Effects of Feel Free® Classic Tonic on Stress and Pharmacokinetics in Healthy Adults

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effects of Feel Free® Classic Tonic on Self-Perceived Stress and Pharmacokinetic Profile in Healthy Adults

This study is being conducted to assess the effects of the Feel Free® Classic Tonic on stress in healthy adults. The goal is to see whether the tonic can help reduce self-perceived and physiological stress and provide information on how its ingredients are processed in the body.

Study Overview

• Status: Recruiting
• Conditions: Stress; Anxiety; Physiological Stress
• Intervention / Treatment: Other: Placebo; Other: Kava and Kratom Herbal Supplement; Other: Kava and Kratom Herbal Supplement

Detailed Description

This is a randomized, double-blind, parallel, 3-arm, placebo-controlled study to assess the effects of two dose levels of the Feel Free® Classic Tonic on stress in healthy adults. The primary goal is to evaluate how the tonic affects self-reported and physiological measures of stress and anxiety. A pharmacokinetic sub-study will assess how the tonic's components are absorbed and processed. The tonic contains kava and kratom, botanicals traditionally used for relaxation and mood support, and early data suggest it is generally well tolerated.

• Study Type: Interventional
• Enrollment (Estimated): 165
• 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 screening.
2. Have self-reported stress at screening and baseline scoring 14 - 26 (inclusive) on the PSS-10.
3. In good general health (no uncontrolled diseases or conditions) as deemed by the investigator and is able to consume the study product.
4. Not currently using, defined as ≤ 3 uses in the past 3 months prior to Baseline, any nicotine containing products (patches, gums, vapes etc.), kava products, and/or kratom products, and willing to abstain starting 14 days prior to Baseline and throughout the study.
5. Have a BMI range of 18.5 - 29.9 kg/m2 at screening and baseline.
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.
9. Agree to use acceptable contraceptive methods.
10. Agree to abstain from alcohol consumption for the entire duration of the study.
11. 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.

12. For Sub-Study participants only:

    • Must have suitable veins for repeated venipuncture.
    • Willing and able to attend video conference calls with study coordinators.

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 9 Screening or Baseline visits, a positive urine cotinine test at the Screening or Baseline visits, or a positive breath alcohol test at Baseline visit.
4. Have abnormal 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, or any other clinically significant abnormal safety laboratory values as per the Investigator's discretion.
6. Is currently enrolled in another clinical trial or has received/used an investigational product in another research study within 28 days before baseline.
7. Individuals with an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g., dysphagia) and digestion (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease, chronic pancreatitis, steatorrhea).
8. Have Type I/Type II diabetes or thyroid disease (thyroid function to be assessed by TSH, T3, and T4 levels at Screening visit).
9. High BP at the Screening or Baseline Visit (≥140 systolic or ≥90 diastolic mmHg)
10. Have low BP (<90 systolic or <60 diastolic mmHg) at Baseline unless deemed clinically insignificant by the investigator and the participant is asymptomatic.
11. Have a history of heart disease, blood clotting disorders, renal or hepatic impairment/disease, or liver injury.
12. Have known genetic polymorphisms of CYP450, CYP3A4, CYP2D6, and/or CYP1A2 enzymes.
13. Individuals with active asthma or have experienced an asthma attack in the last 5 years.
14. Are receiving treatments for or have been hospitalized in the last 12 months for psychiatric disorders (e.g., depression, bipolar disorder, schizophrenia, etc.).
15. Have a history of cancer (except localized skin cancer without metastases or in situ cervical cancer) with recovery occurring within 5 years before the screening visit.
16. Reports significant blood loss or blood donation totaling between 101 mL to 449 mL of blood within 30 days before baseline or a blood donation of more than 450 mL within 56 days before baseline.
17. Reports donating plasma (e.g., plasmapheresis) within 15 days before baseline.
18. Major surgery in 3 months before screening or planned major surgery during the study.
19. History of alcohol or substance abuse (e.g., opioids, kratom) (including having been hospitalized for such an in-patient or out-patient intervention program).
20. Evidence of addictive tendency as indicated by an LDQ score ≥21.
21. Use of anxiolytic or sleep aids (natural health products or drugs) in the 4 weeks before baseline.

22. 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.

