In a study led by Johns Hopkins University School of Medicine and Tufts University School of Medicine, researchers show that a pill form of the drug dronabinol, an FDA-approved synthetic version of marijuana’s main ingredient, THC, reduces arousal in patients with Alzheimer’s disease reduces by an average of 30%.
The researchers say that compared to current treatments for agitation such as antipsychotics, dronabinol produced similar calming effects without adverse effects such as delirium or seizures.
The results of the eight-year clinical trial were presented on September 26 at the International Psychogeriatric Association conference in Buenos Aires, Argentina.
These new findings represent eight years of work dedicated to people with Alzheimer’s disease and their caregivers. Agitation is one of the most troubling symptoms of Alzheimer’s disease, and we are pleased to be making positive progress in treating these patients.”
Paul Rosenberg, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine and co-principal investigator for this study
According to the National Institutes of Health, Alzheimer’s disease is the most common neurodegenerative disease in the United States, with an estimated 6.7 million cases among Americans age 65 and older. This number is predicted to grow to 13.8 million by 2060. Agitation is difficult to control. It is defined as excessive motor activity (paced or repetitive movements), verbal aggression and/or physical aggression. An estimated 40% of people with Alzheimer’s disease develop agitation.
Although mild agitation can sometimes be moderated with behavioral intervention, moderate to severe cases typically require some form of medication to control symptoms and provide relief to caregivers. It is the agitation, not the memory loss, that often drives people with dementia to emergency departments and long-term care facilities,” said Brent Forester, MD, psychiatrist-in-chief and chairman of the Department of Psychiatry at Tufts Medical Center and co-principal investigator of the study. “Dronabinol has the potential to both reduce healthcare costs and have a significant, positive impact on the mental and physical health of healthcare providers.”
In the new study, researchers recruited 75 patients with severe Alzheimer’s agitation at five clinical sites, including 35 who were admitted to Johns Hopkins Hospital between March 2017 and May 2024. To be eligible, patients had to have a formal clinical diagnosis of Alzheimer’s disease and present with at least one major symptom of agitation for at least two weeks. Before 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 obtained from healthcare providers at the start of the study.
Participants were then randomly selected to receive 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 a final value of 7.26 after three weeks, a decrease of 30% compared to the scores in the placebo group, which did not change. Furthermore, dronabinol was well tolerated by patients compared to current treatments for agitation. “These types of results are encouraging. We are pleased that FDA-approved dronabinol was robustly effective and appeared safe for the treatment of agitation,” says Rosenberg. “This adds another tool to our efforts to improve care for 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 exploring other ways in which medical cannabis can benefit both patients and healthcare providers.
Dronabinol is a synthetic form of THC, the main psychoactive 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 people undergoing chemotherapy for cancer.
The researchers 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 of Johns Hopkins University School of Medicine, Marc Agronin of Miami Jewish Health, and James Wilkins and David Harper of McLean Hospital.
The study was funded by a grant from the National Institute of Aging of the National Institutes of Health.