Direct Observation Study of Kratom Product Effects Among Regular Consumers

Study Overview
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Brief Summary
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The goal of this observational clinical study is to is to learn more about how commercial kratom products affect healthy adults who consume them regularly. The main questions it aims to answer are: What are the acute physiological, subjective, and cognitive effects of kratom following participant self-administration of a single oral dose of the participants usual kratom product at the participants typical dose? What are the physiological, subjective, and cognitive effects associated with kratom product discontinuation among adults who use regularly? What are the pharmacokinetics of kratom products consumed by adults who use regularly? On the first study day: Under direct observation, participants will self-administer a single oral dose of the participants own commercial kratom product that that is regularly taken and will consume it at the participants self-selected typical dose/serving. Following this, serial blood draws and urine collection will occur along with administration of validated questionnaires, tests, and continual monitoring. After this first study day, participants will no longer be permitted to use any of the participants kratom product during the study. On study nights/days 2-3: participants will reside a clinical research unit and be observed and evaluated for kratom withdrawal syndrome.

Official Title
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Observing the Acute Effects Following a Single Oral Dose of Kratom and Effects Following Kratom Cessation Among Adults Who Use Regularly.

Conditions
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Withdrawal Symptoms

Intervention / Treatment
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* Behavioral: Effects from acute kratom exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years; Regularly uses kratom; English language proficient; Willingness to provide requested samples of the kratom product they are currently taking. Exclusion Criteria: Current physical dependence or urine drug screen for substances prohibited for use in this study; Currently pregnant or breastfeeding; Physical, psychiatric, environmental, or situational condition considered by the study team to increase risk or undue burden. Note: additional blinded criteria to be provided upon study completion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute kratom exposure<br>Participants who regularly consume kratom will orally self-administer a single serving of the participants commercial kratom product under direct observation in order to evaluate acute physiological, subjective, and cognitive effects and determine pharmacokinetics. This will occur during the first 24 hours of study participation. Participants will undergo direct observation and assessment for after ceasing all kratom product use. Physiological, subjective, and cognitive effects during this supervised withdrawal will be assessed. | Behavioral: Effects from acute kratom exposure<br>* Participants who regularly use commercial Kratom products will orally consume a known quantity of kratom under direct observation on first study day; following this, participants will stop kratom use for approximately 2 nights and 2.5 days for the duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak subjective opioid withdrawal score | Peak score on the Subjective Opioid Withdrawal Scale (SOWS); that occurs between Study Days 1-3. Score range 0-64. 5-point scale of intensity: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. Higher score indicates higher intensity. SOWS will be administered at 8 time points on Study Days 1-2 and 7 time points on Study Day 3. | Up to 3 days | 
| Time in minutes until a Subjective Opioid Withdrawal (SOWS) score of more than 11 is reached | Time, in minutes, until at least a moderate score (of 11 or higher) is reached on the Subjective Opioid Withdrawal Scale (SOWS). SOWS will be administered at 8 time points on Study Days 1-2 and 7 time points on Study Day 3. 5-point scale of intensity: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. Score range 0-64. Higher score indicates higher intensity. | up to 3 days | 
| Peak rating and changes in rating on Drug Effects Questionnaire (primary subjective outcome) | Drug Effects Questionnaire (DEQ) visual analogue scale (0-100) rating for DEQ item feeling high. The DEQ will be administered at 7 timepoints on Study Day 1 and at 6 times points on Study Days 2 and 3. | Up to 3 days | 
| Peak rating and change in rating on Drug Effects Questionnaire (primary subjective outcome) | Drug Effects Questionnaire (DEQ) visual analogue scale (0-100) rating for DEQ item drug liking. The DEQ will be administered at 7 time points on Study Day 1 and at 6 times points on Study Days 2 and 3. | Up to 3 days | 
| Changes in accuracy on psychomotor task (primary cognitive outcome) | The 2-minute computerized Digit Symbol Substitution Task (DSST) outcome of total number of correct responses (accuracy) within the 2-minute test window. This will evaluate cognitive performance and impairment. The DSST will be administered at 7 time points on Study Day 1 and at 6 times points on Study Days 2 and 3. | Up to 3 days | 
| Pupil diameter nadir size as measured in millimeters (mm) (primary physiological outcome). | Pupil diameter in mm under stable light conditions using a pupilometer. Pupil size will be measured at 8 timepoints on Study Days 1 and 2 and at 7 timepoints on Study Day 3 | Up to 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kratom, pharmacokinetics, pharmacodynamics