Dronabinol for the Treatment of Agitation in Alzheimer's Disease: A Mini-Review
Background: Neuropsychiatric symptoms affect up to 70% of individuals with dementia and place a heavy burden on patients, carers and health care systems. Current pharmacological therapies have historically centered on SSRIs and antipsychotics, which carry a black box warning on increased mortality from all causes in patients with dementia. Two FDA-approved treatments for agitation in AD now exist, brexpiprazole (2023) and Auvelity/dextromethorphan-bupropion (2026), yet limitations persist and the need for additional well-tolerated options remains.
Objective: The endocannabinoid system (ECS) has emerged as a promising therapeutic target. This review assesses the clinical evidence supporting the use of dronabinol (synthetic delta 9-tetrahydrocannabinol; THC) for the treatment of agitation in Alzheimer's disease and reviews the literature on the recently completed randomized controlled trial THC-AD.
Methods: A narrative review of PubMed and ClinicalTrials.gov was conducted through February 2026 using the keywords dronabinol, agitation, Alzheimer's disease, and cannabinoids.
Results: The review included results from open-label pilot studies, a crossover randomized clinical trial (RCT) with nabilone and a multicenter parallel group RCT (THC-AD). The THC-AD study demonstrated a clinically relevant reduction in agitation as measured by the Pittsburgh Agitation Scale (PAS; p=0.015; ES = 0.53 per week). Dronabinol was generally well-tolerated, with somnolence identified as the only notable side effect occurring at a higher frequency in the treatment group than in the placebo group.
Conclusions: Accumulating clinical evidence supports the need for a more definitive Phase III trial to establish dronabinol as a viable and potentially approvable treatment for agitation in Alzheimer's disease. Dronabinol's distinct endocannabinoid mechanism, favorable safety profile, and absence of antipsychotic-class mortality risk position it as a complementary option within a treatment landscape that now includes brexpiprazole and Auvelity (dextromethorphan HBr/bupropion HCl).
DOI: 10.29245/2572.942X/2026/1.1332 View / Download Pdf