Herb-Herb InteractionNCT07583407
Pharmacokinetics of Kava and Kratom Alone and in Combination
A study testing Kava and Kratom Herbal Supplement, Kava Herbal Supplement and Kratom Herbal Supplement in people with Herb-Herb Interaction and Pharmacokinetics, run by Botanic Tonics, LLC at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Herb-Herb Interaction, Pharmacokinetics
- What is being tested?
- Kava and Kratom Herbal Supplement, Kava Herbal Supplement and Kratom Herbal Supplement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteCanada
- Study dates
- 4 May 2026to 20 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults who are between 21 - 55 years of age (inclusive) at the time of signing the informed consent.
- 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).
- Are able to consume the study product completely within the specified timeframe.
- 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.
- Have a BMI range of 18.5 - 29.9 kg/m2 at screening and Visit 2.
- Agree to follow the restrictions on concomitant treatments.
Show all 18Show fewer
- Agree to follow the restrictions on lifestyle.
- 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)
- 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.
- 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.
- 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.
- Agree to abstain from alcohol consumption for 48 hours prior to, and for the entire duration of, each treatment period.
- 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.
- Must have suitable veins for repeated venipuncture.
- Willing and able to attend video conference calls with study coordinators.
- Agrees not to donate blood until 3 months after study completion.
Who cannot join
- Individuals who are lactating, planning to become pregnant during the study, or pregnant as confirmed by a positive pregnancy test during study visits.
- Have a known sensitivity, intolerability, or allergy to any of the study products, their excipients, or rescue medication.
- 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.
- Have abnormal respiratory rate (RR) or SpO2 measurements at Screening or Baseline at the discretion of the investigator.
- 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.
- 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.
Show all 28Show fewer
- Demonstrates a positive screen for HIV at screening.
- Is currently enrolled in another clinical trial or has received/used an investigational product in another research study within 28 days before Visit 2.
- 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.
- Have been diagnosed with Type I/Type II diabetes or thyroid disease
- High BP at the Screening Visit or Visit 2 (≥140 systolic or ≥90 diastolic mmHg)
- Have low BP (<90 systolic or <60 diastolic mmHg) at Baseline unless deemed clinically insignificant by the investigator and the participant is asymptomatic.
- 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.
- Have known genetic polymorphisms of CYP450 enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2B6, and/or CYP3A4.
- 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.
- 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.
- 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.
- 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).
- 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.
- Reports donating plasma (e.g., plasmapheresis) within 15 days before Visit 2.
- Major surgery in 3 months before screening or planned major surgery during the study.
- History of alcohol or substance abuse (e.g., opioids, kratom) (including having been hospitalized for such an in-patient or out-patient intervention program).
- Evidence of addictive tendency as indicated by an LDQ score ≥21.
- Use of anxiolytic or sleep aids (natural health products or drugs) in the 4 weeks before Visit 2.
- 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.
- Excessive caffeine intake, defined as habitual consumption of >500 mg per day.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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.
- Conditions
- Herb-Herb Interaction, Pharmacokinetics
- Being tested
- Kava and Kratom Herbal Supplement, Kava Herbal Supplement, Kratom Herbal Supplement
- Keywords
- Kava, Kratom, Pharmacokinetics, Healthy Adults, Herbal Supplement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kava and Kratom Herbal SupplementDietary supplement
Half- Strength Feel Free Classic Tonic (TP1)
Kava Herbal SupplementDietary supplement
Kava Only Variant - Feel Free Tonic (TP2)
Kratom Herbal SupplementDietary supplement
Kratom Only Variant - Feel Free Tonic (TP3)
| Study group | Role | What they receive |
|---|---|---|
| Half- Strength Feel Free Classic Tonic (TP1) | Active comparator | Active Product of 380 mg Kava root extract and 1480 mg of dried Kratom Leaf powder per bottle Receives: Dietary Supplement: Kava and Kratom Herbal Supplement |
| Kava Only Variant - Feel Free Tonic (TP2) | Active comparator | Active Product of 380 mg Kava root extract per bottle Receives: Dietary Supplement: Kava Herbal Supplement |
| Kratom Only Variant - Feel Free Tonic (TP3) | Active comparator | Active Product of 1480 mg dried Kratom Leaf powder per bottle Receives: Dietary Supplement: Kratom Herbal Supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
Secondary outcomes (48)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: Day 14 of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2026
- Study start4 May 2026
- Primary completion20 Nov 2026 (estimated)
- Study completion20 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Herb-Herb InteractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Botanic Tonics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
- Responsible party
- Sponsor
- Investigators
- Ramsey Atallah, Study director, Botanic Tonics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07583407
- Sponsor's protocol ID
- B05-25-04-T0091
- Status last verified
- Sep 2026
- First submitted
- 4 May 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07583407
- Acronym / sponsor ID
- B05-25-04-T0091
- Conditions
- Herb-Herb Interaction, Pharmacokinetics
- Keywords
- Kava, Kratom, Pharmacokinetics, Healthy Adults, Herbal Supplement
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Botanic Tonics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
- Study start
- 4 May 2026 (actual)
- Primary completion
- 20 Nov 2026 (estimated)
- Study completion
- 20 Nov 2026 (estimated)
- First posted
- 13 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Half- Strength Feel Free Classic Tonic (TP1) | Active comparator | Dietary Supplement: Kava and Kratom Herbal SupplementActive Product of 380 mg Kava root extract and 1480 mg of dried Kratom Leaf powder per bottle |
| Kava Only Variant - Feel Free Tonic (TP2) | Active comparator | Dietary Supplement: Kava Herbal SupplementActive Product of 380 mg Kava root extract per bottle |
| Kratom Only Variant - Feel Free Tonic (TP3) | Active comparator | Dietary Supplement: Kratom Herbal SupplementActive Product of 1480 mg dried Kratom Leaf powder per bottle |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Adults who are between 21 - 55 years of age (inclusive) at the time of signing the informed consent.