23. Excessive caffeine intake, defined as habitual consumption of >500 mg per day.
24. Any other medical conditions 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: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; No Active Product per bottle	Other: Placebo; Placebo
Experimental: Feel Free Classic Tonic Dose 1; Active Product of 380 mg Kava root extract and 1480 mg of dried Kratom Leaf powder per bottle	Other: Kava and Kratom Herbal Supplement; Feel Free Classic Tonic Dose 1 (TP1); Other: Kava and Kratom Herbal Supplement; Feel Free Classic Tonic Dose 2 (TP2 - Half Strength)
Experimental: Feel Free Classic Tonic Dose 2 (half strength); Active Product of 190 mg Kava root extract and 740 mg of dried Kratom Leaf powder per bottle	Other: Kava and Kratom Herbal Supplement; Feel Free Classic Tonic Dose 1 (TP1); Other: Kava and Kratom Herbal Supplement; Feel Free Classic Tonic Dose 2 (TP2 - Half Strength)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Perceived Stress Scale-10 (PSS-10) Score	Change in PSS-10 score from baseline to Day 29 to assess the effect of the test product on self-perceived stress. Items are scored on a 5-point Likert scale ranging from 0 ('Never') to 4 ('Very Often'). Higher scores indicate higher perceived stress levels.	Baseline (Day 1) to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in State-Trait Anxiety Inventory - State (STAI-S) - Single Dose	Change in STAI-S score from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 1 after a single dose. The scale assesses how participants feel "right-now". It measures subjective and temporary fluctuations in feelings associated with anxiety. Items (e.g., "I worry too much over something that really doesn't matter", "I am content") are rated on a 4-point scale, such as from "Almost Never" to "Almost Always". Higher score to be a higher anxiety.	Day 1 pre-dose to Day 1 post-dose (pre-TSST-A)
Change in State-Trait Anxiety Inventory - State (STAI-S) During TSST-A (Trier Social Stress Test - Arithmetic) - Single Dose	Change in STAI-S score from pre-TSST-A to post-TSST-A at 0, 15, 25, and 55 minutes on Day 1. The scale assesses how participants feel "right-now". It measures subjective and temporary fluctuations in feelings associated with anxiety. Items (e.g., "I worry too much over something that really doesn't matter", "I am content") are rated on a 4-point scale, such as from "Almost Never" to "Almost Always". Higher score to be a worse outcome.	Day 1 assessments at pre-TSST-A, and post-TSST-A at 0, 15, 25, 55 minutes
Change in State-Trait Anxiety Inventory - State (STAI-S) - Multiple-Day Dosing	Change in STAI-S score from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 29 after a single dose. The scale assesses how participants feel "right-now". It measures subjective and temporary fluctuations in feelings associated with anxiety. Items (e.g., "I worry too much over something that really doesn't matter", "I am content") are rated on a 4-point scale, such as from "Almost Never" to "Almost Always". Higher score to be a worse outcome.	Day 29 pre-dose to Day 29 pre-TSST-A
Change in State-Trait Anxiety Inventory - State (STAI-S) During TSST-A (Trier Social Stress Test - Arithmetic) - Multiple-Day Dosing	Change in STAI-S score from pre-TSST-A to post-TSST-A at 0, 15, 25, and 55 minutes on Day 29. The scale assesses how participants feel "right-now". It measures subjective and temporary fluctuations in feelings associated with anxiety. Items (e.g., "I worry too much over something that really doesn't matter", "I am content") are rated on a 4-point scale, such as from "Almost Never" to "Almost Always". Higher score to be a worse outcome.	Day 29 measurements at pre-TSST-A, and post-TSST-A at 0, 15, 25 and 55 minutes.
Change in State-Trait Anxiety Inventory - Trait (STAI-T)	Change in STAI-T score from pre-dose Day 1 to pre-dose Day 29. The scale assesses how respondents feel "generally". It measures relatively stable individual differences in anxiety proneness. Items (e.g., "I worry too much over something that really doesn't matter", "I am content") are rated on a 4-point scale, such as from "Almost Never" to "Almost Always". Higher score to be a higher anxiety.	Day 1 to Day 29
Physiological Stress Markers (Cortisol) - Single Dose	Change in salivary cortisol (µg/dL) from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 1.	Day 1
Physiological Stress Markers (Alpha-Amylase) - Single Dose	Change in alpha-amylase (U/mL) from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 1	Day 1
Physiological Stress Markers (Cortisol) During Trier Social Stress Test - Arithmetic (TSST-A) - Single Dose	Change in salivary cortisol (µg/dL) from pre-TSST-A to 10, 20, 30, and 60 minutes post-TSST-A	Day 1
Physiological Stress Markers (Alpha-Amylase) During Trier Social Stress Test - Arithmetic (TSST-A) - Single Dose	Change in salivary alpha-amylase (U/mL) from pre-TSST-A to 10, 20, 30, and 60 minutes post-TSST-A	Day 1
Physiological Stress Markers (Heart Rate) During Trier Social Stress Test - Arithmetic (TSST-A) - Single Dose	Change in heart rate (bpm) from pre-TSST-A to 60 minutes post-TSST-A.	Day 1
Physiological Stress Markers (Cortisol) - Multiple-Day Dose	Change in salivary cortisol (µg/dL) from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 29.	Day 29
Physiological Stress Markers (Alpha-Amylase) - Multiple-Day Dose	Change in salivary alpha-amylase (U/mL) from pre-dose to post-dose (pre-Trier Social Stress Test - Arithmetic [pre-TSST-A]) on Day 29.	Day 29
