CClinicalTrials.gg
Sign In
Active, not recruitingNCT07583407Updated Sep 3, 2026

Pharmacokinetics of Kava and Kratom Alone and in Combination

An interventional study of Kava and Kratom Herbal Supplement and Kava Herbal Supplement in Herb-Herb Interaction and Pharmacokinetics, sponsored by Botanic Tonics, LLC. Active, not recruiting at 1 site in Canada. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-03.

Sponsored by Botanic Tonics, LLC · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
21 Years to 55 Years
Sex
All
01

Study summary

This study is being conducted to evaluate how different formulations of the Feel Free® Tonic containing Kava, Kratom, or a combination of both are processed in the body in healthy adults. The goal is to compare the pharmacokinetic profiles and safety of the combined herbal formulation with Kava alone and Kratom alone to better understand how these ingredients behave when taken individually versus together.

Read the detailed description

This is a randomized, double blind, 3 period crossover pharmacokinetic study in healthy adults designed to compare the pharmacokinetic profiles of a combined Kava and Kratom formulation with Kava alone and Kratom alone under fasted conditions. The primary objective is to evaluate systemic exposure and key pharmacokinetic parameters following each treatment. Secondary objectives include the assessment of safety and tolerability across all study products. The investigational products are oral liquid herbal supplements containing Kava, Kratom, or a combination of both. The study will also explore subjective effects, well-being, mood, and participant perceptions of the study products. Each participant will receive all three treatments in a randomized sequence with washout periods between dosing, allowing within subject comparison of pharmacokinetic outcomes.

02

Conditions studied

  • Herb-Herb Interaction
  • Pharmacokinetics

Keywords

  • Kava
  • Kratom
  • Pharmacokinetics
  • Healthy Adults
  • Herbal Supplement
03

In context

Lead sponsor

Botanic Tonics, LLC is the lead sponsor of 2 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Adults who are between 21 - 55 years of age (inclusive) at the time of signing the informed consent.
  2. In otherwise good general health, as deemed by the investigator (based on review of medical history, vital signs, laboratory safety tests, and physical examination performed at screening and/or before the first dose of study product).
  3. Are able to consume the study product completely within the specified timeframe.
  4. Not currently using, defined as ≤ 3 uses in the past 3 months prior to Visit 2, any nicotine-containing products (patches, gums, vapes, etc.), kava products, and/or kratom products, and willing to abstain starting 14 days prior to Visit 2 and throughout the study.
  5. Have a BMI range of 18.5 - 29.9 kg/m2 at screening and Visit 2.
  6. Agree to follow the restrictions on concomitant treatments.
  7. Agree to follow the restrictions on lifestyle.
  8. Have maintained consistent dietary habits, including supplement intake, and lifestyle for the last 3 months before screening and agree to maintain them throughout the study (unless required per the restrictions)

  9. Individuals with childbearing potential must agree to comply with the following requirements:

    • Have a negative pregnancy test at screening and on Day 1 of each treatment period prior to administration of study product.
    • Use a highly effective method of contraception from at least 14 days prior to the first dose through 30 days after the last dose of study product.
  10. Individuals with the potential to impregnate others must agree to use a highly effective method of contraception, from at least 14 days prior to the first dose through 30 days after the last dose of study product.
  11. Male-born participants must agree to abstain from sperm donation, and female-born participants must agree to abstain from ovum donation, from Screening through at least 30 days after the last dose of study product.
  12. Agree to abstain from alcohol consumption for 48 hours prior to, and for the entire duration of, each treatment period.
  13. Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.
  14. Must have suitable veins for repeated venipuncture.
  15. Willing and able to attend video conference calls with study coordinators.
  16. Agrees not to donate blood until 3 months after study completion.

