cognition (b = 1.1; 95% CI, 0.1-2; P = .026) favoring nabilone. Moreover, 47% and 23% of patients showed improvement on the global impression scale during the nabilone and placebo phases. There were also small benefits to nutritional status on nabilone, but not to pain.
“This is the first clinical trial to show that a cannabinoid can decrease agitation in Alzheimer's disease. It opens the door for further research in this area and provides a signal that this may be a future therapy,” Lanctôt told Healio Psychiatry. “A single trial is not sufficient evidence to change clinical practice. Results do not speak to the use of medical marijuana or other synthetic versions of [tetrahydrocannabinol].” – by Savannah Demko
Lanctôt K, et al. Nabilone significantly improves agitation/aggression in patients with moderate-to-severe AD: Preliminary results of a placebo-controlled, double-blind, cross-over trial. Presented at: Alzheimer's Association International Conference; July 22-26, 2018, 2018; Chicago.
Disclosure: Lanctôt reports that this study was supported by The Alzheimer's Drug Discovery Foundation and the Alzheimer's Society of Canada.