Physiological Stress Markers (Cortisol) During Trier Social Stress Test - Arithmetic (TSST-A) - Multiple-Day Dosing	Change in salivary cortisol (µg/dL) from pre-TSST-A to 10, 20, 30, and 60 minutes post-TSST-A.	Day 29
Physiological Stress Markers (Alpha-Amylase) During Trier Social Stress Test - Arithmetic (TSST-A) - Multiple-Day Dosing	Change in salivary alpha-amylase (U/mL) from pre-TSST-A to 10, 20, 30, and 60 minutes post-TSST-A	Day 29
Physiological Stress Markers (Heart Rate) During Trier Social Stress Test - Arithmetic (TSST-A) - Multiple-Day Dosing	Change in heart rate (bpm) from pre-TSST-A to 60 minutes post-TSST-A.	Day 29
Awakening Cortisol Response	Change in morning awakening salivary cortisol over 30 minutes from baseline to Day 29.	Baseline Day 1 to Day 29
Awakening Alpha-Amylase Response	Change in morning awakening alpha-amylase over 30 minutes from baseline to Day 29	Baseline Day 1 to Day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Profile of Mitragynine AUC0-8 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 8 hours after a single dose.	Day 1 (0-8 hours)
PK Profile of Mitragynine AUC8-24 (Single Dose)	Area under the plasma concentration (AUC)-time curve from 8 to 24 hours after a single dose.	Day 1-Day 2 (8-24 hours)
PK Profile of Mitragynine AUC0-24 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 24 hours after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Mitragynine AUC0-∞ (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to infinity after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Mitragynine Cmax (Single Dose)	Maximum observed plasma concentration (Cmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Mitragynine Tmax (Single Dose)	Time to reach maximum observed plasma concentration (Tmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Mitragynine Half-Life (T½) (Single Dose)	Terminal elimination half-life after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Mitragynine Elimination Rate Constant (Kel) (Single Dose)	Terminal elimination rate constant after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine AUC0-8 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 8 hours after a single dose.	Day 1 (0-8 hours)
PK Profile of 7-hydroxymitragynine AUC8-24 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 8 to 24 hours after a single dose.	Day 1-Day 2 (8-24 hours)
PK Profile of 7-hydroxymitragynine AUC0-24 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 24 hours after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine AUC0-∞ (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to infinity after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine Cmax (Single Dose)	Maximum observed plasma concentration (Cmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine Tmax (Single Dose)	Time to reach maximum observed plasma concentration (Tmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine Half-Life (T½) (Single Dose)	Terminal elimination half-life after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of 7-hydroxymitragynine Elimination Rate Constant (Kel) (Single Dose)	Terminal elimination rate constant after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain AUC0-8 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 8 hours after a single dose.	Day 1 (0-8 hours)
PK Profile of Kavain AUC8-24 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 8 to 24 hours after a single dose.	Day 1-Day 2 (8-24 hours)
PK Profile of Kavain AUC0-24 (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to 24 hours after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain AUC0-∞ (Single Dose)	Area under the plasma concentration (AUC) -time curve from 0 to infinity after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain Cmax (Single Dose)	Maximum observed plasma concentration (Cmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain Tmax (Single Dose)	Time to reach maximum observed plasma concentration (Tmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain Half-Life (T½) (Single Dose)	Terminal elimination half-life after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Kavain Elimination Rate Constant (Kel) (Single Dose)	Terminal elimination rate constant after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain AUC0-8 (Single Dose)	Area under the plasma concentration (AUC) - time curve from 0 to 8 hours after a single dose.	Day 1 (0-8 hours)
PK Profile of Dihydrokavain AUC8-24 (Single Dose)	Area under the plasma concentration (AUC) - time curve from 8 to 24 hours after a single dose.	Day 1-Day 2 (8-24 hours)
PK Profile of Dihydrokavain AUC0-24 (Single Dose)	Area under the plasma concentration (AUC) - time curve from 0 to 24 hours after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain AUC0-∞ (Single Dose)	Area under the plasma concentration (AUC) - time curve from 0 to infinity after a single dose.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain Cmax (Single Dose)	Maximum observed plasma concentration (Cmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain Tmax (Single Dose)	Time to reach maximum observed plasma concentration (Tmax) after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain Half-Life (T½) (Single Dose)	Terminal elimination half-life after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile of Dihydrokavain Elimination Rate Constant (Kel) (Single Dose)	Terminal elimination rate constant after a single dose from 0 to 24 hours.	Day 1-Day 2 (0-24 hours)
PK Profile Mitragynine AUC0-8, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 8 hours at steady state after multiple-day dosing.	Day 29 (0-8 hours)
