Cannabidiol Solution for Alzheimer's Disease

(CBD Trial)

Overseen By Emily H Kim, BS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mclean Hospital

Must not be taking: Cannabinoids, CYP3A4 inhibitors, CYP2C19 inhibitors, Antiepileptics

Disqualifiers: Bipolar, Schizophrenia, Depression, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special solution primarily composed of CBD with a small amount of THC, administered under the tongue, to help reduce anxiety and agitation in individuals with mild cognitive impairment or mild to moderate Alzheimer's Disease. Researchers aim to determine if this CBD solution can enhance daily life for those experiencing these symptoms. The trial is open to individuals with mild cognitive impairment or Alzheimer's who experience significant anxiety and have a caregiver for support. Participants should not regularly use cannabinoid products and must not have serious medical conditions that could interfere with the trial. As an Early Phase 1 trial, this study focuses on understanding how this new treatment works in people, offering participants the opportunity to be among the first to try it.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications, specifically strong inhibitors or inducers of CYP3A4 and CYP2C19, or anti-epileptic drugs. If you are on these medications, you may need to stop them to participate.

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

Research has shown that a sublingual solution with high CBD and low THC is generally well-tolerated by people with Alzheimer's disease. Studies have found that this treatment can safely help manage anxiety and agitation in patients. One study found that CBD-rich oil was effective and safe for treating behavioral and mood-related symptoms in Alzheimer's patients, and it also helped reduce stress for caregivers.

While there is still more to learn, early findings suggest that most patients handle this treatment well, with few serious side effects. Since this trial is in an early phase, the main goal is to understand its safety and how well people tolerate it. Researchers are closely monitoring for any side effects to ensure safety for those with mild cognitive impairment or mild to moderate Alzheimer's disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for Alzheimer's disease, which often focus on managing symptoms through medications like cholinesterase inhibitors and memantine, this new approach uses a high CBD/low THC sublingual solution. Researchers are excited about this treatment because cannabidiol (CBD) acts on the endocannabinoid system, which is thought to have neuroprotective effects that could potentially slow down the progression of Alzheimer's. Additionally, the sublingual delivery method allows for rapid absorption, potentially leading to quicker therapeutic effects compared to traditional oral medications. This innovative approach offers a fresh perspective on tackling Alzheimer's disease beyond just symptom management.

What evidence suggests that this high CBD/low THC solution might be an effective treatment for Alzheimer's Disease?

Research has shown that cannabidiol (CBD) may help reduce symptoms of Alzheimer's disease, such as anxiety and restlessness. Studies suggest that small amounts of cannabinoids, like CBD, might improve these symptoms. CBD helps calm anxiety, which could benefit people with Alzheimer's. It also seems to influence genes related to the disease, possibly providing more relief. Overall, early findings are promising, but more research is needed to confirm these effects. Participants in this trial will receive a high CBD, low THC sublingual solution to further investigate these potential benefits. ^{1 2 6 7 8}

Who Is on the Research Team?

Ipsit V Vahia, MD

Principal Investigator

Mclean Hospital

Staci Gruber, PhD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

This trial is for older adults aged 60-90 with mild to moderate Alzheimer's Dementia, experiencing significant anxiety. Participants must have a caregiver, an MMSE score of 15-24, and be fluent in English. Those with recent substance abuse, certain medication use, severe allergies (like coconut), or major psychiatric disorders other than Alzheimer's are excluded.

Inclusion Criteria

I have been diagnosed with Alzheimer's based on specific criteria.

You have a high level of anxiety, as determined by a specific test score.

I am between 60 and 90 years old.

Exclusion Criteria

I have a seizure disorder.

You have been diagnosed with bipolar disorder, schizophrenia, or schizoaffective disorder at any time in your life.

Current inpatient hospitalization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a high CBD/low THC sublingual solution for the treatment of anxiety and agitation

8 weeks

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Optional Follow-up

Exploratory investigation into the stability of anxiety and caregiver burden reduction

12 months

Visits at months 3, 6, 9, and 12

What Are the Treatments Tested in This Trial?

Interventions

• high CBD/low THC sublingual solution

Trial Overview The study tests a high CBD/low THC sublingual solution over eight weeks to see if it reduces anxiety and agitation in Alzheimer's patients. It’s an open label trial meaning everyone knows they're getting the actual treatment without any placebo comparison.

How Is the Trial Designed?

Group I: All subjects Experimental Treatment 1 Intervention

This arm will include all subjects, individuals will administer a high CBD, low THC full spectrum sublingual solution twice daily on a variable dosing schedule.

high CBD/low THC sublingual solution is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dronabinol (synthetic THC) for:

• Nausea and vomiting associated with cancer chemotherapy
• Loss of appetite in patients with HIV/AIDS
• Agitation in Alzheimer's disease (off-label)

Approved in Canada as Nabilone (synthetic THC) for:

• Nausea and vomiting associated with cancer chemotherapy

Approved in European Union as Cannabidiol (CBD) for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Spier Family Foundation

Collaborator

Trials

2

Recruited

70+

Published Research Related to This Trial

In a study involving female APPxPS1 mice, daily treatment with 20 mg/kg of cannabidiol (CBD) for 8 months improved spatial learning and memory, as evidenced by reduced latencies in finding food rewards compared to untreated controls.

CBD treatment did not affect anxiety-like behaviors but did increase locomotion in the APPxPS1 mice, suggesting that CBD may have potential as a preventive therapy for cognitive decline in female Alzheimer's disease models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer's disease mouse model. Chesworth, R., Cheng, D., Staub, C., et al.[2022]

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]

High oral doses of cannabidiol (CBD), specifically 300-400 mg per day, have shown efficacy in reducing anxiety and providing anti-addiction effects without increasing adverse effects, based on a review of interventional studies.

