The researchers say that compared to current treatments for agitation, such as antipsychotics, dronabinol produced similar calming effects without adverse results such as delirium or seizures.

Results of the eight-year clinical trial were presented at the International Psychogeriatric Association conference in Buenos Aires, Argentina, on Sept. 26.”These new findings represent eight years of work dedicated to people who have Alzheimer’s as well as their caregivers,” says Paul Rosenberg, M.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and co-principal investigator for this study. “Agitation is one of the most distressing symptoms of Alzheimer’s dementia, and we are pleased to make positive strides forward in treatment of these patients.”

Alzheimer’s disease is the most common neurodegenerative disease in the United States, with an estimated 6.7 million cases in Americans age 65 and older, according to the National Institutes of Health. This number is predicted to grow to 13.8 million by 2060. Agitation is difficult to manage. It is defined as excess motor activity (pacing or repetitive movements), verbal aggression and/or physical aggression. An estimated 40% of people with Alzheimer’s develop agitation.

Although mild agitation can sometimes be moderated by behavioral intervention, in moderate to severe cases, some form of medication is typically required to manage symptoms and provide relief for caregivers.”It is the agitation, not the memory loss, that often drives individuals with dementia to the emergency department and long-term-care facilities,” says Brent Forester, M.D., psychiatrist-in-chief and chairman of the Department of Psychiatry at Tufts Medical Center and co-principal investigator on the study. “Dronabinol has the potential to both reduce health care costs and make an important, positive impact on caregivers’ mental and physical health.”

In the new study, researchers recruited 75 patients with severe Alzheimer’s agitation across five clinical sites, including 35 admitted to The Johns Hopkins Hospital between March 2017 and May 2024. To qualify, patients had to have a formal clinical diagnosis of Alzheimer’s disease and show at least one major symptom of agitation for at least two weeks. Prior to treatment, patients were tested for agitation using the Pittsburgh Agitation Scale (PAS) and the Neuropsychiatric Inventory Agitation/Aggression subscale (NPI-C).

The PAS scores agitation from 0 to 4, with 4 being the most agitated. The NPI-C provides a brief assessment of neuropsychiatric symptoms including delusions, hallucinations, anxiety/depression and other factors. Baseline scores were acquired from caregivers at the onset of the trial.

Participants were then randomly selected to get either 5 milligrams of dronabinol in pill form or a placebo in pill form twice daily for three weeks, and then retested using the PAS and NPI-C.

Results from the dronabinol group show an average PAS starting value of 9.68 and an end value of 7.26 after three weeks, a 30% decrease compared to the scores in the placebo group which did not change. Additionally, dronabinol was well tolerated by patients compared to current treatments for agitation.”Results like this are encouraging. We are thrilled that FDA-approved dronabinol was robustly effective and appeared safe for treatment of agitation,” says Rosenberg. “This adds another tool in our efforts to improve the care of our loved ones with Alzheimer’s disease.”

The researchers say they plan longer-term studies of dronabinol for Alzheimer’s disease, as well as expanded sample sizes. They also hope to continue to explore other ways medical cannabis can benefit both patients and caregivers.

Dronabinol is a synthetic form of THC, the psychoactive main ingredient in cannabis (marijuana). The drug was approved by the U.S. Food and Drug Administration in 1985 to treat loss of appetite in patients with HIV/AIDS, and is currently prescribed to treat nausea and vomiting in those undergoing cancer chemotherapy.

The investigators caution that their current study results are not intended to encourage or inform the use of other forms of medical marijuana available in 38 states and the District of Columbia.

Co-investigators include Halima Amjad, Haroon Burhanullah and Milap Nowrangi at the Johns Hopkins University School of Medicine, Marc Agronin at Miami Jewish Health, and James Wilkins and David Harper at McLean Hospital.

The study was funded by a grant from the National Institute of Aging at the National Institutes of Health.