PK Profile Mitragynine AUC8-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 8 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (8-24 hours)
PK Profile Mitragynine AUC0-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Mitragynine AUC0-∞, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to infinity at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Mitragynine Cmax, Steady State (Multiple-Day Dose)	Maximum observed plasma concentration (Cmax) at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Mitragynine Tmax, Steady State (Multiple-Day Dose)	Time to reach maximum observed plasma concentration (Tmax) at steady state.	Day 29-30 (0-24 hours)
PK Profile Mitragynine Half-Life (T1/2) at Steady State (Multiple-Day Dose)	Terminal elimination half-life at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Mitragynine Elimination Rate Constant (Kel) at Steady State (Multiple-Day Dose)	Terminal elimination rate constant at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine AUC0-8, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 8 hours at steady state after multiple-day dosing.	Day 29 (0-8 hours)
PK Profile 7-hydroxymitragynine AUC8-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 8 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (8-24 hours)
PK Profile 7-hydroxymitragynine AUC0-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine AUC0-∞, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to infinity at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine Cmax, Steady State (Multiple-Day Dose)	Maximum observed plasma concentration (Cmax) at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine Tmax, Steady State (Multiple-Day Dose)	Time to reach maximum observed plasma concentration (Tmax) at steady state.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine Half-Life (T1/2) at Steady State (Multiple-Day Dose)	Terminal elimination half-life at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile 7-hydroxymitragynine Elimination Rate Constant (Kel) at Steady State (Multiple-Day Dose)	Terminal elimination rate constant at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Kavain AUC0-8, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 8 hours at steady state after multiple-day dosing.	Day 29 (0-8 hours)
PK Profile Kavain AUC8-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 8 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (8-24 hours)
PK Profile Kavain AUC0-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Kavain AUC0-∞, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to infinity at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Kavain Cmax, Steady State (Multiple-Day Dose)	Maximum observed plasma concentration (Cmax) at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Kavain Tmax, Steady State (Multiple-Day Dose)	Time to reach maximum observed plasma concentration (Tmax) at steady state.	Day 29-30 (0-24 hours)
PK Profile Kavain Half-Life (T1/2) at Steady State (Multiple-Day Dose)	Terminal elimination half-life at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Kavain Elimination Rate Constant (Kel) at Steady State (Multiple-Day Dose)	Terminal elimination rate constant at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain AUC0-8, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 8 hours at steady state after multiple-day dosing.	Day 29 (0-8 hours)
PK Profile Dihydrokavain AUC8-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 8 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (8-24 hours)
PK Profile Dihydrokavain AUC0-24, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to 24 hours at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain AUC0-∞, Steady State (Multiple-Day Dose)	Area under the plasma concentration (AUC)- time curve from 0 to infinity at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain Cmax, Steady State (Multiple-Day Dose)	Maximum observed plasma concentration (Cmax) at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain Tmax, Steady State (Multiple-Day Dose)	Time to reach maximum observed plasma concentration (Tmax) at steady state.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain Half-Life (T1/2) at Steady State (Multiple-Day Dose)	Terminal elimination half-life at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
PK Profile Dihydrokavain Elimination Rate Constant (Kel) at Steady State (Multiple-Day Dose)	Terminal elimination rate constant at steady state after multiple-day dosing.	Day 29-30 (0-24 hours)
Trough Plasma Concentrations Over Time	To measure trough plasma concentrations of kratom alkaloids and kavalactones during repeated twice-daily dosing, using pre-dose blood samples collected on alternate days over the first 14 days of study product use. This evaluates concentration buildup prior to steady-state attainment.	Days 1-15 (pre-dose trough sampling)
Comparison of Single-Dose vs Steady-State Cmax	Difference between between single-dose maximum observed plasma concentration (Cmax) on Day 1 and and steady-state Cmax at Day 29 to evaluate systemic accumulation.	Single dose: Day 1 and Day 2 (0-24 hours) Steady State: Day 29 and Day 30 (0-24 hours), Day 31 (48h), Day 36 (168h)
Comparison of Single-Dose vs Steady-State AUC0-8	Difference between single-dose area under the plasma concentration (AUC0-8) (Day 1) and steady-state AUC0-8 (Day 29) to assess accumulation over the first 8 hours.	Single dose: Day 1 and Day 2 (0-24 hours) Steady State: Day 29 and Day 30 (0-24 hours), Day 31 (48h), Day 36 (168h)
