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?

This trial examines how different doses of CBD, a compound from hemp, affect clopidogrel levels in the blood. Participants are divided into three groups: one takes clopidogrel alone, while the other two take clopidogrel with either a low or high dose of CBD. The study suits healthy adults familiar with hemp or cannabis, not currently on medications that might interfere, and residing within 40 miles of Spokane. The goal is to help doctors understand the safe use of CBD with clopidogrel. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking knowledge.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabidiol (CBD) is generally safe to use, but it can interact with other medications. Some studies have found that CBD can alter the levels of drugs like anti-epileptics and antidepressants in the blood, potentially affecting their efficacy.

CBD is usually well-tolerated, though some individuals might experience drowsiness or changes in blood pressure. There is also a possibility that CBD products could contain small amounts of THC, which might appear on drug tests.

This trial is in the early stages and aims to understand how CBD interacts with clopidogrel, a drug used to prevent blood clots. Currently, the trial focuses on assessing how well participants tolerate taking both CBD and clopidogrel together. Early trials like this are crucial to ensure treatments are safe for more people in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how cannabidiol (CBD), a compound derived from hemp, interacts with clopidogrel, a common blood thinner. Unlike traditional methods, which primarily focus on clopidogrel alone, this investigation looks at how CBD might alter its effects, potentially offering new insights into drug interactions. CBD is known for its anti-inflammatory properties and a relatively favorable safety profile, which could lead to improved patient outcomes if it enhances or modifies clopidogrel's efficacy or safety. By testing different CBD dosages, this trial aims to better understand the optimal combination for safe and effective use, paving the way for more personalized medicine approaches.

What evidence suggests that this trial's treatments could be effective for drug interactions?

This trial will investigate the interactions between cannabidiol (CBD) and clopidogrel, a drug that prevents blood clots. Research has shown that CBD might affect clopidogrel's efficacy by interfering with an enzyme called CYP2C19, which is necessary for converting clopidogrel into its active form. Without this conversion, clopidogrel might not prevent clots effectively, increasing risk for users. Some reports also indicate that using CBD with clopidogrel could alter heart or bleeding risks. The trial includes separate arms to study the effects of clopidogrel alone and in combination with different doses of CBD, emphasizing the importance of understanding how CBD might change clopidogrel's effects in the body. ^{4 6 7 8 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

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]

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]

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]

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]

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]

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]

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 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]

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