Summary: Topline results from the Phase 2 LiBBY clinical trial show that a targeted oral oil formulation combining cannabidiol (CBD) and tetrahydrocannabinol (THC) produced rapid and sustained reductions in severe agitation in hospice-eligible people with advanced dementia.
The multicenter, randomized, double-blind, placebo-controlled trial evaluated a novel digestible oil formulation (designated T2) in 120 hospice-eligible dementia patients with clinically significant agitation. The formulation and dosing protocol, safety outcomes, and clinical benefits reported here summarize the primary and key secondary results presented at the Alzheimer’s Association International Conference 2026.
Key Facts
- Rapid primary outcome: By Week 2, the active THC/CBD group showed a statistically significant 6.27-point greater reduction in agitation on the Cohen-Mansfield Agitation Inventory compared with placebo, indicating fast symptom relief.
- Sustained 12-week effect: Reductions persisted through Week 12, with an 8.23-point greater decrease in agitation scores versus placebo.
- Clinician-rated global improvement: At Week 2, 83.9% of treated participants showed clinical improvement versus 30.5% on placebo; by Week 12 this was 87.2% versus 23.6%.
- Dosing (T2 oil formulation): The study drug unit contained 2 mg THC and 100 mg CBD. Participants received a titration schedule beginning with a half dose twice daily in Week 1 (total 2 mg THC / 100 mg CBD daily) and escalating to the full dose twice daily during Weeks 2–12 (total 4 mg THC / 200 mg CBD daily).
- Safety profile: Overall adverse event rates were similar between groups (46.7% treatment vs. 42.4% placebo). Over 12 weeks, 23.3% of treated participants 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.
- Unmet need: Agitation affects roughly half of people with dementia near the end of life, and more than one-third remain symptomatic despite off-label therapies such as antipsychotics, benzodiazepines, and opioids, which carry risks of severe sedation and other harms.
Source: Pennington Biomedical
The LiBBY trial (Life’s End Benefits of cannaBidiol and tetrahYdrocannabinol) was conducted by the National Institute on Aging–funded Alzheimer’s Clinical Trial Consortium and enrolled older adults with Alzheimer’s disease or other dementing illnesses who were eligible for or receiving hospice care and who experienced significant agitation. The primary endpoint measured change in agitation on the Cohen-Mansfield Agitation Inventory at two weeks; key secondary endpoints included sustained agitation reduction at 12 weeks and clinician-rated global change at two and 12 weeks.
Lead investigator Dr. Jacobo Mintzer of the Ralph H. Johnson VA Healthcare System described the findings as a “robustly positive, randomized, controlled trial” that addresses a population historically underrepresented in clinical research. Investigators noted the speed and magnitude of agitation reduction and emphasized potential benefits for patient comfort and dignity near the end of life.
Clinical and Practical Context
Agitation in severe and late-stage dementia is a common and distressing neuropsychiatric symptom, often reflecting emotional distress, pain, fear, or other unmet needs in people who no longer communicate reliably. Typical manifestations include pacing or wandering, fidgeting, repetitive movements, loud vocalizations or calling out, repetitive phrases, moaning or groaning, verbal hostility, and physical aggression such as hitting, kicking, or throwing objects. These behaviors are stressful for patients, families, and caregivers and are often managed with off-label medications that carry significant risks.
In the LiBBY trial, the THC/CBD oil produced rapid improvement in agitation with a favorable medication-related safety assessment by investigators. The study team and advocacy groups emphasize that nonpharmacological strategies—environmental adjustments, structured routines, and psychosocial interventions—remain first-line approaches, and any pharmacologic treatment should follow careful, individualized clinical judgment and shared decision-making.
Safety and Extension
The double-blind, 12-week Phase 2 study reported similar overall adverse event rates across groups and found no serious adverse events attributable to the study drug. A 12-week open-label extension has been completed and additional results will be reported at the same conference session. The LiBBY trial and its extension were primarily funded by the National Institute on Aging, with additional support for the extension from the Alzheimer’s Association.
Representative Investigator Comments
Dr. Jeff Keller of Pennington Biomedical noted that the trial proves rigorous research is possible in hospice-eligible populations and that the observed reductions in agitation can meaningfully improve palliative care. Dr. Frank Greenway, Chief Medical Officer at Pennington Biomedical, commented that components of marijuana in this formulation appeared to cause less sedation and represented an important advance in treating agitation at the end of life.
Frequently Asked Questions
Q: What dosage and route were used in the LiBBY trial?
A: The intervention was an oral digestible oil called T2. The unit dose contained 2 mg THC and 100 mg CBD. Week 1 used a half dose given twice daily (total 2 mg THC / 100 mg CBD daily), and Weeks 2–12 used the full dose twice daily (total 4 mg THC / 200 mg CBD daily).
Q: Why is it significant to run randomized trials in hospice-eligible dementia patients?
A: Historically, people in terminal stages of dementia are excluded from clinical trials because of ethical and logistical challenges. LiBBY demonstrates that carefully designed, double-blind, placebo-controlled trials can be conducted in this population to address urgent palliative care needs.
Q: How does the THC/CBD combination compare with current off-label treatments?
A: Standard off-label options—antipsychotics, benzodiazepines, and opioids—can cause severe sedation, motor impairment, and increased mortality risk and do not reliably control agitation for many patients. In this trial, the THC/CBD combination produced rapid and substantial agitation reduction with an investigator-assessed safety profile that did not link serious adverse events to the study drug.
Editorial Notes
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full by staff.
- Additional context was added by the editorial team.
About this report
Author: Ernie Ballard (Pennington Biomedical)
Source: Pennington Biomedical
Contact: Ernie Ballard – Pennington Biomedical
Original research presentation: Findings presented at the Alzheimer’s Association International Conference 2026.