Comparison of Single-Dose vs Steady-State AUC0-24	Difference between single-dose area under the plasma concentration (AUC0-24) (Day 1 and Day 2) and steady-state AUC0-24 (Day 29 and Day 30) to assess the 24-hour exposure accumulation.	Single dose: Day 1 and Day 2 (0-24 hours) Steady State: Day 29 and Day 30 (0-24 hours), Day 31 (48h), Day 36 (168h)
Perception of Trier Social Stress Test - Arithmetic (TSST-A) Task	Perception of the task survey at completion of TSST-A on Days 1 and 29. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses the participants feeling of the TSST-A task. Higher scores indicate higher feelings of difficulty and stress.	Day 1 and Day 29
Modified Drug Effects Questionnaire (DEQ)	To assess the effect of TP on subjective drug effects compared to placebo. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses the participants subjective experience after consuming the TP.	Day 1 and Day 29, post-dose at 55, 85, 95, 110, 120, 150 minutes
Overall Well Being, Health, and Pain	To assess the effect of TP on overall well-being, health, and pain compared to placebo. 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.	Day 1 to Days 15, 29, 36
Product Reliance Scale	To assess the effect of TP on the severity of dependence compared to placebo. A non-validated questionnaire consisting of 3 questions assessing how dependent participants feel when taking TP. Questions are scored on a 5-point Likert scale, ranging from 0 ("Never") to 4 ("Very Often"). Higher scores indicate higher feelings of dependence.	Days 29, 31, 36
EMA Mood Assessments	To assess the effect of TP on mood compared to placebo. 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 4, 8, 12, 16, 20, 24, 28, 30, 32, 34
Study Product Perception & Attitude Survey	To assess the effect of TP on study product perceptions and attitudes compared to placebo. A non-validated questionnaire consisting of multiple items assessing participants' subjective experiences with the study product, including effects on daily functioning, energy, sleep, mood, stress/anxiety, focus, 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 15 and 29
Safety Assessment - Incidence of Treatment-Emergent Adverse Events	Number and percentage of participants experiencing treatment-emergent adverse events from first dose through follow-up.	Screening through Day 36 and follow-up phone call (approximately 8 weeks)
Safety Assessment - Vital Signs (Heart Rate)	Change in Heart Rate (beats per minute) from baseline to each study visit.	Screening through Day 36
Safety Assessment - Vital Signs (Blood Pressure)	Change in Blood Pressure (mmHg) from baseline to each study visit.	Screening through Day 36
Safety Assessment - Vital Signs (Respiratory Rate)	Change in Respiratory Rate (breaths per minute) from baseline to each study visit.	Screening through Day 36
Safety Assessment - Vital Signs (Oxygen Saturation)	Change in Oxygen Saturation (SpO₂ %) from baseline to each study visit.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Hemoglobin)	To assess the safety of TP through the change from baseline to each study visit in hemoglobin (g/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Hematocrit)	To assess the safety of TP through the change from baseline to each study visit in hematocrit (%).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - 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).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Red Cell Distribution Width)	To assess the safety of TP through the change from baseline to each study visit in red cell distribution width.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Mean Corpuscular Volume)	To assess the safety of TP through the change from baseline to each study visit in mean corpuscular volume (fL).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Mean Corpuscular Hemoglobin)	To assess the safety of TP through the change from baseline to each study visit in mean corpuscular hemoglobin (pg).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - 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).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - 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).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Neutrophil Count)	To assess the safety of TP through the change from baseline to each study visit in Neutrophil Count (×10^9/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Basophil Count)	To assess the safety of TP through the change from baseline to each study visit in basophil count (x 10^9/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Lymphocyte Count)	To assess the safety of TP through the change from baseline to each study visit in lymphocyte count (×10^9/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Monocyte Count)	To assess the safety of TP through the change from baseline to each study visit in hemoglobin (×10^9/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Platelet Count)	To assess the safety of TP through the change from baseline to each study visit in platelet count (×10^9/µL).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Mean Platelet Volume)	To assess the safety of TP through the change from baseline to each study visit in mean platelet volume (fL).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Hematology - Blood Smear Findings)	To assess the safety of TP through the change from baseline to each study visit in blood smear findings.