Kratom-Oxycodone Interaction Study for Herbal Interaction

Overseen By Deena Hadi, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington State University

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

Disqualifiers: Chronic illness, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how kratom, a plant-based product, affects the body's processing of oxycodone, a common pain medication. Researchers aim to determine if kratom alters the breakdown of oxycodone and its effects on the body. Participants will try different combinations of kratom and oxycodone to gather data. This trial suits healthy adults who have previously used kratom and opioids without issues and are willing to abstain from these substances for several weeks. As an Early Phase 1 trial, this research focuses on understanding the interaction between kratom and oxycodone, offering participants a chance to contribute to groundbreaking insights.

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.

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

Research has shown several safety concerns with kratom. Users have reported side effects such as nausea, dry mouth, and constipation. More serious risks include liver damage and seizures. Some kratom products may also contain harmful contaminants like heavy metals.

Mixing kratom with opioids like oxycodone poses dangers. Studies indicate that kratom can alter how the body processes other drugs, increasing the risk of serious side effects, including a higher chance of overdose.

Although oxycodone is an FDA-approved medication, it can cause serious side effects like breathing difficulties and drowsiness, especially at higher doses.

These findings suggest that using kratom with oxycodone could be risky. Considering these safety issues is important for those thinking about joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Kratom-Oxycodone Interaction Study because it explores how kratom, a natural herbal supplement, interacts with oxycodone, a commonly prescribed opioid for pain relief. Unlike standard pain management options, which typically involve opioids or non-opioid medications, kratom is believed to act on opioid receptors in the brain but may offer a different side effect profile. This trial aims to uncover whether combining kratom with oxycodone could potentially enhance pain relief or reduce opioid use, providing a unique approach in the search for safer pain management solutions.

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

This trial will investigate the interaction between kratom and oxycodone when taken together. Research has shown that kratom can alter drug metabolism by interacting with enzymes that break down medications, potentially affecting oxycodone's processing in the body. Studies have also found that kratom acts like opioids, providing pain relief and euphoria. In this trial, some participants will receive kratom alone, others oxycodone alone, and some a combination of both. This design aims to determine how kratom might change the strength or duration of oxycodone's effects. However, using kratom with opioids can increase the risk of serious side effects, including overdose. These findings underscore the need to understand the interaction between kratom and oxycodone. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 abstain from consuming alcoholic beverages for one day prior to any inpatient visit

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Kratom
• Oxycodone

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.

How Is the Trial Designed?

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+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

Kratom, a plant used for its psychoactive and pain-relieving effects, has gained popularity in the U.S. for treating conditions like opioid withdrawal and chronic pain, but its processing and sales are largely unregulated.

This study highlights a specific case of kratom interacting with the antidepressant amitriptyline in a patient recovering from opioid use disorder, emphasizing the need for more clinical research on kratom's effects and potential drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Vanani, NB., Stevanovic, SG., Stevanovic, N.[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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10198846/

Clinical Assessment of the Drug Interaction Potential ... Kratom increased the AUCinf of the primary CYP3A-mediated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam, by ~18–27% and decreased the metabolic ratios ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0090955624010195

Translating Kratom-Drug Interactions: From Bedside to ... This review focuses on the potential for kratom to precipitate pharmacokinetic interactions with object drugs involved in these reported polyintoxications.

3. nature.com nature.com/articles/s41598-020-76119-w

Chemical composition and biological effects of kratom ... The study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7203303/

Kratom—Pharmacology, Clinical Implications, and Outlook Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04392011

Assessing the Pharmacokinetics and Drug Interaction ... Results will (1) provide useful information regarding risks associated with co-consuming kratom with opioids and other CYP2D6 and CYP3A4 drug substrates and (2) ...

6. mayoclinic.org mayoclinic.org/diseases-conditions/prescription-drug-abuse/in-depth/kratom/art-20402171

Kratom: Unsafe and ineffective Side effects and safety concerns · Weight loss. · Dry mouth. · Nausea and vomiting. · Constipation. · Liver damage. · Muscle pain. · High blood ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9130800/

Health Effects Associated With Kratom (Mitragyna speciosa ... Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable.

8. dea.gov dea.gov/sites/default/files/2020-06/Kratom-2020_0.pdf

Drug Fact Sheet: Kratom Users of kratom have also experienced anorexia, weight loss, insomnia, hepatotoxicity, seizure, and hallucinations.

9. americanaddictioncenters.org americanaddictioncenters.org/kratom/dangers

Dangers, Side Effects & Kratom Overdose What research has discovered, as of now, is that some kratom products contain contaminants, including heavy metals and harmful bacteria.

10. fda.gov fda.gov/news-events/public-health-focus/fda-and-kratom

FDA and Kratom FDA has warned consumers not to use kratom because of the risk of serious adverse events, including liver toxicity, seizures, and substance use disorder (SUD).