Direct Observation Study of Kratom Product Effects Among Regular Consumers

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

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:

1. 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?
2. What are the physiological, subjective, and cognitive effects associated with kratom product discontinuation among adults who use regularly?
3. 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.

Study Overview

• Status: Recruiting
• Conditions: Kratom Pharmacokinetics; Kratom Pharmacodynamics; Kratom
• Intervention / Treatment: Behavioral: Effects from acute kratom exposure

• Study Type: Observational
• Enrollment (Estimated): 22

Contacts and Locations

• Study Contact: Name: Kirsten E Smith, Ph.D.; Phone Number: 865-418-8177; Email: ksmit398@jh.edu
• Study Contact Backup: Name: Naftali Zeilinger, B.A.; Phone Number: 410-550-0490; Email: nzeilin1@jh.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins University
      • Contact: Kirsten E Smith, Ph.D.; Phone Number: 865-418-8177; Email: ksmit398@jh.edu
      • Principal Investigator: Kirsten E Smith, Ph.D.
      • Contact: Naftali Zeilinger, B.A.; Phone Number: (410) 870-9227; Email: nzeilin1@jh.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults aged 21 or older who use kratom.

Description

INCLUSION CRITERIA:

1. >21 years
2. reporting kratom use >5 times per week for >3 months prior to study screening
3. English language proficiency
4. Willingness to provide requested samples of the kratom product being currently taken

EXCLUSION CRITERIA:

1. Reports any acute adverse, unexpected, or otherwise sudden health event related to the typical kratom product dose that occurred within 30 days of screening
2. Having ever sought medical attention for an acute adverse health event as a result of taking any kratom product.
3. Cannot or will not provide kratom product samples in the form of an unopened package of kratom that is clearly labeled with at least the product and vendor name.
4. Self-reports using kratom products by any other route than orally swallowing.
5. Current physical dependence on alcohol, benzodiazepines, or opioids
6. Reports use of fentanyl within the past month and/or has a fentanyl positive drug screen.
7. Discordance between self-reported substance use and drug screen results obtained during screening.
8. Lifetime or current psychotic disorder
9. Current untreated major depressive or bipolar disorder
10. Pregnancy or nursing
11. Physical, psychiatric, or environmental conditions considered by study team to increase risk or undue burden (e.g., untreated hypertension, high BMI, etc.).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Acute kratom exposure; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA); University of Florida
• Investigators: Principal Investigator: Kirsten E Smith, Ph.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: October 12, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: kratom
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome
• Other Study ID Numbers: IRB00408134; R00DA055571 (U.S. NIH Grant/Contract)

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