CBD + THC for Agitation in Dementia

(LiBBY Trial)

Recruiting at 20 trial locations

Overseen By ATRI Recruitment Unit

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Cannabinoids

Disqualifiers: Cannabinoid allergy, Investigational drugs, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter randomized double-blind placebo-controlled Phase 2 study of an oral combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) compared to placebo over 12 weeks. This study is designed to test the hypothesis that treatment with an oral combination of THC/CBD will reduce agitation hospice care-eligible patients with agitation and dementia as measured by the Cohen Mansfield Agitation Inventory (CMAI) when compared to placebo at 2 weeks. This study will enroll approximately 150 participants of any gender at least 40 years of age who are hospice care-eligible with agitation and dementia (HAD). Participants will be randomized (50:50) to either active study drug (T2:C100) or placebo. The double-blind period of this study is 12 weeks. A 12 week optional open-label extension will be offered to participants who complete the double-blind period.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not use any cannabinoids (like marijuana) during the first 12 weeks of the study.

What data supports the effectiveness of the drug for agitation in dementia?

Research suggests that cannabinoids, including THC and CBD, may help reduce agitation in dementia patients. Studies have shown that these compounds can be effective and safe, with fewer side effects compared to traditional medications used for dementia-related behaviors. ^{1 2 3 4 5}

Is the combination of CBD and THC safe for treating agitation in dementia?

Studies suggest that using CBD and THC together is generally safe for older people with dementia-related agitation, with few short-term side effects. However, more research is needed to fully understand their safety and effectiveness. ^{2 3 4 6 7}

How is the drug CBD + THC unique for treating agitation in dementia?

The CBD + THC drug is unique for treating agitation in dementia because it targets the endocannabinoid system, which may help reduce neuroinflammation and enhance brain health, offering a potentially safer alternative to traditional medications that often have more side effects. ^{2 3 5 6 7}

Research Team

Brigid Reynolds, NP

Principal Investigator

Georgetown University

Paul Aisen, MD

Principal Investigator

Alzheimer's Therapeutic Research Institute

Jacobo Mintzer, MD

Principal Investigator

Ralph H. Johnson Veterans Affairs Medical Center (VAMC)

Eligibility Criteria

This trial is for hospice care-eligible patients aged 40 or older with dementia and significant agitation. They must not use other cannabinoids during the study, be able to take liquid medication, have a caregiver to help with the study requirements, and meet specific clinical criteria.

Inclusion Criteria

As assessed by investigator, participant is likely to be able to comply with the protocol for a minimum of 2 weeks

My condition is at stage 6d of the FAST scale.

You are showing signs of strong restlessness or nervousness during the screening test.

Exclusion Criteria

I am not allergic to cannabinoids or oils like coconut or sesame oil.

Treatment with another investigational drug or other investigational intervention within the previous 30 days or five half-lives of the investigational product, whichever is longer

Any condition, which in the opinion of the site PI, Data and Coordinating Center, regulatory sponsor, or Project Lead/Protocol PI, makes the participant unsuitable for inclusion

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an oral combination of THC/CBD or placebo over a 12-week double-blind period

12 weeks

Visits at Baseline, Day 7, Day 14, Week 4, Week 8, and Week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with THC/CBD for an additional 12 weeks

12 weeks

Treatment Details

Interventions

• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC)

Trial Overview The trial tests an oral mix of THC/CBD against a placebo over 12 weeks to see if it reduces agitation in dementia patients. Participants are randomly assigned to either the drug or placebo group in equal numbers.

Participant Groups

Group I: T2:C100 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Cannabidiol (CBD) is already approved in United States, European Union for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Alzheimer's Clinical Trials Consortium

Collaborator

Trials

5

Recruited

2,800+

Alzheimer's Therapeutic Research Institute

Collaborator

Trials

18

Recruited

58,400+

Findings from Research

In a study involving 10 dementia patients, THC was found to be rapidly absorbed with dose-linear pharmacokinetics, showing significant interindividual variability in how patients responded to the drug.

Only a few adverse events were related to THC, indicating that it may be safe for use in dementia patients, although further research is needed to explore the effects and efficacy of higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. Ahmed, AI., van den Elsen, GA., Colbers, A., et al.[2022]

Cannabinoids, particularly those containing both THC and CBD, have shown neuroprotective effects and can safely reduce agitation in older adults with dementia, based on previous studies.

Unlike traditional dementia medications that often have significant side effects, cannabinoids are generally well tolerated with few short-term adverse effects, highlighting their potential as a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Cannabis for Agitation in Patients With Dementia. Mueller, A., Fixen, DR.[2021]

In a study of 30 Alzheimer's disease patients aged 65-90, the administration of a THC:CBD cannabis extract for 12 weeks significantly reduced symptoms such as agitation, irritability, and sleep disturbances, improving caregiver distress.

The study also found that 45% of patients showed a significant decrease in cognitive impairment, indicating potential efficacy of cannabis extracts in managing severe symptoms of Alzheimer's disease, despite limitations like the small sample size and lack of a control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. Palmieri, B., Vadalà, M.[2023]

This ongoing clinical trial is investigating the safety and efficacy of dronabinol, a synthetic form of THC, as a treatment for agitation in Alzheimer's dementia, involving 80 participants over three weeks.

Preliminary data from 44 participants indicate a sample with significant cognitive impairment and agitation, suggesting that dronabinol could potentially address a critical gap in treatment options for Agit-AD, as there are currently no FDA-approved medications for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD). Cohen, LM., Ash, E., Outen, JD., et al.[2022]

A randomized, double-blind, placebo-controlled trial is investigating the safety and efficacy of nabiximols (a cannabis-based oral spray) for treating chronic pain and agitation in nursing home residents with severe dementia, where up to 80% experience chronic pain and 97% have fluctuating neuropsychiatric symptoms.

The study aims to assess pain and agitation using validated scales and evaluate quality of life, potentially offering a safer alternative to neuroleptics, which can double the risk of death in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD): Clinical trial protocol. Scuteri, D., Guida, F., Boccella, S., et al.[2022]

In a study involving 96 male rats (48 WKY rats with depressive-like behaviors and 48 control Wistar rats), cannabidiol (CBD) demonstrated a significant prohedonic effect at a dose of 30 mg/kg, suggesting its potential as an antidepressant.

CBD also improved motivation and exploration behaviors in WKY rats at doses of 15 mg/kg and 45 mg/kg, indicating its possible efficacy in treating conditions characterized by low motivation and anhedonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prohedonic Effect of Cannabidiol in a Rat Model of Depression. Shoval, G., Shbiro, L., Hershkovitz, L., et al.[2022]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Use of Cannabis for Agitation in Patients With Dementia. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD). [2022]

5. France pubmed.ncbi.nlm.nih.gov

NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD): Clinical trial protocol. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Prohedonic Effect of Cannabidiol in a Rat Model of Depression. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. [2020]