- 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).
- Are able to consume the study product completely within the specified timeframe.
- 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.
- Have a BMI range of 18.5 - 29.9 kg/m2 at screening and Visit 2.
Key exclusion criteria (28 listed)
- Individuals who are lactating, planning to become pregnant during the study, or pregnant as confirmed by a positive pregnancy test during study visits.
- Have a known sensitivity, intolerability, or allergy to any of the study products, their excipients, or rescue medication.
- 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.
- Have abnormal respiratory rate (RR) or SpO2 measurements at Screening or Baseline at the discretion of the investigator.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Kava and Kratom Herbal SupplementHalf- Strength Feel Free Classic Tonic (TP1) | Dietary supplement | Half- Strength Feel Free Classic Tonic (TP1) |
| Kava Herbal SupplementKava Only Variant - Feel Free Tonic (TP2) | Dietary supplement | Kava Only Variant - Feel Free Tonic (TP2) |
| Kratom Herbal SupplementKratom Only Variant - Feel Free Tonic (TP3) | Dietary supplement | Kratom Only Variant - Feel Free Tonic (TP3) |
Primary outcome
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Kavain
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
AUC0-24 for kavain following single-dose administration of Kava alone or combined Kava and Kratom
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Dihydrokavain
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
AUC0-24 for dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Mitragynine
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
AUC0-24 for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for 7-Hydroxymitragynine
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
AUC0-24 for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom
48 secondary outcomes
Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Kavain
Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Kavain
Time frame: Day 1 of each treatment period (0-12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) for Kavain
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
Terminal Elimination Half-Life (T½) for Kavain
Time frame: 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
Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Dihydrokavain
Time frame: Day 1 of each treatment period (0-12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) for Dihydrokavain
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
Terminal Elimination Half-Life (T½) for Dihydrokavain
Time frame: 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
Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for Mitragynine
Time frame: Day 1 of each treatment period (0-12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) for Mitragynine
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
Terminal Elimination Half-Life (T½) for Mitragynine
Time frame: 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
Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) for 7-Hydroxymitragynine
Time frame: Day 1 of each treatment period (0-12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) for 7-Hydroxymitragynine
Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)
Terminal Elimination Half-Life (T½) for 7-Hydroxymitragynine
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Day 14 of each treatment period
Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Kavain
Time frame: Day 14 of each treatment period
Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Kavain
Time frame: Day 14 of each treatment period
Terminal Elimination Half-Life at Steady State (T½,ss) for Kavain
Time frame: Day 14 of each treatment period
Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Kavain
Time frame: 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
Time frame: Day 14 of each treatment period
Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Dihydrokavain
Time frame: Day 14 of each treatment period
Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Dihydrokavain
Time frame: Day 14 of each treatment period
Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Dihydrokavain
Time frame: Day 14 of each treatment period
Terminal Elimination Half-Life at Steady State (T½,ss) for Dihydrokavain
Time frame: Day 14 of each treatment period
Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Dihydrokavain
Time frame: 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
Time frame: Day 14 of each treatment period
Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Mitragynine
Time frame: Day 14 of each treatment period
Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Mitragynine
Time frame: Day 14 of each treatment period
Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Mitragynine
Time frame: Day 14 of each treatment period
Terminal Elimination Half-Life at Steady State (T½,ss) for Mitragynine
Time frame: Day 14 of each treatment period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Herb-Herb Interaction
RecruitingObservational study
Developing a Methodological Framework and a Dissemination Plan for Herb-drug Interactions-related Clinical Practice Guidelines
Herb-drug Interactions
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramsey Atallah study director
Botanic Tonics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Kava and Kratom Herbal Supplement, Kava Herbal Supplement and Kratom Herbal Supplement in people with Herb-Herb Interaction and Pharmacokinetics, run by Botanic Tonics, LLC at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Kavain (time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.