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NCT04392011

EARLY_PHASE1

Assessing the Pharmacokinetics and Drug Interaction Liability of Kratom, an Opioid-like Natural Product

Sponsor: Washington State University

View on ClinicalTrials.gov

Summary

Kratom is a botanical natural product that has opioid-like effects. Kratom is commonly used to self-treat withdrawal symptoms associated with opioid addiction, as well as pain. Kratom products include pills, extracts, and powders, most of which contain two primary psychoactive constituents: mitragynine and 7-hydroxymitragynine. Preliminary data from the investigator's laboratory has shown that these two constituents and extracts made from commercially available kratom products are strong inhibitors of the drug metabolizing enzymes cytochrome P450 (CYP) 2D6 and CYP3A4. These enzymes are responsible for metabolizing more than 50% of marketed drugs, including several opioids, benzodiazepines, and antidepressants. Thus, co-consumption of kratom products with drugs metabolized by CYP2D6 and CYP3A4 could increase the risk of serious adverse effects. The effects of a well-characterized kratom product on CYP2D6 and CYP3A4 activity will be assessed in healthy volunteers using a 'cocktail' approach consisting of the validated probe drugs dextromethorphan and midazolam. Results will (1) provide useful information regarding risks associated with co-consuming kratom with opioids and other CYP2D6 and CYP3A4 drug substrates and (2) inform the design of future kratom-drug interactions studies.

Key Details

Gender

All

Age Range

18 Years - 55 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2019-10-09

Completion Date

2021-08-31

Last Updated

2026-10-19

Healthy Volunteers

Yes

Conditions

Interaction Drug Food

Interventions

DRUG

Midazolam HCl

Oral syrup, 2 mg/mL

DRUG

Dextromethorphan HBr

Oral liquid capsules, 15 mg

DIETARY_SUPPLEMENT

Kratom

Kratom (Moon Kratom Yellow Indonesian, lot 51) is supplied as a dry leaf powder in clear plastic bags, each weighing 5 kg. Two g of kratom dry leaf powder will be stirred into 240 mL of hot water to make a tea. The tea will be cooled to 50 degrees Celsius before administration. Subjects will drink the tea within 10 minutes of administration.

Inclusion Criteria: * Not taking any medications (prescription and non-prescription) or dietary/herbal supplements known to alter the pharmacokinetics of either study drug or kratom constituents * Willing to abstain from consuming dietary/herbal supplements, including kratom, and citrus juices for several weeks * Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and morning of the first day of a study arm * Willing to abstain from consuming any alcoholic beverages for one day prior to any study day, during the 14-hour inpatient days, and for the 5 and/or 1 outpatient visit(s) following 14-hour visit * Willing to use an acceptable method of contraception that does not include oral contraceptive pills or patches (such as abstinence, copper IUD, condom) * Have the time to participate * Are non-naïve kratom users (intermittent users who are not trying to quit but willing to abstain for several weeks) * Carry a CYP2D6 genotype designated as having an intermediate, extensive, or ultra-extensive metabolizer phenotype * Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for the subject to comply with the requirements of the study Exclusion Criteria: * Men and women under the age of 18 or over the age of 55 * Unwilling to abstain from kratom for several weeks * Any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, or HIV/AIDS * History of anemia or any other significant hematologic disorder * History of drug or alcohol addiction or major psychiatric illness * A need for chronic opioid analgesics * Use of opioid analgesics 3 weeks prior to initiation of the study * An imminent likely need for opioid analgesics (e.g., planned dental or surgical procedure) * Female and pregnant or nursing * Have a history of allergy to dextromethorphan, midazolam, or related drugs * Have a history of intolerance or allergy to kratom or opioids * Taking concomitant medications, both prescription and non-prescription (including dietary supplements/herbal products), known to alter the pharmacokinetics of either study drug or kratom constituents * Carry a CYP2D6 genotype designated as having a poor metabolizer phenotype * Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data

Locations (1)

Washington State University College of Pharmacy and Pharmaceutical Sciences

Spokane, Washington, United States