Kratom-Oxycodone Interaction Study for Herbal Interaction

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Washington State University

Must not be taking: Opioids, Amphetamines, Benzodiazepines, others

Disqualifiers: Chronic illness, Substance abuse, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is studying how kratom tea affects the body's processing and response to the pain medication oxycodone. Healthy adults will take kratom tea and oxycodone in different combinations. Researchers aim to see if kratom changes how oxycodone is broken down and its effects on the body. Kratom is a herb with a long history of traditional use in Southeast Asia, known for its stimulant properties at low doses and effects similar to opioids at higher doses.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications or supplements that affect how kratom or oxycodone are processed by the body. The trial requires participants to not take such medications or supplements.

What data supports the effectiveness of the drug Kratom when used with Oxycodone?

Kratom is used for its opioid-like effects to help manage opioid withdrawal and pain, but there is limited clinical research on its interactions with other drugs like Oxycodone. Some studies suggest Kratom can affect how the body processes certain drugs, potentially leading to interactions, but more research is needed to understand its effectiveness and safety. ^{1 2 3 4 5}

Is the combination of kratom and oxycodone safe for humans?

Kratom, a natural product with opioid-like effects, has been associated with potential safety concerns, especially when used with other drugs. It can interact with certain enzymes in the body, potentially leading to serious drug interactions. Reports have linked kratom to adverse reactions, including toxicity and seizures, and it has been involved in overdose deaths when combined with other substances. ^{1 2 3 4 6}

How is the Kratom-Oxycodone drug unique compared to other drugs for opioid withdrawal?

The Kratom-Oxycodone drug is unique because it combines kratom, a natural product with opioid-like effects, with oxycodone, a prescription opioid, to potentially manage opioid withdrawal. Kratom's active compound, mitragynine, can interact with enzymes that metabolize drugs, which may lead to different effects compared to standard opioid treatments. ^{1 2 3 4 7}

Research Team

Eligibility Criteria

This trial is for healthy adults aged 21-45, weighing between 130-250 pounds with a BMI of 19-30. Participants must have previously used kratom and opioids without issues or addiction, not be on medications that affect these substances' metabolism, and agree to avoid certain substances like caffeine, alcohol, cannabis products, and dietary supplements before visits.

Inclusion Criteria

I have used kratom and opioids before without any bad reactions or addiction.

I am willing to avoid dietary supplements, cannabis, THC/CBD products, and caffeinated drinks.

Willing to use an additional method of contraception

Exclusion Criteria

My weight is either below 130 pounds or above 250 pounds.

Inability to speak, read, and understand English

I have never used kratom or opioids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete four study arms involving kratom and oxycodone administration

4 weeks

Multiple visits (in-person) for each arm

Washout

Washout periods between study arms to prevent carryover effects

At least 10 days between certain arms

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Kratom (Other)
• Oxycodone (Opioid Analgesic)

Trial Overview The study aims to see if kratom affects how the body processes oxycodone. Participants will try four different scenarios: only kratom tea; just an oxycodone tablet; both together; and several days of kratom followed by both. Researchers want to know how this combination impacts drug metabolism and effects on the body.

Participant Groups

Group I: Arm 4 Experimental Treatment 2 Interventions

The same 16 participants will self-administer a single low dose (2 g) of kratom as a tea once daily at home. On the fifth day, subjects will return to the research setting, where they will be administered a single low dose (2 g) of kratom, followed 15 minutes later by a single low dose (10 mg) of oxycodone by mouth. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours.

Group II: Arm 3 Experimental Treatment 2 Interventions

The same 16 participants will be administered a single low dose (2 g) of kratom as a tea. After 15 minutes, the subjects will be administered a single low dose (10 mg) of oxycodone as a tablet by mouth. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours. A washout of at least 10 days will separate Arms 3 and 4.

Group III: Arm 1 Experimental Treatment 1 Intervention

Sixteen non-naive\* participants (8 males, 8 females) will be administered a single low dose (2 g) of a well-characterized kratom product by mouth as a tea. Pupil diameter will be measured from 0-12 hours. A washout of at least 10 days will separate Arms 1 and 2. \*Non-naive subjects are defined as intermittent users who consume 2-8 g kratom at least once per month but no more than three times daily within the last six months prior to screening and are willing to abstain for several weeks

Group IV: Arm 2 Active Control 1 Intervention

The same 16 participants will be administered a single low dose (10 mg) of immediate-release oxycodone by mouth as a tablet. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours. A washout of at least 2 days will separate Arms 2 and 3.

