Largest Randomized Trial Finds Kratom Leaf Powder Safe and Well-Tolerated, With No Serious Adverse Events in 116 Volunteers

Why it matters

This is the largest and most rigorous controlled human study of kratom to date, providing critical safety data that regulators, clinicians, and policymakers need as legislative debates heat up across the country.

The big picture

Kratom is used by an estimated 2–5 million Americans, yet formal safety data from controlled human trials has been scarce. Regulators have often cited a lack of clinical evidence when evaluating kratom's risk profile. This randomized, double-blind, placebo-controlled study adds the most comprehensive human safety dataset for kratom published to date.

Key findings

• No serious adverse events or deaths were recorded across all 49 active-treatment participants
• The most common side effects were nausea, dizziness, and headache — all mild in the vast majority of cases
• Liver enzyme (ALT/AST) elevations occurred at the highest dose but did not meet FDA criteria for drug-induced liver injury
• No meaningful abuse potential was detected; euphoric mood was reported by only 1 participant receiving active drug
• No significant withdrawal symptoms emerged during the 23-day post-treatment monitoring period

What they say

"This SD and first MD controlled study shows that Mitragyna speciosa–derived MitraLeaf kratom powder was safe and well tolerated at the dose ranges tested, with no evidence of meaningful abuse potential or withdrawal." — Huestis et al., Therapeutic Drug Monitoring, 2026

Bottom line

The largest controlled human trial of kratom to date found it safe and well-tolerated at commonly consumed doses, though liver enzyme monitoring at higher doses is warranted in future studies.