A combination of CBD and THC rapidly and significantly reduces agitation in hospice-eligible people with dementia, suggest topline results from the Phase 2 LiBBY (Life's End Benefits of cannaBidiol and tetrahYdrocannabinol) clinical trial. The findings were reported for the first time at the Alzheimer's Association International Conference 2026 in London and online.
"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," said lead investigator Dr. Jacobo Mintzer, psychiatrist at the Ralph H. Johnson VA Healthcare System and professor, College of Health Professions, Medical University of South Carolina. "We now have evidence supporting a new and very effective treatment approach for agitation that may be appropriate for people in the final stages of dementia at the end of life, offering them grace and peace in what is often an extremely difficult time for patients and their families."
The multicenter, randomized, double-blind, placebo-controlled study evaluated a novel oral formulation (2 mg THC/100 mg CBD dissolved in digestible oil, provided twice a day) in 120 participants with dementia who were eligible for or received hospice care and were experiencing clinically significant agitation. The trial achieved its primary and key secondary endpoints.
Key findings:
- At Week 2, participants receiving THC/CBD showed a 6.27-point greater reduction in agitation scores than those receiving placebo, which was statistically significant, indicating rapid symptom relief.
- Benefits were sustained through Week 12, with participants receiving THC/CBD experiencing an 8.23-point greater reduction in agitation than those receiving placebo.
- Clinician-rated global improvement:
- Week 2: 83.9% of treated participants improved vs. 30.5% on placebo.
- Week 12: 87.2% of treated participants improved vs. 23.6% on placebo.
Overall adverse event rates were similar between groups (46.7% vs. 42.4%). Over 12 weeks, 23.3% of participants in the treatment arm experienced serious adverse events, compared with 11.9% in the placebo arm. Investigators determined that none of the serious adverse events were related to the study medication.
"People with advanced dementia, particularly those nearing the end of life, have historically been underrepresented in clinical research, despite the profound challenges faced by patients, families and caregivers," said Dr. Jeff Keller, Director of the Institute for Dementia Research and Prevention at Pennington Biomedical Research Center and principal investigator of the Pennington Biomedical LiBBY study site. "The LiBBY study demonstrates that it is possible to conduct rigorous clinical trials with this population and, importantly, that doing so can lead to meaningful advances in care. The magnitude and speed of the reduction in agitation we observed with the THC/CBD combination were remarkable. These results address a significant unmet medical need and offer new hope for providing greater comfort and dignity to people with advanced dementia at the end of life."
Agitation affects about half of people living with dementia near the end of life, and more than one-third continue to experience symptoms despite off-label treatment with benzodiazepines, opioids and antipsychotics – therapies that can be difficult to manage and carry significant risks.
In severe dementia and in the late stages of life, agitation is a common neuropsychiatric symptom characterized by emotional distress, excessive motor activity, and verbal or physical tension. Because individuals in the late stages of dementia, especially toward the end of life, often lose their ability to communicate effectively, agitation frequently serves as a direct behavioral signal of physical discomfort, fear or unmet needs. Symptoms – which may be distressing to patients, families and caregivers – may include:
- Pacing or wandering
- Fidgeting and repetitive movements
- Loud, sudden vocal outbursts or calling out continuously
- Repetitive phrases
- Moaning or groaning
- Verbal hostility
- Hitting, kicking, scratching, biting or pushing others
- Throwing or destroying property
The LiBBY study directly addresses one of the most challenging and under-discussed aspects of Alzheimer's disease – end-of-life agitation. 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."
Dr. Elizabeth Edgerly, Alzheimer's Association vice president of Care and Support
The Alzheimer's Association supports a careful, individualized approach to managing behavioral and psychological symptoms of dementia, and encourages patients, caregivers and clinicians to review the prescribing information carefully and engage in shared decision-making when considering treatment. Nonpharmacological strategies, including environmental modifications, structured routines and psychosocial interventions, are recommended as a first-line approach.
LiBBY, which was conducted by the National Institute on Aging (NIA)-funded Alzheimer's Clinical Trial Consortium (ACTC), is among the first randomized, controlled trials in a hospice-eligible population with dementia.
The LiBBY trial was a 12-week, Phase 2 study conducted across multiple U.S. sites. Participants with Alzheimer's or another disease that causes dementia and significant agitation were randomized to receive either the THC/CBD combination or placebo.
- Primary endpoint: Change in agitation on the Cohen-Mansfield Agitation Inventory at two weeks.
- Key secondary endpoints: Sustained agitation reduction at 12 weeks and global clinical change at two weeks and 12 weeks.
The study's drug intervention, known as T2, contained 2 mg THC and 100 mg CBD. From the start of the study through Week 1, participants received a half dose (2 mg THC and 100 mg CBD, twice daily) or a placebo. During Weeks 2–12, participants received the full intervention dose (4 mg THC and 200 mg CBD, twice daily) or a placebo.
A 12-week open-label extension phase has been completed and will also be reported at AAIC 2026. The LiBBY trial and its open-label extension are primarily funded by the NIA, part of the National Institutes of Health (NIH). The Alzheimer's Association is a funder of the open-label extension phase.
"Agitation at the end of life is distressing for both the patient with dementia and for their families," said Dr. Frank Greenway, Chief Medical Officer at Pennington Biomedical. "This study demonstrated that components of marijuana are safer, have less sedation and represent a significant improvement in the treatment of agitation."
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