Researchers have discovered that a pill version of dronabinol, a synthetic drug approved by the FDA that mimics the primary active ingredient in marijuana, THC, can reduce agitation in patients with Alzheimer’s by approximately 30%.
Researchers have found that a pill version of dronabinol, an FDA-approved synthetic version of THC, the main compound in marijuana, reduces agitation in Alzheimer’s patients by about 30%.
The research indicates that dronabinol offers calming effects similar to those of existing agitation treatments like antipsychotics but does not produce negative side effects such as delirium or seizures.
Findings from an extensive eight-year clinical trial were shared at the International Psychogeriatric Association conference in Buenos Aires, Argentina, on September 26. “These important findings are the result of eight years of dedicated work for those affected by Alzheimer’s and their caregivers,” said Paul Rosenberg, M.D., a professor of psychiatry and behavioral sciences at Johns Hopkins University and one of the primary investigators for this study. “Agitation is one of the most troubling symptoms of Alzheimer’s dementia, and we are encouraged by our progress in treating these patients.”
According to the National Institutes of Health, Alzheimer’s disease is the most widespread neurodegenerative condition in the U.S., affecting approximately 6.7 million individuals aged 65 and older. This figure is projected to rise to 13.8 million by the year 2060. Managing agitation can be particularly challenging. It is characterized by excessive motor activity (like pacing or repetitive motions), as well as verbal or physical aggression. Around 40% of individuals with Alzheimer’s experience agitation.
While minor agitation can sometimes be alleviated through behavioral strategies, moderate to severe cases often necessitate medication to help manage symptoms and ease the burden on caregivers. “It is often the agitation—not the memory loss—that leads dementia patients to visit emergency rooms or enter long-term care facilities,” stated Brent Forester, M.D., psychiatrist-in-chief and head of Psychiatry at Tufts Medical Center and another co-principal investigator on the study. “Dronabinol holds the promise of reducing healthcare expenses while positively impacting the well-being of caregivers.”
In this study, 75 patients experiencing severe agitation due to Alzheimer’s were recruited from five clinical sites, including 35 admitted to The Johns Hopkins Hospital between March 2017 and May 2024. To be included in the study, patients needed a formal diagnosis of Alzheimer’s disease and had to exhibit at least one significant symptom of agitation for a minimum of two weeks. Before treatment began, agitation levels were assessed using the Pittsburgh Agitation Scale (PAS) and the Neuropsychiatric Inventory Agitation/Aggression subscale (NPI-C).
The PAS rates agitation from 0 to 4, with 4 indicating the highest level of agitation. The NPI-C offers a brief evaluation of neuropsychiatric symptoms such as delusions, hallucinations, and anxiety or depression. Caregivers provided baseline scores at the start of the trial.
Participants were then randomly assigned to receive either 5 milligrams of dronabinol or a placebo in pill form, administered twice daily for three weeks. They were retested using the PAS and NPI-C at the end of this period.
The group receiving dronabinol showed a starting PAS score of 9.68, which decreased to 7.26 after three weeks—a 30% drop. In contrast, scores in the placebo group remained unchanged. Moreover, patients tolerated dronabinol better compared to existing agitation treatments. “These outcomes are promising. We are excited that FDA-approved dronabinol proved to be both effective and safe for treating agitation,” said Rosenberg. “This provides another valuable option in enhancing care for individuals with Alzheimer’s disease.”
The researchers intend to conduct longer-term studies on dronabinol for Alzheimer’s and to increase sample sizes. They also aim to investigate additional ways medical cannabis could benefit patients and caregivers.
Dronabinol is a synthetic derivative of THC, the active psychoactive component in cannabis. The drug received FDA approval in 1985 for treating appetite loss in patients with HIV/AIDS and is now also prescribed for nausea and vomiting associated with cancer chemotherapy.
The researchers caution that the results of their current study should not encourage the use of other medical marijuana forms available in 38 states and the District of Columbia.
Other co-investigators include Halima Amjad, Haroon Burhanullah, and Milap Nowrangi from Johns Hopkins, as well as Marc Agronin from Miami Jewish Health and James Wilkins and David Harper from McLean Hospital.
This study was supported by a grant from the National Institute of Aging at the National Institutes of Health.