Exclusion criteria

Exclusion Criteria:

  1. Individuals who are lactating, planning to become pregnant during the study, or pregnant as confirmed by a positive pregnancy test during study visits.
  2. Have a known sensitivity, intolerability, or allergy to any of the study products, their excipients, or rescue medication.
  3. Demonstrates a positive urine drug screen test for compounds listed in Table 8 4 at the Screening Visit or Visit 2, a positive urine cotinine test at the Screening Visit or Visit 2, or a positive breath alcohol test at Screening Visit or Visit 2.
  4. Have abnormal respiratory rate (RR) or SpO2 measurements at Screening or Baseline at the discretion of the investigator.
  5. Screening laboratory results showing liver enzyme levels [Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Gamma-Glutamyl Transferase (GGT), total bilirubin] ≥ 2 times the upper limit of normal (ULN), or any other clinically significant abnormal safety laboratory values as per the Investigator's discretion.
  6. Have hemoglobin below 135 g/L for males or 125 g/L for females, or hematocrit below 0.39 l/l for males or 0.33 l/l for females at screening.
  7. Demonstrates a positive screen for HIV at screening.
  8. Is currently enrolled in another clinical trial or has received/used an investigational product in another research study within 28 days before Visit 2.
  9. Individuals with any abnormality, obstruction, or disorder of the gastrointestinal tract that may preclude swallowing (e.g., dysphagia) or impair gastrointestinal motility, digestion, or absorption (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease [including Crohn's disease or ulcerative colitis], chronic pancreatitis, or steatorrhea). In addition, any history of gastrointestinal surgery or anatomical abnormality that, in the opinion of the Investigator, may affect the oral absorption of the study product.
  10. Have been diagnosed with Type I/Type II diabetes or thyroid disease
  11. High BP at the Screening Visit or Visit 2 (≥140 systolic or ≥90 diastolic mmHg)
  12. Have low BP (\<90 systolic or \<60 diastolic mmHg) at Baseline unless deemed clinically insignificant by the investigator and the participant is asymptomatic.
  13. Have a history of heart disease, blood-clotting disorders, renal or hepatic impairment/disease, liver injury or any clinically significant liver or kidney disorder, as determined by the Investigator.
  14. Have known genetic polymorphisms of CYP450 enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2B6, and/or CYP3A4.
  15. Individuals with active asthma or a history of clinically significant asthma exacerbation (i.e., requiring systemic corticosteroids, emergency department intervention, or hospitalization) within the past 12 months.
  16. Individuals receiving treatment for, or who have been hospitalized in the last 12 months for, psychiatric disorders (e.g., Major Depressive Disorder, Bipolar I/II, Generalized Anxiety Disorder, Schizophrenia, or other psychotic disorders), particularly when the diagnosis is established using accepted gold-standard diagnostic methods (e.g., structured clinical interviews), or with complications such as suicidal ideation or behavior.
  17. Have current use of medications, including psychiatric pharmacotherapy, that are predominantly metabolized via CYP enzymes (e.g., CYP3A4, CYP2D6, CYP1A2) and/or have CNS depressant or opioid-like effects, or act on central receptors such as μ- and δ-opioid, serotonergic 5-HT2A, post-synaptic alpha-2 adrenergic, or GABA receptors, where such treatment may create clinically significant pharmacokinetic or pharmacodynamic interactions with study treatments, including antidepressants, antipsychotics, mood stabilizers, anxiolytics, or benzodiazepines.
  18. Have a history of cancer with recovery occurring within 5 years prior to the Screening visit, except for localized skin cancer without metastases (e.g., completely excised basal cell carcinoma or squamous cell carcinoma of the skin) or in situ cervical cancer (e.g., adequately treated carcinoma in situ of the cervix).
  19. Reports significant blood loss or blood donation totalling between 101 mL to 449 mL of blood within 30 days before baseline or a blood donation of more than 450 mL within 90 days before Visit 2.
  20. Reports donating plasma (e.g., plasmapheresis) within 15 days before Visit 2.
  21. Major surgery in 3 months before screening or planned major surgery during the study.
  22. History of alcohol or substance abuse (e.g., opioids, kratom) (including having been hospitalized for such an in-patient or out-patient intervention program).
  23. Evidence of addictive tendency as indicated by an LDQ score ≥21.
  24. Use of anxiolytic or sleep aids (natural health products or drugs) in the 4 weeks before Visit 2.

  25. Currently consumes more than two (2) standard alcoholic beverages per day on average for 4 weeks.

    Note: A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor.

