CHICAGO — The synthetic cannabinoid nabilone significantly reduces agitation in patients with moderate to severe Alzheimer's disease (AD), results of a small randomized controlled trials show.
Nabilone had the "calming effect that we were hoping for," Krista Lanctot, PhD, from Sunnybrook Health Sciences Center and the University of Toronto, Canada, said during a press briefing here at the Alzheimer's Association International Conference (AAIC) 2018.
Up to half of patients with AD will experience agitation at some point in their illness. It's distressing for patients and their caregivers and remains a "major treatment challenge," she added.
The US Food and Drug Administration has not approved any drug treatments for agitation in patients with dementia associated with AD. Antipsychotics used off label are only modestly effective and come with significant side effects, including an increased risk for death. There is an "urgent need for safer medication options," said Lanctot.
Nabilone is approved in the United States to treat nausea and vomiting in cancer patients. In other countries, such as Canada, it is used as an adjunct therapy for the management of chronic pain.
Hoping to repurpose the drug for AD-related agitation, the investigators tested the effects of nabilone (1 to 2 mg daily) in 39 patients (mean age, 87 years; 77% male) with moderate to severe AD (standardized Mini–Mental Status Examination score ≤24) and clinically significant agitation (Neuropsychiatric Inventory [NPI]–agitation/aggression subscore ≥3). Most of the patients were living in long-term care facilities and had failed to respond to several medications.
Clear Calming Effect
In the 14-week crossover study, patients received nabilone capsules (mean therapeutic dose, 1.6 mg) for 6 weeks, followed by placebo for 6 weeks, with 1 week between each treatment period.
Agitation improved significantly in those taking nabilone compared to those taking placebo, as measured by the Cohen-Mansfield Agitation Inventory (P = .003). Of note, said Lanctot, 47% of patients experienced improvement on the Clinician's Global Impression of Change scale while taking nabilone, whereas 23% experiened improvement while taking placebo.
Nabilone also significantly improved overall behavioral symptoms in comparison with placebo, as measured by the NPI (P = .004). There was also a decrease in caregiver distress during nabilone treatment.
Some patients had decreased cognition during nabilone. "That is a side effect that we are concerned about and we still have questions about," Lanctot said. Also, more patients experienced sedation with nabilone than with placebo (45% vs 16%), but "we used that to adjust the medication dose, and it wasn't treatment limiting," said Lanctot.
This is the first clinical trial of nabilone for agitation in AD, she noted, "and we think this opens the door" for the use of cannabinoids in treating agitation in patients with AD. However, a larger trial is needed to further assess efficacy and safety of nabilone for agitation in AD. That trial is now in the planning stages.
Huge Unmet Need
"The results of this research are very encouraging especially given the numerous failures in the field to date," Howard Fillit, MD, founding executive director and chief science officer, Alzheimer's Drug Discovery Foundation, told Medscape Medical News.
"The use of synthetic cannabinoids is a novel approach in the treatment of agitation in patients with Alzheimer's and fills a huge unmet medical need. There is great interest and excellent scientific rationale for the use of cannabinoids in Alzheimer's that might include a disease-modifying effect that can be tested in subsequent studies," said Fillit.
In an interview with Medscape Medical News, Eric Reiman, MD, executive director, Banner Alzheimer's Institute, Phoenix, Arizona, cautioned that although these are "encouraging preliminary data in a small sample, [nabilone] needs to be put to the test in larger, more definitive trials."
Heather Snyder, PhD, senior director of medical and scientific operations at the Alzheimer's Association, told Medscape Medical News that new ways to address noncognitive symptoms of Alzheimer's and dementia "need to be explored, because noncognitive symptoms play such a significant role not only in the patient's quality of life but also in the quality of life of their carer or family. We absolutely need more effective treatments.
"While we are doing quite a bit of work in terms of preventing and slowing the progression of the disease, we also need to be thinking about patients in their day-to-day lives as well," said Snyder.
For the treatment of dementia-related behaviors, the Alzheimer's Association currently recommends nonpharmacologic approaches, such as psychosocial interventions, as first-line alternatives to pharmacologic therapy.
Psychosocial interventions include validation therapy (validating that the person seems to be upset over something and separating the person from what seems to be upsetting); engaging in regular physical activity to potentially reduce irritability and aggressive behavior; and assessing for the presence of pain, constipation, or another physical problems.
Funding for the study was provided by the Alzheimer's Drug Discovery Foundation and the Alzheimer Society of Canada Research Program. The authors have disclosed no relevant financial relationships.
Alzheimer's Association International Conference (AAIC) 2018. Abstract F4-02-04, presented July 24, 2018.
Medscape Medical News © 2018
Cite this: Synthetic Cannabinoid Cuts Agitation in Alzheimer's Disease - Medscape - Jul 25, 2018.