Hemp Product for Drug Interactions

Overseen By Mary F Paine, RPh, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington State University

Must not be taking: Clopidogrel, others

Disqualifiers: Major illness, pregnant, cannabis naive, 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: 1

Duration: 6 days

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to determine how two different doses of cannabidiol (CBD), given as a hemp product, change the blood concentrations of the drug clopidogrel in the body. Results will be used to help design future studies and to assist healthcare providers in informing their patients about the safe use of CBD.

Will I have to stop taking my current medications?

Yes, you must stop taking any medications or supplements that could affect cannabis or clopidogrel, as the trial requires participants not to be on such medications.

Is cannabidiol (CBD) generally safe for human use?

CBD is generally considered safe for human use, but it can cause side effects like sleep disturbances, sedation, and liver issues. It may also interact with other medications, so it's important to monitor for adverse effects and consult with a healthcare provider, especially if taking other drugs. ^{1 2 3 4 5}

How does the drug Cannabidiol (CBD) differ from other treatments for drug interactions?

Cannabidiol (CBD) is unique because it can interact with many drug-metabolizing proteins, potentially affecting how other drugs are processed in the body. This makes it important to consider possible drug-drug interactions when using CBD, especially since it can both influence and be influenced by other medications. ^{1 4 6 7 8}

What data supports the effectiveness of the drug Cannabidiol (CBD) for drug interactions?

The research indicates that while CBD is widely used and has some pharmacological effects, it is primarily noted for its potential to interact with other drugs, which can lead to clinical complications. There is no direct evidence from the provided research supporting its effectiveness specifically for managing drug interactions. ^{1 4 5 6 9}

Are You a Good Fit for This Trial?

This trial is for individuals who are currently taking the drug clopidogrel. Participants should not have any health conditions that could interfere with the study or be using other medications that might affect how clopidogrel works in their body.

Inclusion Criteria

I am not on medications or supplements that affect how cannabis or clopidogrel works in my body.

Willing to abstain from consuming certain substances for the duration of the study

My genetic test shows I metabolize certain drugs normally or very quickly.

Exclusion Criteria

Any major illness

Presence of a condition that would compromise participant safety or data quality

Out-of-range clinical laboratory value that poses a health risk

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive clopidogrel alone or in combination with hemp (CBD) for pharmacokinetic analysis

6 days

1 visit (in-person) for clopidogrel alone; 1 visit (in-person) on day 6 for hemp + clopidogrel

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol

Trial Overview The study is testing how two different doses of cannabidiol (CBD), delivered as a hemp product, impact the levels and effects of clopidogrel in the bloodstream.

How Is the Trial Designed?

Group I: Arm 3: chronic hemp (240 mg CBD) + clopidogrel Experimental Treatment 2 Interventions

Participants will repeat the Arm 2 procedures using a higher dose of hemp (240 mg CBD)

Group II: Arm 2: chronic hemp (30 mg CBD) + clopidogrel Experimental Treatment 2 Interventions

Participants will self-administer a single low dose of hemp (30 mg CBD) as an oral softgel at home daily for 5 consecutive days. On day 6, participants will return to the research setting, where they will be administered a single low dose of hemp (30 mg CBD) and a single oral dose of clopidogrel (75 mg). Blood will be collected for 72 hours and urine will be collected for 24 hours.

Group III: Arm 1: clopidogrel alone Experimental Treatment 1 Intervention

Participants will be administered a single oral dose (75 mg) of clopidogrel. Blood and urine will be collected for 24 hours.

Cannabidiol is already approved in United States, European Union, Canada 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

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Washington State University

Lead Sponsor

Trials

114

Recruited

58,800+

Office of Dietary Supplements (ODS)

Collaborator

Trials

55

Recruited

54,500+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

A case study of a 58-year-old woman showed that chronic use of cannabidiol (CBD) at a low dose of 40 mg/day may inhibit the metabolism of tamoxifen, a common breast cancer treatment, potentially leading to lower levels of its active metabolite, endoxifen.

After stopping CBD, the patient's endoxifen levels increased by 18.75%, suggesting that CBD could interfere with the effectiveness of tamoxifen, highlighting the need for monitoring patients using CBD alongside chemotherapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in Tamoxifen Metabolites Endoxifen and N-desmethyltamoxifen With Chronic Administration of Low Dose Cannabidiol: A CYP3A4 and CYP2D6 Drug Interaction. Parihar, V., Rogers, A., Blain, AM., et al.[2022]

In a study of 136 patients prescribed cannabidiol (CBD) for seizure management, 80% had at least one drug-drug interaction (DDI) identified at the time of initiation, highlighting the importance of monitoring for interactions when starting CBD therapy.

The majority of identified DDIs were pharmacodynamic (71%), with clobazam being the most common interacting medication, indicating that integrated specialty pharmacists play a crucial role in managing these interactions to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription cannabidiol for seizure disorder management: Initial drug-drug interaction management by specialty pharmacists. Dial, H., Owens, W., DeClercq, J., et al.[2022]

Cannabidiol (CBD) is widely used for both medical and recreational purposes, but its pharmacological effects and potential drug interactions are not well understood, which can lead to clinical complications.

This narrative review highlights that there are several pharmacokinetic drug-drug interactions with CBD, emphasizing the need for clinicians to be aware of these interactions as CBD use becomes more common.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol and pharmacokinetics drug-drug interactions: Pharmacological toolbox. Lacroix, C., Guilhaumou, R., Micallef, J., et al.[2023]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

Serious adverse effects (SAEs) from cannabidiol (CBD) are rare, with most being mild to moderate, and primarily include elevated liver enzymes, sedation, and respiratory infections, particularly when used with certain medications.

Elevated liver enzymes were specifically linked to the use of valproate, while sedation and lethargy were associated with clobazam, indicating that patients, especially those with epilepsy, should be closely monitored for potential drug-drug interactions when using CBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. Dos Santos, RG., Guimarães, FS., Crippa, JAS., et al.[2022]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

A study identified 403 drugs that can interact with cannabidiol (CBD), with 53 of these showing reported interactions, indicating a significant potential for CBD to affect the metabolism of commonly prescribed medications.

Among the most frequently prescribed drugs in Germany and the USA, a high percentage (67% and 68%, respectively) are substrates of drug-metabolizing proteins, highlighting the urgent need for further research on CBD-drug interactions to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol's impact on drug-metabolization. Stöllberger, C., Finsterer, J.[2023]

CANN-DIR™ is a new free web-based platform designed to help users identify potential drug-drug interactions involving cannabinoids like THC and CBD, based on FDA-approved information.

This platform not only provides quick access to interaction data but also allows users to print results in ten different languages, facilitating better communication between patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CANNabinoid Drug Interaction Review (CANN-DIR™). Kocis, PT., Wadrose, S., Wakefield, RL., et al.[2023]

Citations

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

Reduction in Tamoxifen Metabolites Endoxifen and N-desmethyltamoxifen With Chronic Administration of Low Dose Cannabidiol: A CYP3A4 and CYP2D6 Drug Interaction. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Prescription cannabidiol for seizure disorder management: Initial drug-drug interaction management by specialty pharmacists. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Cannabidiol and pharmacokinetics drug-drug interactions: Pharmacological toolbox. [2023]

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

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. [2022]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cannabidiol's impact on drug-metabolization. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

CANNabinoid Drug Interaction Review (CANN-DIR™). [2023]