  26. Excessive caffeine intake, defined as habitual consumption of >500 mg per day.
  27. Any other medical conditions, including active infections, or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures, pose a significant risk to the participant or compromise the quality of study data.
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
18 participants (estimated)

Study arms

  • Active comparator
    Half- Strength Feel Free Classic Tonic (TP1)

    Active Product of 380 mg Kava root extract and 1480 mg of dried Kratom Leaf powder per bottle

    Dietary Supplement: Kava and Kratom Herbal Supplement

  • Active comparator
    Kava Only Variant - Feel Free Tonic (TP2)

    Active Product of 380 mg Kava root extract per bottle

    Dietary Supplement: Kava Herbal Supplement

  • Active comparator
    Kratom Only Variant - Feel Free Tonic (TP3)

    Active Product of 1480 mg dried Kratom Leaf powder per bottle

    Dietary Supplement: Kratom Herbal Supplement

Interventions

  • Dietary supplementKava and Kratom Herbal Supplement

    Half- Strength Feel Free Classic Tonic (TP1)

  • Dietary supplementKava Herbal Supplement

    Kava Only Variant - Feel Free Tonic (TP2)

  • Dietary supplementKratom Herbal Supplement

    Kratom Only Variant - Feel Free Tonic (TP3)

06

What researchers measure

Primary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Kavain

    AUC0-24 for kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  2. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Dihydrokavain

    AUC0-24 for dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  3. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Mitragynine

    AUC0-24 for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for 7-Hydroxymitragynine

    AUC0-24 for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

Secondary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Kavain

    AUC0-72 for kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  2. Maximum Observed Plasma Concentration (Cmax) for Kavain

    Peak plasma concentration of kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

  3. Time to Maximum Plasma Concentration (Tmax) for Kavain

    Time to reach maximum observed plasma concentration of kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  4. Terminal Elimination Half-Life (T½) for Kavain

    Terminal elimination half-life of kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Dihydrokavain

    AUC0-72 for dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  6. Maximum Observed Plasma Concentration (Cmax) for Dihydrokavain

    Peak plasma concentration of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

  7. Time to Maximum Plasma Concentration (Tmax) for Dihydrokavain

    Time to reach maximum observed plasma concentration of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  8. Terminal Elimination Half-Life (T½) for Dihydrokavain

    Terminal elimination half-life of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  9. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Mitragynine

    AUC0-72 for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  10. Maximum Observed Plasma Concentration (Cmax) for Mitragynine

    Peak plasma concentration of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

  11. Time to Maximum Plasma Concentration (Tmax) for Mitragynine

    Time to reach maximum observed plasma concentration of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  12. Terminal Elimination Half-Life (T½) for Mitragynine

    Terminal elimination half-life of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  13. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for 7-Hydroxymitragynine

    AUC0-72 for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  14. Maximum Observed Plasma Concentration (Cmax) for 7-Hydroxymitragynine

    Peak plasma concentration of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

  15. Time to Maximum Plasma Concentration (Tmax) for 7-Hydroxymitragynine

    Time to reach maximum observed plasma concentration of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

  16. Terminal Elimination Half-Life (T½) for 7-Hydroxymitragynine

    Terminal elimination half-life of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  17. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Kavain

    AUC0-∞ for kavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  18. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Kavain

    Ratio of exposure from 0-24 hours relative to total exposure for kavain.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  19. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Dihydrokavain

    AUC0-∞ for Dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  20. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Dihydrokavain

    Ratio of exposure from 0-24 hours relative to total exposure for Dihydrokavain.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  21. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Mitragynine.

    AUC0-∞ for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  22. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Mitragynine

    Ratio of exposure from 0-24 hours relative to total exposure for mitragynine.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  23. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for 7-Hydroxymitragynine.

    AUC0-∞ for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  24. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for 7-Hydroxymitragynine

    Ratio of exposure from 0-24 hours relative to total exposure for 7-Hydroxymitragynine.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

  25. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Kavain

    AUC0-12,ss for Kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  26. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Kavain

    Cmax,ss for kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  27. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Kavain

    Tmax,ss of kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  28. Terminal Elimination Half-Life at Steady State (T½,ss) for Kavain

    T½,ss for kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  29. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Kavain

    AUC0-∞,ss for kavain following multiple-day dosing administration of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  30. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Kavain

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for kavain.

