THC and CBD Combination Reduces Agitation in Late-Stage Alzheimer’s Patients

Phase 2 LiBBY Trial Data Demonstrates THC and CBD Efficacy

The LiBBY Trial Results and Symptom Improvement

For as many as half of those who develop Alzheimer’s, agitation symptoms—such as pacing, emotional distress, or verbal and physical aggression—become more common in later stages of the disease. This agitation often results in increased rates of anxiety and depression for caregivers. At the Alzheimer’s Association International Conference in London, investigators shared findings from the Phase 2 LiBBY trial, which tested a novel formula of 2 mg of THC and 100 mg of CBD dissolved in digestible oil, administered twice daily.

According to Being Patient, the study recruited 120 participants with dementia and agitation who were either eligible for or already receiving hospice care. In this double-blind trial, half of the participants were randomly assigned to a placebo group, while the other half received the THC/CBD treatment. Neither the researchers conducting the study nor the participants knew who received the actual medication.

The results indicated a rapid response: after two weeks, patients receiving the THC/CBD combination showed a 6.27-point greater reduction on the Cohen-Mansfield Agitation Inventory (CMAI)—a 203-point scale of agitation symptoms—compared to the placebo group. In the treatment arm, more than 80 percent of participants showed improvement compared to 30 percent in the placebo arm. By the 12-week mark, the difference in the CMAI score grew to 8.23 points, with a total of 87 percent of participants in the treatment group experiencing improvement.

Dr. Jacobo Mintzer, a psychiatrist at the Ralph H. Johnson VA Healthcare System who presented the data, expressed surprise at the efficacy of the intervention. “I haven’t seen one [treatment] study in my life, no matter about what, that has an 80 percent response at two weeks,” said Mintzer. He noted that in the 12-week open-label portion of the study, where participants were knowingly given the treatment, they continued to improve.

Safety Profiles and Clinical Methodology

The trial design allowed participants to remain on their existing medications, as researchers often exclude participants from trials if they are taking many medications because it might drown out the effects of a medication. Regarding safety, at 12 weeks, 23.3 percent of participants who received THC/CBD developed severe adverse events compared to 11.9 percent in the placebo group. However, researchers determined that these effects were unrelated to the medication, explaining that these severe events referred to patient deaths and that the underlying causes were unrelated to the treatment. In the 12-week open-label portion of the study, there was no difference in deaths.

For more on this story, see THC-CBD Combination Reduces Agitation in Late-Stage Dementia Patients.

External experts have expressed interest in the potential for these findings to fill a gap in care. Dr. Jerry Gurwitz, a geriatrician at UMass Chan Medical School, who was not involved in the study, told Being Patient: I think the findings are really intriguing. Dr. Jacobo Mintzer, who presented the study, stated: “We made a commitment to try to find a drug or treatment that will alleviate the symptoms and take away the agitation and the despair of these patients.” The researchers have not yet announced a Phase 3 trial.

Healthcare Providers Utilize Multi-Layered Strategies for Agitation Management

Standard Care Strategies for Agitation

While the LiBBY trial explores new pharmacological avenues, current clinical protocols for managing agitation remain focused on multi-layered strategies. Healthcare providers note that treatment depends on the context, the cause, and the severity of the agitation. When agitation is a symptom of a chronic condition, providers work to build a treatment plan that may include medication and psychotherapy.

General strategies for managing agitation include:

• De-escalation: A provider speaks calmly with the agitated person, ensuring their concerns are addressed. This can sometimes be all that is necessary to manage the situation.
• Seclusion: If de-escalation is not working, a provider may ask the person if they would like to go into a quiet room to help resolve the agitation.
• Medication: If other methods do not help, providers may use medications that cause sedation, such as second-generation antipsychotic medications or benzodiazepines.
• Restraints: Physical restraints are considered an absolute last resort, used only if other methods have failed and the person is at risk of self-harm or harming others.

Caregivers Develop Action Plans to Minimize Conflict

For mild episodes, individuals may find relief by minimizing conflict, relaxing in a quiet room, practicing meditation, or engaging in physical activity. Because agitation often stems from a feeling of loss of control, experts recommend that caregivers develop an action plan in collaboration with a healthcare team. Readers concerned about agitation symptoms are encouraged to consult a qualified healthcare professional to discuss the best strategies for their specific situation, as the sooner you get help, the better.

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