Who Is Running the Clinical Trial?

Washington State University

Lead Sponsor

Trials

114

Recruited

58,800+

Dr. Mangiardi

Washington State University

Chief Executive Officer

PhD in Biochemistry from Washington State University

Dr. Cindy Jacobs

Washington State University

Chief Medical Officer since 2017

PhD in Veterinary Pathology/Microbiology from Washington State University, MD from University of Washington Medical School

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Dr. Amy P. Patterson

National Center for Complementary and Integrative Health (NCCIH)

Chief Medical Officer

MD from Johns Hopkins University

Dr. Helene Langevin

National Center for Complementary and Integrative Health (NCCIH)

Chief Executive Officer since 2018

MD from McGill University

Findings from Research

A study involving 12 healthy adults found that a low dose of kratom tea (2 g) modestly increased the blood levels of midazolam, a drug metabolized by CYP3A, indicating that kratom can inhibit this enzyme and potentially lead to drug interactions.

Kratom did not affect the metabolism of dextromethorphan, another drug metabolized by a different enzyme (CYP2D6), suggesting that its interaction effects may be specific to certain drugs, raising concerns about the safety of using kratom with other medications that rely on CYP3A for elimination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Tanna, RS., Nguyen, JT., Hadi, DL., et al.[2023]

Kratom, a plant with stimulant and opioid-like effects, has been linked to overdose deaths, often in combination with other drugs, raising concerns about its safety as a self-managed treatment for pain and opioid withdrawal.

Kratom and its alkaloids can inhibit key liver enzymes (CYP2D6 and CYP3A) and P-glycoprotein, potentially increasing the effects of other drugs taken alongside it, which could lead to adverse reactions. Further research is needed to understand these interactions and ensure safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating Kratom-Drug Interactions: From Bedside to Bench and Back. Tanna, RS., Cech, NB., Oberlies, NH., et al.[2023]

Mitragynine, a key alkaloid in kratom, was identified as a time-dependent inhibitor of the cytochrome P450 3A enzyme, which is crucial for drug metabolism, potentially leading to serious drug interactions.

Using a mechanistic model, it was predicted that a typical dose of kratom could significantly increase the plasma levels of drugs like midazolam by up to 5.7 times, highlighting the need for further research on the safety of kratom in combination with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations. Tanna, RS., Tian, DD., Cech, NB., et al.[2022]

Herbal medicines, such as St John's wort and ginkgo, can significantly interact with conventional drugs, potentially altering their effectiveness and safety, especially for medications with narrow therapeutic indices like warfarin and cyclosporine.

The mechanisms behind these interactions often involve the induction or inhibition of enzymes like cytochrome P450s, which can affect drug metabolism in the intestine and liver, highlighting the need for careful monitoring when combining herbal remedies with conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herb-drug interactions and mechanistic and clinical considerations. Chen, XW., Sneed, KB., Pan, SY., et al.[2022]

A study analyzing 489 kratom-related adverse drug reactions (ADRs) reported to the FDA from 2004 to 2021 found that kratom use is associated with significant safety concerns, including a 63-fold higher than expected rate of accidental deaths.

The analysis revealed strong signals for addiction and withdrawal symptoms, as well as a notable number of reports related to toxicity and seizures, indicating that while kratom is popular for treating pain and anxiety, it poses potential health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021. Li, X., Ndungu, P., Taneja, SB., et al.[2023]

Kratom, particularly its major alkaloid mitragynine, can inhibit important liver enzymes (CYP2D6 and CYP3A), leading to potential drug interactions when taken with medications like venlafaxine and quetiapine, which can result in serious conditions such as serotonin syndrome.

This case report highlights that discontinuing the interacting medications and using buprenorphine/naloxone can effectively support recovery from kratom use disorder, suggesting a potential treatment pathway for individuals facing similar issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and Subsequent Treatment of Kratom Use Disorder With Buprenorphine/Naloxone. Brogdon, HD., McPhee, MM., Paine, MF., et al.[2022]

References

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

Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. [2023]

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

Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. [2023]

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

Translating Kratom-Drug Interactions: From Bedside to Bench and Back. [2023]

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

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Herb-drug interactions and mechanistic and clinical considerations. [2022]

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

An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and Subsequent Treatment of Kratom Use Disorder With Buprenorphine/Naloxone. [2022]