    Time frame: Day 14 of each treatment period

  31. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Dihydrokavain

    AUC0-12,ss for dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  32. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Dihydrokavain

    Cmax,ss for dyhydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  33. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Dihydrokavain

    Tmax,ss of dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  34. Terminal Elimination Half-Life at Steady State (T½,ss) for Dihydrokavain

    T½,ss for dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  35. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Dihydrokavain

    AUC0-∞,ss for dihydrokavain following multiple-day dosing administration of Kava alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  36. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Dihydrokavain

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for dihydrokavain.

    Time frame: Day 14 of each treatment period

  37. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Mitragynine

    AUC0-12,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  38. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Mitragynine

    Cmax,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  39. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Mitragynine

    Tmax,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  40. Terminal Elimination Half-Life at Steady State (T½,ss) for Mitragynine

    T½,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  41. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Mitragynine

    AUC0-∞,ss for mitragynine following multiple-day dosing administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  42. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Mitragynine

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for mitragynine.

    Time frame: Day 14 of each treatment period

  43. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for 7-Hydroxymitragynine

    AUC0-12,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  44. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for 7-Hydroxymitragynine

    Cmax,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  45. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for 7-Hydroxymitragynine

    Tmax,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  46. Terminal Elimination Half-Life at Steady State (T½,ss) for 7-Hydroxymitragynine

    T½,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  47. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for 7-Hydroxymitragynine

    AUC0-∞,ss for 7-Hydroxymitragynine following multiple-day dosing administration of Kratom alone or combined Kava and Kratom

    Time frame: Day 14 of each treatment period

  48. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for 7-Hydroxymitragynine

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for 7-Hydroxymitragynine.

    Time frame: Day 14 of each treatment period

Other outcomes

  1. Modified Drug Effects Questionnaire (DEQ)

    To assess the effect of TP on subjective drug effects compared to comparator. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses the participants subjective experience after consuming the TP.

    Time frame: Days 1 and 14 of each treatment period

  2. Overall Well Being, Health, and Pain

    To assess the effect of TP on overall well-being, health, and pain compared to comparator. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses overall quality of life with questions specifically on physical health and pain. Higher scores indicate better overall well-being, health, and pain.

    Time frame: Pre-dose Day 1 to Pre-dose Days 7 and 14 of each treatment period

  3. Ecological Momentary Assessment (EMA) Survey

    To assess the effect of TP on mood compared to comparator. A non-validated questionnaire consisting of 13 questions assessing the participants emotional and mental/physical states they are feeling "right now." This questionnaire uses bipolar visual analogue scales in which participants how they feel "right now" on lines between two opposite feelings or physical sensations.

    Time frame: Days 2, 4, 6, 8, 10, 12, and 14 of each treatment period

  4. Study Product Perception & Attitude Survey

    To assess the effect of TP on study product perceptions and attitudes compared to comparator. A non-validated questionnaire consisting of multiple items assessing participants' subjective experiences with the study product, including effects on daily functioning, energy, sleep, mood, mild stress/anxiety, focus, mild pain, muscle recovery, tolerability, and product quality. Items are scored on a 5#point Likert scale ranging from "Strongly Disagree" to "Strongly Agree." Higher scores indicate more favorable perceptions of the study product (except for the side effects item, where higher scores indicate greater perceived side effects).

    Time frame: Days 7 and 14 of each treatment period

  5. Appraisal of Effects Survey

    To assess participant-reported perceptions of the effects of the study product compared to comparator. A non-validated, self-administered questionnaire consisting of multiple items assessing participants' subjective experiences with the study product, including overall effect on how they feel, liking of the product, pain, muscle fatigue, mental focus/concentration, and calmness/stress. Items are scored using a 100-point visual analogue scale ranging from "Not at all" (0) to "Extremely" (100). Higher scores indicate greater perceived effects of the study product.

    Time frame: Days 2, 4, 6, 8, 10, 12, and 14

  6. Safety Assessments - Incidence of Treatment-Emergent Adverse Events

    Number and percentage of participants experiencing treatment-emergent adverse events from first dose through follow-up.

    Time frame: From first dose through follow-up visit

  7. Safety Assessment: Change in Subjective Opiate Withdrawal Scale (SOWS)

    To test the safety of TP by assessing the change in SOWS. This validated questionnaire is used to assess participants intensity of potential opioid withdrawal symptoms. Items are scored on a 5-point Likert scale ranging from 0 ('Not at all') to 4 ('Extremely'). Higher scores indicate higher potential withdrawal symptoms.

