Dronabinol for the Treatment of Agitation in Alzheimer's Disease: A Mini-Review
Surafel Tsegaye1, Brent P. Forester1, Paul B. Rosenberg2*
1Department of Psychiatry, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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 PdfCommentary to Neuroinflammation and osteomyelitis in adults with Type 2 diabetes mellitus and peripheral neuropathy without and with foot lesions. What comes first?
DOI: 10.29245/2572.942X/2026/1.1330 View / Download PdfMaria Sambataro1*, Francesca Pitzalis1, Matteo Fassan2, Marco Segatto3
1Endocrine, Metabolism and Nutrition Disease Unit, Santa Maria di Ca’ Foncello Hospital, Treviso, Italy
2Department of Pathology, University of Padua and Veneto Institute of Oncology IRCCS, Italy
3Department of Biosciences and Territory, University of Molise, Italy