Abstract
BACKGROUND AND AIMS: Using ecological momentary assessment (EMA), we undertook a natural experiment wherein kratom-product variability was a tool to assess kratom dose-response relationships based on product form and alkaloid level. METHODS: Between July-November 2022, 357 US kratom consumers (56.6 % male, 90.2 % non-Hispanic white) completed 15 days of EMA; 348 participants submitted samples of the products used most often during EMA. These were assayed for ten alkaloids using ultra-performance liquid chromatography-tandem mass spectrometry. Self-reported kratom effects were modeled as a function of kratom amount and alkaloid content. RESULTS: Participants used over 220 brands. The most-reported product forms were loose powder (55.8 %) and encapsulated powder (26.8 %); extracts were used less (419 uses across 9.48 % of participants). Of the 12,244 use-event entries, 7726 had follow-up data (15-180minutes after use) on felt effects. Effects were stronger in participants with a higher average amount per use. Within-person dose-response relationships were obscured by highly-consistent within-person dosages. Effects of loose powder decreased over three hours; effects of extracts started higher but decreased more rapidly. Dose-response relationships for specific alkaloids could not be reliably established because total alkaloid content and relative levels of specific alkaloids showed limited variability between products. Higher levels of corynoxine alkaloids were associated with slightly stronger effects, possibly an artifact of modeling data with low alkaloid variability. CONCLUSIONS: Alkaloid content was surprisingly consistent across kratom products, and participants were consistent in the amount they used across events. Firm conclusions about alkaloid-effect relationships for kratom will require experimenter-controlled manipulations of agent and dose.