    Time frame: Day 1 and Day 14 of each treatment period

  8. Safety Assessment: Change in Clinical Opiate Withdrawal Scale (COWS)

    To test the safety of TP by assessing the change in COWS. This validated questionnaire is used to assess common signs and symptoms of opiate withdrawal. Items are scored from 0 to 48. Higher scores indicate higher withdrawal symptoms.

    Time frame: Day 1 and Day 14 of each treatment period

  9. Safety Assessments - Electrocardiogram (ECG)

    To assess cardiac function based on the change in ECG intervals.

    Time frame: Screening, and Day 1, and Day 14 of each treatment period

  10. Safety Assessments - Vitals (Heart Rate)

    Change in Heart Rate (beats per minute) from baseline to each study visit.

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

  11. Safety Assessments - Vitals (Blood Pressure)

    Change in Blood Pressure (mmHg) from baseline to each study visit.

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

  12. Safety Assessments - Vitals (Respiratory Rate)

    Change in Respiratory Rate (breaths per minute) from baseline to each study visit.

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

  13. Safety Assessments - Vitals (Oxygen Saturation)

    Change in Oxygen Saturation (SpO2) from baseline to each study visit.

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

  14. Safety Assessments - Vitals (Body Temperature)

    Change in body temperature (°C) from baseline to each study visit.

    Time frame: Screening, and from Day 1 to Day 14 of each treatment period

  15. Safety Assessments - Weight (Change from Baseline)

    Change from baseline in body weight (kg)

    Time frame: Day 1 to Day 14 of each treatment period

  16. Safety Assessments - Body Mass Index (BMI - Change from Baseline)

    Change from baseline in body mass index (kg/m²)

    Time frame: Day 1 to Day 14 of each treatment period

  17. Safety Assessments - Height

    Height (cm) measured at screening only used for calculating body mass index (kg/m²)

    Time frame: Screening only

  18. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Hemoglobin)

    To assess the safety of TP through the change from baseline to each study visit in hemoglobin (g/L)

    Time frame: Baseline to Day 14 of each treatment period

  19. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Hematocrit)

    To assess the safety of TP through the change from baseline to each study visit in hematocrit (%)

    Time frame: Baseline to Day 14 of each treatment period

  20. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Red Blood Cell Count)

    To assess the safety of TP through the change from baseline to each study visit in red blood cell count (×10E\^12/L).

    Time frame: Baseline to Day 14 of each treatment period

  21. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Red Cell Distribution Width)

    To assess the safety of TP through the change from baseline to each study visit in red cell distribution width.

    Time frame: Baseline to Day 14 of each treatment period

  22. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Volume)

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular volume (fL).

    Time frame: Baseline to Day 14 of each treatment period

  23. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Hemoglobin)

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular hemoglobin (pg).

    Time frame: Baseline to Day 14 of each treatment period

  24. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Hemoglobin Concentration)

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular hemoglobin concentration (g/L).

    Time frame: Baseline to Day 14 of each treatment period

  25. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - White Blood Cell Count)

    To assess the safety of TP through the change from baseline to each study visit in white blood cell count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  26. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Neutrophil Count)

    To assess the safety of TP through the change from baseline to each study visit in Neutrophil Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  27. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Eosinophil Count)

    To assess the safety of TP through the change from baseline to each study visit in Eosinophil Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  28. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Basophil Count)

    To assess the safety of TP through the change from baseline to each study visit in Basophil Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  29. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Lymphocyte Count)

    To assess the safety of TP through the change from baseline to each study visit in Lymphocyte Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  30. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Monocyte Count)

    To assess the safety of TP through the change from baseline to each study visit in Monocyte Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  31. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Platelet Count)

    To assess the safety of TP through the change from baseline to each study visit in Platelet Count (×10\^9/L).

    Time frame: Baseline to Day 14 of each treatment period

  32. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Platelet Volume)

    To assess the safety of TP through the change from baseline to each study visit in mean platelet volume (fL)

    Time frame: Baseline to Day 14 of each treatment period

  33. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Blood Smear Findings)

    To assess the safety of TP through the change from baseline to each study visit in blood smear findings.

