Largest Controlled Kratom Safety Study Finds Acceptable Profile, No Serious Adverse Events at Tested Doses

Why it matters

This is the first controlled multiple-dose study of kratom powder in humans and the largest kratom safety study to date, providing peer-reviewed clinical data at a time when regulators and lawmakers are debating how to classify botanical kratom. The findings give clinicians and policymakers evidence to distinguish botanical kratom's safety profile from that of concentrated 7-OH products.

The big picture

Debate over kratom's safety has long been hampered by a near-total absence of controlled human trials. Most prior concerns derived from case reports, poison-center data, and animal studies. This randomized, double-blind, placebo-controlled trial by Huestis and colleagues fills a critical evidence gap. Sponsored by NP Pharma—a conflict of interest the authors disclose—the study used a well-characterized commercial kratom powder (MitraLeaf) tested across four escalating doses in 116 healthy volunteers over 47 days.

Key findings

• 116 participants received MitraLeaf kratom powder (500–4000 mg, delivering 6.65–53.2 mg mitragynine) or placebo across single and 15 daily doses with 23-day follow-up
• No serious adverse events or deaths were reported in any active-drug cohort
• Most treatment-emergent adverse events were mild; common events included dizziness, nausea, headache, and feeling hot—generally increasing with dose
• Some liver enzyme (ALT/AST) elevations occurred at the highest dose; none met FDA's Hy's Law criteria for serious drug-induced liver injury
• Abuse potential was low—euphoric mood reported by just 3 participants (1 active, 1 active, 1 placebo); only 1 mild withdrawal symptom (diarrhea) recorded during follow-up
• The 7-OH/mitragynine concentration ratio (0.15–0.31) in plasma was consistent with normal hepatic metabolism of botanical kratom, not the higher ratios seen with synthetic 7-OH products

What they say

"This novel single- and multiple-dose randomized, placebo-controlled, double-blind 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." — Marilyn A. Huestis, PhD, et al., Therapeutic Drug Monitoring, 2026

Bottom line

The largest controlled human kratom study to date found no serious adverse events, minimal abuse potential, and no drug-induced liver injury meeting established criteria at typical use doses—though liver enzyme monitoring is recommended and industry funding is a noted limitation.