A new randomized controlled trial by Rosenberg and colleagues offers encouraging evidence that dronabinol, an oral synthetic THC, may be a safe and effective treatment option for agitation in Alzheimer’s disease. In this 3-week, double-blind study of 75 participants with moderate to severe dementia, dronabinol (titrated to 10 mg/day in divided doses) significantly reduced agitation on the Pittsburgh Agitation Scale compared with placebo, demonstrating a moderate effect size (0.53).

A second co-primary measure, the NPI-C Agitation/Aggression domain, showed a nonsignificant trend toward improvement.

Importantly, the population was highly representative of real-world dementia care—severely cognitively impaired, ethnically diverse, and commonly receiving concomitant psychotropics—enhancing the clinical applicability of results.

Dronabinol was generally well tolerated, with somnolence as the only adverse effect more common than placebo, and no meaningful differences in delirium, falls, intoxication, or cognitive decline. Secondary outcomes, including sleep, Activities of Daily Living (ADLs), and Cohen-Mansfield Agitation Inventory (CMAI) scores, showed no significant differences.

While the short duration and small sample size limit broader conclusions, these findings suggest that dronabinol may serve as a useful adjunctive option for agitation, particularly when behavioral measures are insufficient and antipsychotic risks are prohibitive.

Further research is needed to evaluate longer-term efficacy and safety, but this study provides an important addition to the evolving landscape of pharmacologic strategies for managing agitation in Alzheimer’s disease.

Reference:
Rosenberg PB et al. Am J Geriatr Psychiatry. 2026;34(2):167-179. Abstract