Kratom is increasingly used in the United States for energy and self-management of pain and mood. While its active alkaloid, mitragynine, has partial μ-opioid receptor agonist activity, clinical data on its abuse potential remain limited. This study evaluated abuse-related outcomes following single and multiple doses of dried kratom leaf powder in healthy kratom-naive adults in a randomized, double-blind, placebo-controlled study. Healthy participants (n = 116) received a single oral dose or 15 consecutive daily doses of Mitra-Leaf kratom capsules (4 cohorts: 500-4000 mg dried leaf powder; equivalent to 6.65-53.2 mg mitragynine; n = 12-13 per cohort, n = 49 total) or placebo (n = 67). Subjective effects were assessed using the Drug Effects Questionnaire (DEQ). Opioid withdrawal symptoms were evaluated using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale (COWS). Abuse-related treatment-emergent adverse events (ARTEAEs) were recorded. DEQ responses were dose-related, except between the middle two dose levels with statistically significant increases in maximum effect and area-under-the-curve compared to placebo observed only at the highest single dose. DEQ responses decreased following repeated dosing. No participants met the threshold for clinically meaningful opioid withdrawal based on COWS or SOWS. ARTEAEs occurred more frequently at higher doses but were generally mild and resolved without sequelae. No serious adverse events or deaths were reported. Oral administration of kratom at tested doses was well tolerated and associated with modest, dose-related subjective effects, minimal withdrawal symptoms, and low ARTEAE rates. Findings support further research on kratom's safety and therapeutic potential, while emphasizing the importance of dose control and product standardization.
Coe et al. (Sun,) studied this question.