THC/CBD Combination Cuts Agitation in Hospice-Eligible Dementia: LiBBY Trial

Topline results from the LiBBY trial (Life's End Benefits of cannaBidiol and tetrahYdrocannabinol; NCT05644262) were presented in the Developing Topics session at the 2026 Alzheimer's Association International Conference (AAIC) in London. The trial evaluated T2:C100, an oral rapid-acting formulation containing 2 mg THC and 100 mg CBD, in patients with clinically significant agitation who were hospice-eligible or receiving end-of-life dementia care, a population largely excluded from prior dementia trials.¹

"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," co-lead investigator Jacobo Mintzer, MD, of the Ralph H. Johnson VA Healthcare System and Medical University of South Carolina, said in a statement.¹

Co-lead investigator Brigid Reynolds, MSN, APRN, ANP-BC, of Georgetown University, added, "Agitation affects many people with late-stage dementia, causing symptoms such as restlessness, aggression, and emotional distress that can profoundly impact patients and their caregivers. Current treatment options are limited and often carry significant side effects, underscoring the need for safer, more effective therapies."¹

Study design and population

The multicenter, randomized, double-blind, parallel-group study enrolled 120 participants (mean age, 80 years; 55% female; 84% Caucasian or White; 45% Hispanic or Latino) across 10 US sites, with visits conducted in participants' homes or places of residence. Following screening, 61 participants were randomized to T2:C100 and 59 to placebo; dosing began at a half dose during week 1 and escalated to the full twice-daily dose from week 2 through week 12, followed by an optional open-label extension to week 24.

To qualify, participants needed to meet DSM-5 criteria for major neurocognitive disorder with an agitation subscale score of 4 or higher, and either be enrolled in hospice care or meet advanced-dementia severity thresholds (FAST stage 6D or higher, or ADEPT score of 12 or higher). Recent cannabinoid use and known hypersensitivity to cannabinoids or sesame oil were exclusionary.

Retention was notably high given the population's advanced illness: 46 of 61 (75%) T2:C100 participants and 54 of 59 (92%) placebo participants completed the double-blind phase, with most discontinuations in the active arm attributable to death or study partner withdrawal rather than adverse events.

Primary and key secondary endpoints

The primary endpoint, change in agitation on the Cohen-Mansfield Agitation Inventory (CMAI) at 2 weeks, favored T2:C100, with a mean 6.27-point greater reduction in agitation scores versus placebo.³ The treatment effect was sustained through week 12, with a mean area-under-curve contrast between arms of -8.23 (95% CI, -11.6 to -4.86; P < .0001) and statistically significant separation at every assessed timepoint (week 1, P = .0111; week 2, P = .0003; week 4, P < .0001; week 8, P = .0002; week 12, P < .0001).¹

On the key secondary Clinical Global Impression of Change in Behavior (CGIC-B), 83.9% of T2:C100 participants showed improvement at 2 weeks versus 30.5% of placebo participants (P < .0001), and 87.2% versus 23.6% at 12 weeks (P < .0001). Investigators reported that close to 90% of treated participants showed overall improvement by week 12, a response rate researchers described as unusually high for a dementia trial. Results were reported as consistent across sensitivity analyses and prespecified subgroups.^1,2

Safety and mortality findings

Overall treatment-emergent adverse event (TEAE) rates were similar between arms through week 12 (46.7% T2:C100 vs 42.4% placebo), with infections/infestations and nervous system disorders the most common categories; serious AEs were more frequent with T2:C100 (23.3% vs 11.9%), driven largely by a higher rate of serious infections (11.7% vs 1.7%).²

Deaths occurred in 8 of 61 T2:C100 participants (13.1%) versus 3 of 59 placebo participants (5.1%) through week 12 (difference, 8%; 95% CI, 3.8%-19.6%); reported causes included sepsis, pulmonary embolism, dementia, Creutzfeldt-Jakob disease, malnutrition, and urinary tract infection in the T2:C100 arm, and respiratory distress and dementia in the placebo arm. Investigators reported that a review of individual cases found no consistent pattern in cause of death and that none were adjudicated as related to the investigational product.

Clinical context and caveats

LiBBY's primary and secondary endpoints contrast with prior cannabinoid trials in this space. A 2019 randomized, placebo-controlled crossover trial of nabilone, a synthetic THC analog, showed benefit on the CMAI but only a trend on global outcome measures.⁴ The mechanistic rationale for combining THC and CBD draws on differing receptor pharmacology: THC acts directly at CB1 and CB2 cannabinoid receptors, while CBD is a non-psychoactive agonist at the serotonin 5-HT1A receptor, an interaction first characterized in vitro nearly two decades ago.⁵

Investigators cautioned that findings apply specifically to the purified T2:C100 compound at the dose and delivery system studied, not to commercially available cannabis products. "People should not assume that products available at dispensaries or online are equivalent to what was studied in this trial," Reynolds said. "The medication used in this research was carefully formulated, manufactured, and administered under close medical supervision. Over-the-counter or commercially available THC and CBD products may vary widely in their composition, quality, and dosing, making them potentially ineffective or even harmful."¹ An open-label extension of the trial has been completed and was also presented at AAIC 2026, with early data suggesting continued improvement among participants who began active treatment during the double-blind phase.

Click here for more AAIC 2026 coverage.

REFERENCES
1. Combination of THC and CBD significantly reduced agitation in people with late-stage dementia. News release. Georgetown University Medical Center. July 14, 2026. Accessed July 22, 2026. https://www.eurekalert.org/news-releases/1135740
2. Mintzer J, Reynolds B. The LiBBY Trial: Life's End Benefits of cannaBidiol and tetrahYdrocannabinol Trial, Double-Blind Phase Topline Results. Presented at: Alzheimer's Association International Conference; July 12-15, 2026; London, England. ClinicalTrials.gov identifier: NCT05644262. https://clinicaltrials.gov/study/NCT05644262
3. THC/CBD Combination Eases Agitation in Dementia: AAIC 2026. Alzheimer's Association International Conference. July 14, 2026. Accessed July 22, 2026. https://aaic.alz.org/releases-2026/libby-trial-thc-cbd-agitation-late-stage-dementia.asp
4. Herrmann N, Ruthirakuhan M, Gallagher D, et al. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2019;27(11):1161-1173. doi:10.1016/j.jagp.2019.05.002
5. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037-1043. doi:10.1007/s11064-005-6978-1