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Blood Urea Nitrogen)	To assess the safety of TP through the change from baseline to each study visit in blood urea nitrogen (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Creatinine)	To assess the safety of TP through the change from baseline to each study visit in creatinine (umol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - 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).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Albumin)	To assess the safety of TP through the change from baseline to each study visit in albumin (g/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Random Glucose)	To assess the safety of TP through the change from baseline to each study visit in random glucose (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Fasting Glucose)	To assess the safety of TP through the change from baseline to each study visit in fasting glucose (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Total Protein)	To assess the safety of TP through the change from baseline to each study visit in total protein (g/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Sodium)	To assess the safety of TP through the change from baseline to each study visit in Sodium (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Potassium)	To assess the safety of TP through the change from baseline to each study visit in Potassium (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Clinical Chemistry - Chloride)	To assess the safety of TP through the change from baseline to each study visit in Chloride (mmol/L).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Aspartate Transaminase)	To assess the safety of TP through the change from baseline to each study visit in Aspartate Transaminase (AST) in U/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Alanine Transaminase)	To assess the safety of TP through the change from baseline to each study visit in Alanine Transaminase (ALT) in U/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - 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.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Total Bilirubin)	To assess the safety of TP through the change from baseline to each study visit in Total Bilirubin in µmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Direct Bilirubin)	To assess the safety of TP through the change from baseline to each study visit in Direct Bilirubin in µmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - 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.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Alkaline Phosphatase)	To assess the safety of TP through the change from baseline to each study visit in Alkaline Phosphatase (ALP) in U/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - Prothrombin Time)	To assess the safety of TP through the change from baseline to each study visit in Prothrombin Time (PT) in seconds.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Liver Function Test - International Normalized Ratio)	To assess the safety of TP through the change from baseline to each study visit in International Normalized Ratio (INR).	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Thyroid Function Test - Thyroid-Stimulating Hormone)	To assess the safety of TP through the change from baseline to each study visit in Thyroid-Stimulating Hormone (TSH) in mIU/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Thyroid Function Test - Triiodothyronine)	To assess the safety of TP through the change from baseline to each study visit in Triiodothyronine (T3) in nmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Thyroid Function Test - Thyroxine )	To assess the safety of TP through the change from baseline to each study visit in Thyroxine (T4) in ug/dL.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Lipid Panel - Total Cholesterol)	To assess the safety of TP through the change from baseline to each study visit in Total Cholesterol in mmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Lipid Panel - HDL)	To assess the safety of TP through the change from baseline to each study visit in high-density lipoprotein (HDL) cholesterol in mmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Lipid Panel - LDL)	To assess the safety of TP through the change from baseline to each study visit in low-density lipoprotein (LDL) cholesterol in mmol/L.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Lipid Panel - HDL:LDL Ratio)	To assess the safety of TP through the change from baseline to each study visit in HDL:LDL Ratio.	Screening through Day 36
Safety Assessment - Clinical Laboratory Test (Lipid Panel - Triglycerides)	To assess the safety of TP through the change from baseline to each study visit in Triglycerides in mmol/L.	Screening through Day 36
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, Day 29, and follow-up visits (Day 31 and Day 36)
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 29, and follow-up visits (Day 31 and Day 36)
Appraisal of Effects Survey	To assess participant-reported perceptions of the effects of the study product compared to placebo. 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, 6, 10, 14, 18, 22, and 26.
Safety Assessment - Clinical Laboratory Test (Hematology - Eosinophil Count)	To assess the safety of TP through the change from baseline to each study visit in eosinophil count (×10^9/L).	Screening through Day 36

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): March 7, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 14, 2026

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Anxiety; Relaxation; Stress Control
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: B05-25-02-T0083

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