Therapeutic benefits of CBD are less clear at lower doses (below 300 mg/day), indicating a need for larger clinical trials to better understand the potential effects of low-dose CBD products, which are widely available as nutraceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. Arnold, JC., McCartney, D., Suraev, A., et al.[2023]

PTL101, an oral formulation of highly purified CBD, was found to be safe and well-tolerated in healthy volunteers, showing a significant increase in CBD absorption compared to the Sativex oromucosal spray.

The 10 mg dose of PTL101 demonstrated 134% bioavailability relative to the reference spray, indicating that it delivers CBD more effectively, which could make it a promising option for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. Atsmon, J., Heffetz, D., Deutsch, L., et al.[2022]

A 5.0% cannabidiol (CBD) gel showed a significant reduction in neurodegeneration in the entorhinal cortex, with a 48.8% decrease in neurodegeneration, indicating potential neuroprotective effects against alcohol-induced damage.

Transdermal delivery of CBD was found to be as effective as intraperitoneal injection in reducing neurodegeneration, with a 56.1% reduction in neurodegeneration from the gel compared to 50.6% from the injection, suggesting that CBD can be effectively administered through the skin for treating alcohol-related neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder. Liput, DJ., Hammell, DC., Stinchcomb, AL., et al.[2021]

In a study using an animal model, cannabidiol (CBD) significantly improved memory in rats with cognitive impairment caused by iron overload, indicating its potential as a treatment for cognitive decline associated with neurodegenerative disorders.

Both acute (single high dose) and chronic (daily doses for 14 days) administration of CBD enhanced recognition memory in impaired rats, while having no effect on memory in healthy control rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders. Fagherazzi, EV., Garcia, VA., Maurmann, N., et al.[2021]

In a study involving 93 patients with Dravet and Lennox-Gastaut syndromes, purified cannabidiol (CBD) demonstrated a 40.2% reduction in seizure frequency after 3 months of treatment, indicating its potential efficacy for patients with highly refractory epilepsy.

The safety profile of CBD showed that 31.2% of patients dropped out due to lack of efficacy or adverse events, with common side effects including somnolence and diarrhea, suggesting that while CBD can improve seizure control, it may also lead to tolerability issues in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome. Iannone, LF., Arena, G., Battaglia, D., et al.[2021]

Cannabidiol (CBD) shows promise in treating Alzheimer's disease by reducing cognitive deficits and protecting neurons from Aβ-induced toxicity, as demonstrated in both in vitro and in vivo studies.

CBD works by modulating microglial activity, promoting the release of neurotrophic factors, and regulating inflammatory genes, suggesting it could be a valuable addition to nutritional guidelines for Alzheimer's disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration. Chen, L., Sun, Y., Li, J., et al.[2023]

Cannabidiol (CBD) shows promise as a potential treatment for Alzheimer's disease (AD) by reducing neuroinflammation, promoting neurogenesis, and reversing cognitive deficits in animal models, indicating its neuroprotective properties.

Combination therapies of CBD with Δ9-tetrahydrocannabinol (THC) may enhance therapeutic benefits while mitigating THC's psychoactive effects, suggesting a multifaceted approach to AD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease. Watt, G., Karl, T.[2020]

The endocannabinoid system is significantly impacted in Alzheimer's disease (AD), and phytocannabinoids like CBD and THC show promise in reversing cognitive deficits and improving cognition in animal models of AD.

Using a multi-cannabinoid approach, such as whole plant extracts or specific CBD:THC combinations, may enhance therapeutic effects compared to using individual cannabinoid isolates, but more clinical studies are needed to optimize treatment strategies and assess side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease. Coles, M., Steiner-Lim, GZ., Karl, T.[2022]

This clinical trial will assess the effects of daily CBD treatment over 12 weeks in 60 participants with early-stage dementia, focusing on neurobiological, behavioral, and psychological outcomes.

The study aims to provide insights into whether CBD can improve quality of life and treatment outcomes for individuals with dementia, marking one of the first investigations into isolated CBD's potential benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol as a Treatment for Neurobiological, Behavioral, and Psychological Symptoms in Early-Stage Dementia: A Double-Blind, Placebo-Controlled Clinical Trial Protocol. Bartschi, JG., Greenwood, LM., Montgomery, A., et al.[2023]

Citations

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A randomized clinical trial of low-dose cannabis extract ... Preclinical and clinical evidence suggest that low-dose cannabinoids could ameliorate Alzheimer's disease (AD) signs and symptoms.

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The Main Therapeutic Applications of Cannabidiol (CBD) and ... A substantial part of the text deals with the main effects of CBD on aging, including Alzheimer's disease and related underlying mechanisms.

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Cannabidiol and Alzheimer Disease - PubMed Central - NIH Cannabidiol improves several Alzheimer's‐related aspects and regulates disease‐associated genes. Literature review and Over‐Representation Analysis of 64 genes ...

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Treatment of Neuropsychiatric Symptoms in Alzheimer's ... This study shows that CBD-rich oil is an effective and safe therapy for treating NPS in AD patients, while also reducing the caregivers' distress.

7. ctv.veeva.com ctv.veeva.com/study/cannabidiol-solution-for-the-treatment-of-behavioral-symptoms-in-older-adults-with-alzheimers-demen

Cannabidiol Solution for the Treatment of Behavioral ... This is an open label, eight week, clinical trial of a proprietary high CBD/low THC sublingual solution for the treatment of clinically ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748121001330

NR-8 Caring for Behavioral Symptoms of Dementia (CBD) ... The present open-label clinical trial seeks to address this gap in knowledge by assessing the efficacy and tolerability of a high-CBD/low-THC sublingual ...