Pharmacokinetics of Kava and Kratom Alone and in Combination

A Randomized, Double-Blind, 3-Period Crossover, Pharmacokinetic Study in Healthy Adults to Compare Combined Kava and Kratom Supplementation With Kava or Kratom Alone Under Fasted Conditions

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.

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics; Herb-Herb Interaction
• Intervention / Treatment: Dietary supplement: Kava and Kratom Herbal Supplement; Dietary supplement: Kava Herbal Supplement; Dietary supplement: Kratom Herbal Supplement

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie Recker; Phone Number: 109 519-341-3367; Email: srecker@nutrasource.ca
• Study Contact Backup: Name: Ambreen Atif, MD; Phone Number: 129 519-341-3367; Email: aatif@nutrasource.ca

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 0B4
      • Recruiting
      • ApexTrials
      • Contact: Katie Keene, H.BSc., CCRP; Phone Number: 226-706-2545; Email: kkeene@apextrials.com
      • Principal Investigator: Anthony Bier, MD, CCFP(EM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Half- Strength Feel Free Classic Tonic (TP1)
Active Comparator: Kava Only Variant - Feel Free Tonic (TP2); Active Product of 380 mg Kava root extract per bottle	Dietary supplement: Kava Herbal Supplement; Kava Only Variant - Feel Free Tonic (TP2)
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; Kratom Only Variant - Feel Free Tonic (TP3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Kavain	Peak plasma concentration of kavain following single-dose administration of Kava alone or combined Kava and Kratom	Day 1 of each treatment period (0-12 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Dihydrokavain	Peak plasma concentration of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom	Day 1 of each treatment period (0-12 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Mitragynine	Peak plasma concentration of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom	Day 1 of each treatment period (0-12 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 of each treatment period (0-12 hours post-dose)
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	Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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.	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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.	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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.	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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.	Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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.	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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.	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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.	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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	Day 14 of each treatment period
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.	Day 14 of each treatment period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Days 1 and 14 of each treatment period
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.	Pre-dose Day 1 to Pre-dose Days 7 and 14 of each treatment period
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.	Days 2, 4, 6, 8, 10, 12, and 14 of each treatment period
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).	Days 7 and 14 of each treatment period
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.	Days 2, 4, 6, 8, 10, 12, and 14
Safety Assessments - Incidence of Treatment-Emergent Adverse Events	Number and percentage of participants experiencing treatment-emergent adverse events from first dose through follow-up.	From first dose through follow-up visit
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.	Day 1 and Day 14 of each treatment period
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.	Day 1 and Day 14 of each treatment period
Safety Assessments - Electrocardiogram (ECG)	To assess cardiac function based on the change in ECG intervals.	Screening, and Day 1, and Day 14 of each treatment period
Safety Assessments - Vitals (Heart Rate)	Change in Heart Rate (beats per minute) from baseline to each study visit.	Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period
Safety Assessments - Vitals (Blood Pressure)	Change in Blood Pressure (mmHg) from baseline to each study visit.	Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period
Safety Assessments - Vitals (Respiratory Rate)	Change in Respiratory Rate (breaths per minute) from baseline to each study visit.	Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period
Safety Assessments - Vitals (Oxygen Saturation)	Change in Oxygen Saturation (SpO2) from baseline to each study visit.	Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period
Safety Assessments - Vitals (Body Temperature)	Change in body temperature (°C) from baseline to each study visit.	Screening, and from Day 1 to Day 14 of each treatment period
Safety Assessments - Weight (Change from Baseline)	Change from baseline in body weight (kg)	Day 1 to Day 14 of each treatment period
Safety Assessments - Body Mass Index (BMI - Change from Baseline)	Change from baseline in body mass index (kg/m²)	Day 1 to Day 14 of each treatment period
Safety Assessments - Height	Height (cm) measured at screening only used for calculating body mass index (kg/m²)	Screening only
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)	Baseline to Day 14 of each treatment period
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 (%)	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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)	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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)	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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).	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period
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.	Baseline to Day 14 of each treatment period

Collaborators and Investigators

• Sponsor: Botanic Tonics, LLC
• Collaborators: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
• Investigators: Study Director: Ramsey Atallah, Botanic Tonics

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): September 4, 2026
• Study Completion (Estimated): September 4, 2026

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Adults; Herbal Supplement; Kratom; Kava
• Other Study ID Numbers: B05-25-04-T0091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No