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

Trial Summary

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.

What data supports the effectiveness of the drug for Alzheimer's disease?

Research shows that cannabidiol (CBD) has neuroprotective, anti-inflammatory, and antioxidant properties, which can help reduce brain inflammation and promote brain cell growth. In animal studies, CBD has been shown to improve memory and cognitive function, suggesting it may be beneficial for Alzheimer's disease. ^{1 2 3 4 5}

Is Cannabidiol Solution safe for human use?

Cannabidiol (CBD) has been shown to be generally safe in humans, with studies indicating that low to moderate doses do not significantly increase adverse effects. Common side effects include sleepiness and diarrhea, but these are not dose-related. CBD has been used safely in various conditions, including epilepsy and Alzheimer's disease, with no major safety concerns reported. ^{1 6 7 8 9}

How is the Cannabidiol Solution for Alzheimer's Disease different from other drugs?

The Cannabidiol Solution for Alzheimer's Disease is unique because it uses a high CBD/low THC formulation, which is non-psychoactive and has shown potential to reduce inflammation, protect nerve cells, and improve memory in animal models. Unlike current treatments that do not stop disease progression, this solution may offer a novel approach by targeting multiple aspects of Alzheimer's pathology. ^{3 4 9 10 11}

What is the purpose of this trial?

This is an open label, eight week, clinical trial of a proprietary high CBD/low THC sublingual solution for the treatment of clinically significant anxiety and agitation in individuals with mild cognitive impairment (MCI) or mild to moderate Alzheimer's Disease (AD).

Research Team

Ipsit V Vahia, MD

Principal Investigator

Mclean Hospital

Staci Gruber, PhD

Principal Investigator

Mclean Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

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

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

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease. [2020]

5. United States 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. [2023]

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

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration. [2023]

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

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. [2023]

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

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer's disease mouse model. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders. [2021]