Agitation is a prevalent and difficult-to-treat symptom in patients with moderate-to-severe
Alzheimer's disease (AD). Though there are nonpharmacological and pharmacological interventions recommended for the treatment of agitation, the efficacy of these are modest and not always consistent. Furthermore, the safety profiles of currently prescribed medications are questionable.
Nabilone, a synthetic
cannabinoid, has a distinct pharmacological profile that may provide a safer and more effective treatment for agitation, while potentially having benefits for weight and
pain. Additionally, emerging evidence suggests
nabilone may have
neuroprotective effects. We describe a clinical trial investigating the safety and efficacy of
nabilone for the treatment of agitation in patients with moderate-to-severe AD. This will be a double-blind, randomized cross-over study comparing 6 weeks of
nabilone (0.5-2 mg) and placebo, with a 1-week washout preceding each phase. Study outcomes will be measured at baseline and end of treatment for each treatment phase. The primary outcome measure will be agitation as assessed by the Cohen-Mansfield Agitation Inventory. The secondary outcomes include safety, behaviour (Neuropsychiatric Inventory), cognition (standardized Mini Mental Status Exam and either Severe Impairment Battery or
Alzheimer's disease Assessment Scale-Cognitive subscale) and global impression (Clinician's Global Impression of Change). Exploratory outcomes include
pain (
Pain Assessment in Advanced AD), nutritional status (Mini-Nutritional Assessment-Short Form), caregiver distress (NPI caregiver distress), and blood-based
biomarkers. A safe and efficacious pharmacological intervention for agitation, with effects on
pain and
weight loss in patients with moderate-to-severe AD could increase quality-of-life, reduce caregiver stress and avoid unnecessary
institutionalization and related increases in health care costs.
CLINICAL TRIALS NUMBER: NCT02351882.