Dronabinol May Have a Role for Quelling Agitation in Alzheimer Disease: New Data

Oral dronabinol reduced Alzheimer agitation by 30% in a study of adults with severe symptoms who received the treatment for 3 weeks. The improvements observed were similar to the calming effects of current treatments for agitation, such as antipsychotic medications, but without the common adverse events, which can include delirium and seizures, according to the study authors, from Johns Hopkins University School of Medicine and Tufts University School of Medicine.

Results of the 8-year clinical trial were presented at the International Psychogeriatric Association conference in Buenos Aires, Argentina, on September 26. “These new findings represent eight years of work dedicated to people who have Alzheimer’s as well as their caregivers,” Paul Rosenberg, MD, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and co-principal investigator for this study said in a news release. “Agitation is one of the most distressing symptoms of Alzheimer’s dementia, and we are pleased to make positive strides forward in the treatment of these patients.”

Rosenberg and colleagues recruited 75 adults with severe Alzheimer agitation across 5 clinical sites, a cohort that included 35 admitted to The Johns Hopkins Hospital between March 2017 and May 2024. Qualification for the study required a formal clinical diagnosis of Alzheimer disease and at least 1 major symptom of agitation for at least 2 weeks. At study baseline, participants were evaluated 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.

“Agitation is one of the most distressing symptoms of Alzheimer’s dementia, and we are pleased to make positive strides forward in the treatment of these patients.”

The researchers then randomly assigned participants to receive either 5 milligrams of dronabinol in pill form or a placebo in pill form twice daily for 3 weeks. The full cohort was re-evaluated using the the PAS and NPI-C.

Findings. Results from the dronabinol group show an average PAS starting score of 9.68 and an end value of 7.26 after 3 weeks, a 30% decrease compared to the scores in the placebo group which did not change during the study. The researchers emphasized that dronabinol was well tolerated by all participants. “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.”

Alzheimer Agitation

According to the Alzheimer Association, Alzheimer disease is the most common neurodegenerative disease in the United States. The association estimates the disease affects 6.7 million Americans aged 65 years and older and predicts the number will increase to 13.8 million by 2060. Agitation in people with Alzheimer disease is defined as excess motor activity (pacing or repetitive movements), verbal aggression, and/or physical aggression and is difficult to manage. An estimated 40% of people with Alzheimer develop agitation.

Mild agitation can sometimes be moderated by behavioral intervention, Rosenberg et al wrote. In moderate to severe cases, however, 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,” Brent Forester, MD, psychiatrist-in-chief and chairman of the Department of Psychiatry at Tufts Medical Center and co-principal investigator on the study, said in the news release. “Dronabinol has the potential to both reduce health care costs and make an important, positive impact on caregivers’ mental and physical health.”

“It is the agitation, not the memory loss, that often drives individuals with dementia to the emergency department and long-term-care facilities.”

Rosenberg, Forester, and colleagues are planning larger and longer-term studies of dronabinol for Alzheimer disease, they said. Exploration of other applications for medical cannabis for both individuals with Alzheimer dementia and their caregivers is also of interest to the team.

Dronabinol is a synthetic form of THC, the psychoactive main ingredient in cannabis (marijuana). The drug was approved by the US FDA 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.

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

1. Clinical trial shows synthetic cannabis reduces agitation in Alzheimer disease. News release. Johns Hopkins University School of Medicine. October 2, 2024. Accessed October 7, 2024. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/10/clinical-trial-shows-synthetic-cannabis-reduces-agitation-in-alzheimers-disease

2. 2023 Alzheimer’s disease facts and figures. A&D. 2023;19(4):1598-1695. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13016