The experimental combination of tetrahydrocannabinol (THC) plus cannabidiol (CBD) proves beneficial in reducing agitation in hospice care-eligible patients with late-stage dementia, according to the phase II LiBBY trial.
LiBBY met its primary endpoint, with Cohen-Mansfield Agitation Inventory (CMAI) scores at week 2 decreasing significantly more with THC/CBD than with placebo (–10.61 vs –4.35 points; p=0.0004), reported Dr Jacobo Mintzer from the Medical University of South Carolina in Charleston, South Carolina, US. [Mintzer J, et al, AAIC 2026]
CMAI scores continued to decrease through week 12 among THC/CBD-treated patients, with a mean area under the curve contrast of –8.23 points (95 percent confidence interval, –11.6 to –4.86) between the THC/CBD and placebo groups (p<0.0001), he added.
Mintzer noted that the changes in CMAI scores aligned with blinded clinician assessments. At week 2, 83.9 percent of patients in the THC/CBD group improved on the Clinical Global Impression of Change in Behavior scale compared with 30.5 percent in the placebo group. This difference became more pronounced by week 12, at 87.2 percent vs 23.6 percent.
In terms of safety, “the THC/CBD intervention was well tolerated by most patients,” he said.
Adverse event (AE) rates were similar between the intervention and placebo groups (46.7 percent vs 42.4 percent). Serious AEs occurred in 23.3 percent of THC/CBD-treated patients and in 11.9 percent of those who received placebo. Death rates were higher in the THC/CBD group (13.1 percent vs 5.1 percent), but no specific patterns emerged for the cause of death, as Mintzer pointed out.
A major step forward
“This is a robustly positive, randomized, controlled trial that represents a major step forward in treatment for a population that has been historically overlooked in clinical research,” Mintzer said.
He pointed out that agitation is a major concern in this population, as it deprives patients from spending the last few days or weeks of their life in peace and with dignity. “We now have evidence supporting a new and very effective treatment approach for this neuropsychiatric symptom.”
“The findings only apply to the specific THC/CBD compound tested in the trial and not to any other forms of cannabis or publicly available marijuana,” he added.
Mintzer also highlighted a key methodological lesson from the trial, saying that patients must be treated in their own environments and should not be required to travel to a clinic. For an agitated patient, taking a trip can introduce temporary distress, which may in turn affect the drug’s efficacy, he explained. “If we’re going to treat agitation in patients, we should treat patients where they are.”
The LiBBY trial
LiBBY was a double-blind, placebo-controlled trial that involved 120 patients (mean age 80 years, 55 percent female, 84 percent White) with Alzheimer’s disease or other types of dementia who were experiencing agitation. Patients had to be currently enrolled in inpatient/outpatient hospice care, have a Functional Assessment Staging Tool score of at least 6D, and/or have an Advanced Dementia Prognostic Tool score of at least 12. Additionally, patients were required to reside in a suitable environment, where research could be successfully conducted.
The patients were randomized to receive treatment with a purified THC/CBD compound (n=61) or placebo (n=59), administered orally twice daily at the patients’ homes or place of residence for 12 weeks. The THC/CBD compound contained 4 mg of THC and 200 mg of CBD dissolved in digestible oil. This formulation, according to Mintzer, is not publicly available and is not used for any other indication.
Mintzer shared that his team plans on testing the THC/CBD compound in a broader study population.
“LiBBY directly addresses one of the most challenging and under-discussed aspects of Alzheimer’s disease—end-of-life agitation,” commented Alzheimer’s Association VP of Care & Support Dr Elizabeth Edgerly, who was not involved in the trial.
“These results not only highlight a promising therapeutic option but also underscore the importance of prioritizing attention, care, and research for individuals in mid- and late-stage Alzheimer’s and related dementias,” Edgerly added.