Pharmacokinetics of Kava and Kratom Alone and in Combination

N/AActive Not RecruitingNCT07583407

Botanic Tonics, LLC18 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Herb-Herb Interaction Pharmacokinetics

Interventions

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)

Eligibility

Sex: ALLMin age: 21 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

ApexTrials

Guelph, Ontario, Canada

Outcomes

Primary Outcomes

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

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcomes

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

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

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

Maximum Observed Plasma Concentration (Cmax) for Kavain

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

Data from ClinicalTrials.gov

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Time frame: 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

Time frame: 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

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

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

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

Maximum Observed Plasma Concentration (Cmax) for Dihydrokavain

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

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

Time to Maximum Plasma Concentration (Tmax) for Dihydrokavain

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

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

Terminal Elimination Half-Life (T½) for Dihydrokavain

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

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

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

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

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

Maximum Observed Plasma Concentration (Cmax) for Mitragynine

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

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

Time to Maximum Plasma Concentration (Tmax) for Mitragynine

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

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

Terminal Elimination Half-Life (T½) for Mitragynine

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

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

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

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

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

Maximum Observed Plasma Concentration (Cmax) for 7-Hydroxymitragynine

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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