Real-world Momentary Assessment of Kratom Use Accompanied by Product Assays: A Natural-history Study for Interdisciplinary Characterization of Kratom Use and Pharmacology

Study Description:

Our natural-history study will build on preliminary research on the use and effects of kratom. We propose to examine momentary reasons for and self-reported effects of kratom-product use in daily life, associations of these findings with product alkaloid content and, in a direct-observation setting, externally observable effects of kratom-product use.

In the Main EMA Study, to be conducted nationwide via online/mobile data collection, we will examine instances of kratom use in naturalistic settings using EMA, and we will characterize the alkaloid content of the products used. The target sample size is 240 completers.

In the In-person Substudy, 10 participants who reside near the NIDA IRP will conduct the same activities as in the Main EMA Study (online questionnaires, then EMA for 15 days), plus a one-day outpatient session. On the session day, we will collect physiological and task-derived measures (these will include a driving-simulation task) after the participants have taken their regular kratom product dose. This will be followed by semi-structured narrative qualitative interviews.

Objectives for the Main EMA Study:

Primary objective: to collect momentary assessments of individual instances of kratom use and effects associated with use (e.g., sleep duration, mood, motivations for use, acute effects, etc.) in daily life over 15 days among regular kratom users, for better understanding kratom use in real-world contexts and in real time.

Secondary objective: to determine associations of momentary responses with directly assayed content of samples of participants kratom products.

Exploratory objectives: to evaluate whether retrospective self-report on cross-sectional questionnaires completed prior to EMA correlate with momentary self-report (e.g., do people who report using kratom primarily for pain actually report self-treatment of pain symptoms as a proximal motivation?). A second exploratory objective is to determine whether there are subgroups of participants who share distinct patterns of kratom use.

Objectives for the In-Person Substudy:

Primary objective: to evaluate the relationships among subjective self-reported kratom effects (measured over 3 hours post-dosing), the kratom product used, and kratom alkaloid concentrations in biospecimens.

Secondary objective: to gather comprehensive narrative case-report data via qualitative interviewing.

Exploratory objectives include: First, to assess vital signs, pupil size, and psychomotor performance of participants prior to their taking their regular kratom dose and at repeated intervals subsequent to their taking their regular kratom product dose (4-6 total time points). Second, to measure signs of opioid withdrawal among participants prior to their taking their regular kratom dose and after (4 total time points). Third, to measure participants performance on a driving simulation before they have taken their kratom dose and after they have taken their kratom dose (2 time points total).

Endpoints for Main EMA Study:

For primary objectives: proximal motivations for use; somatic and psychoactive effects reported from use; associations between self-reported states (e.g., mood, pain, craving), and particular kratom product types reported as being used; associations between self-reported states (e.g., mood, pain, craving) and kratom dose.

For secondary objectives: quantification of up to 14 kratom alkaloids; differences in alkaloid content by kratom product type (e.g., extract, raw plant matter); differences in alkaloid content by kratom vendor type (e.g., small online vendor, large-scale importer and distributor; between-person correlations (self-reported momentary effects and alkaloid levels).

For exploratory objectives: correlation of cross-sectional self-reported kratom use motivations and momentary (proximate) kratom use motivations; Cluster analysis of kratom use patterns.

Endpoints for In-person Substudy:

For primary objectives: Concentrations of detectable kratom alkaloids and their metabolites in human plasma and urine; differences in concentrations by kratom product type (e.g., extract, raw plant matter); Addiction Research Center Inventory and other self-report questionnaires.

For secondary objective: narrative case report series documenting participant s kratom use, from initiation to present day.

For exploratory objectives: Psychomotor performance; Resting vitals; Pupil size; Subjective Opioid Withdrawal Scale; Driving-simulation performance.

• INCLUSION CRITERIA:

For the Main EMA Study

• Regular kratom use.
• Passing data validity checks on the online screening questionnaire.
• Reporting ownership of a smartphone.
• Age >= 18 years.
• Currently residing in the US .
• Willingness to complete all study activities as described in the online study preamble and informed consent, including willingness to provide a small sample of their kratom product.
• Passing online Main Study consent quiz with at least 8/10 correct answers.
• English language proficiency.
• Not incarcerated.

Additional inclusion criterion for the In-person Substudy:

-Residing in or near MD.

Exclusion criteria

For the Main EMA Study

• Missing data validity checks on screening questionnaire
• Decisionally impaired adults..

Additional exclusion criterion for the In-person Substudy:

• Pregnancy by urine test.
• Self-reported proneness to experiencing motion sickness or feelings of vertigo. This is a precaution, because motion sickness could interfere with the task or cause discomfort.