CBD + THC for Agitation in Dementia

(LiBBY Trial)

Recruiting at 21 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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of THC (Tetrahydrocannabinol) and CBD (Cannabidiol) can reduce agitation in people with dementia. The study compares this treatment to a placebo over 12 weeks to determine which is more effective. It seeks participants with dementia who experience significant agitation and are eligible for hospice care. Participants must agree to use only the trial's medication during the study period. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining CBD and THC might help reduce restlessness in people with dementia. One study found that a synthetic form of THC reduced restlessness in Alzheimer's patients by about 30%, suggesting it could work for similar conditions.

High amounts of CBD oil have also been noted to help manage symptoms like restlessness and anxiety in dementia patients. However, no FDA-approved drugs specifically target these symptoms in dementia, so these findings remain under investigation.

While the evidence is promising, the current trial is in an early stage. Researchers are still testing the treatment for safety and effectiveness in people. Participants in these studies help researchers understand how well the treatment is tolerated and report any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dementia?

Researchers are excited about using CBD and THC for agitation in dementia because these compounds offer a unique approach compared to typical treatments like antipsychotics and benzodiazepines. Unlike these standard drugs, which can have significant side effects, CBD and THC are derived from cannabis and may provide a more natural and potentially safer alternative. These compounds work by interacting with the body's endocannabinoid system, which is different from how most current medications function, and could lead to improved management of symptoms with fewer adverse effects. Plus, there's growing interest in cannabis-based treatments due to their potential neuroprotective and anti-inflammatory properties, which might offer additional benefits for dementia patients.

What evidence suggests that this trial's treatments could be effective for agitation in dementia?

This trial will evaluate the effects of a combination of CBD (cannabidiol) and THC (tetrahydrocannabinol) on agitation in dementia. Research has shown that a mix of CBD and THC can help reduce restlessness in people with Alzheimer's disease. For instance, one study found that synthetic cannabis, which contains these compounds, lowered restlessness by about 30% in these patients. CBD and THC might help by balancing brain chemicals, improving sleep, and boosting blood flow to the brain. Additionally, using low doses of CBD and medium doses of THC has been found to be safe and well-tolerated by patients. Overall, these findings suggest that combining CBD and THC could effectively reduce restlessness in conditions related to dementia. Participants in this trial will receive either the CBD and THC combination or a placebo. ^{1 3 6 7 8}

Who Is on the Research Team?

Paul Aisen, MD

Principal Investigator

Alzheimer's Therapeutic Research Institute

Jacobo Mintzer, MD

Principal Investigator

Ralph H. Johnson Veterans Affairs Medical Center (VAMC)

Brigid Reynolds, NP

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8313629/

Cannabinoids for Agitation in Alzheimer's Disease - PMC Cannabinoids may relieve agitation by regulating neurotransmitters, improving comorbidities and circadian rhythms, and increasing cerebral circulation.

2. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2024/10/clinical-trial-shows-synthetic-cannabis-reduces-agitation-in-alzheimers-disease

Clinical Trial Shows Synthetic Cannabis Reduces Agitation ... ... THC, reduces agitation in patients with Alzheimer's by an average of 30%. ... effects without adverse results such as delirium or seizures.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12143470/

Sativex (nabiximols) for the treatment of Agitation & ... Compared to these studies, ours applying a mixture of low dose CBD and medium dose THC appeared to be safer and better tolerated, even in a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05644262

Life's End Benefits of cannaBidiol and tetrahYdrocannabinol 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748124001830

Caring for Behavioral Symptoms of Dementia (CBD): A ... Data from our exploratory aim focused on agitation is consistent with our primary outcome data, as all five patients showed reductions in agitation symptoms ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03328676?term=olea%20europaea%20lead%20AND%20suffer&viewType=Table&checkSpell=&rank=2

The Effect of Cannabis on Dementia Related Agitation and ... In this randomized, double-blind placebo-controlled trial, 60 patients will be randomly assigned to receive either CBD-A (30:1) cannabis rich low THC oil (30% ...

7. alzheimers.org.uk alzheimers.org.uk/about-dementia/treatments/alternative-therapies/cannabis-cbd-oil-and-dementia

Cannabis, CBD oil and dementia Research does suggest that high concentrations of CBD oil could be useful for managing some of the symptoms of dementia such as agitation and anxiety. A few ...

8. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.050511

Caring for behavioral symptoms of dementia (CBD): A new ... Anxiety and agitation symptoms affect 25-70% of the dementia population, though there are no FDA-approved medications that treat the behavioral ...