    Time frame: Baseline to Day 14 of each treatment period

  34. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Blood Urea Nitrogen)

    To assess the safety of TP through the change from baseline to each study visit in blood urea nitrogen (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  35. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Creatinine)

    To assess the safety of TP through the change from baseline to each study visit in creatinine (umol/L)

    Time frame: Baseline to Day 14 of each treatment period

  36. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Estimated Glomerular Filtration Rate)

    To assess the safety of TP through the change from baseline to each study visit in estimated glomerular filtration rate (ml/min/1.7m\^2).

    Time frame: Baseline to Day 14 of each treatment period

  37. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Albumin)

    To assess the safety of TP through the change from baseline to each study visit in albumin (g/L).

    Time frame: Baseline to Day 14 of each treatment period

  38. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Random Glucose)

    To assess the safety of TP through the change from baseline to each study visit in random glucose (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  39. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Fasting Glucose)

    To assess the safety of TP through the change from baseline to each study visit in fasting glucose (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  40. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Total Protein)

    To assess the safety of TP through the change from baseline to each study visit in total protein (g/L).

    Time frame: Baseline to Day 14 of each treatment period

  41. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Sodium)

    To assess the safety of TP through the change from baseline to each study visit in Sodium (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  42. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Potassium)

    To assess the safety of TP through the change from baseline to each study visit in Potassium (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  43. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Chloride)

    To assess the safety of TP through the change from baseline to each study visit in Chloride (mmol/L).

    Time frame: Baseline to Day 14 of each treatment period

  44. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Aspartate Transaminase)

    To assess the safety of TP through the change from baseline to each study visit in Aspartate Transaminase (AST) in U/L.

    Time frame: Baseline to Day 14 of each treatment period

  45. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Alanine Transaminase)

    To assess the safety of TP through the change from baseline to each study visit in Alanine Transaminase (ALT) in mmol/L.

    Time frame: Baseline to Day 14 of each treatment period

  46. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Gamma-Glutamyl Transferase)

    To assess the safety of TP through the change from baseline to each study visit in Gamma-Glutamyl Transferase(GGT) in U/L.

    Time frame: Baseline to Day 14 of each treatment period

  47. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Total Bilirubin)

    To assess the safety of TP through the change from baseline to each study visit in Total Bilirubin in µmol/L.

    Time frame: Baseline to Day 14 of each treatment period

  48. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Direct Bilirubin)

    To assess the safety of TP through the change from baseline to each study visit in Direct Bilirubin in µmol/L.

    Time frame: Baseline to Day 14 of each treatment period

  49. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Total Bile Acids)

    To assess the safety of TP through the change from baseline to each study visit in Total Bile Acids in µmol/L.

    Time frame: Baseline to Day 14 of each treatment period

  50. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - International Normalized Ratio)

    To assess the safety of TP through the change from baseline to each study visit in International Normalized Ratio (INR).

    Time frame: Baseline to Day 14 of each treatment period

  51. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Glutamate dehydrogenase )

    To assess the safety of TP through the change from baseline to each study visit in Glutamate dehydrogenase (GLDH) in U/L.

    Time frame: Baseline to Day 14 of each treatment period

  52. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Coproporphyrin-I)

    To assess the safety of TP through the change from baseline to each study visit in Coproporphyrin-I (CP-I) concentration.

    Time frame: Baseline to Day 14 of each treatment period

  53. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Coproporphyrin-III)

    To assess the safety of TP through the change from baseline to each study visit in Coproporphyrin-I (CP-III) concentration.

    Time frame: Baseline to Day 14 of each treatment period

  54. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Alkaline Phosphatase)

    To assess the safety of TP through the change from baseline to each study visit in Alkaline Phosphatase (ALP) in U/L.

    Time frame: Baseline to Day 14 of each treatment period

07

Study locations

1 site
  • ApexTrials
    Guelph, Ontario N1G 0B4, Canada
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07583407
Lead sponsor
Botanic Tonics, LLC
Collaborators
Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
Responsible party
Sponsor
First posted
May 13, 2026
Start date
May 4, 2026
Primary completion
Nov 20, 2026 (estimated)
Completion
Nov 20, 2026 (estimated)
Last update
Sep 3, 2026

Study contacts

Ramsey Atallah
study director · Botanic Tonics

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Botanic Tonics, LLC

Start the discussion