Pilot Dose-Finding Trial Finds No Serious Adverse Events Up to 12 Grams of Botanical Kratom

Why it matters

This is a controlled, dose-escalation human trial, rare for kratom, that gives clinicians and regulators actual safety data across a dose range rather than relying on self-reported use or poison-center reports.

The big picture

The trial used single-sourced botanical kratom with trace 7-OH levels representative of typical leaf products, distinguishing its findings from concentrated or synthetic derivatives now facing federal scheduling. Its authors, including FDA and University of Florida researchers, caution the results may not generalize to other kratom-containing products on the market.

Key findings

• 40 recreational polydrug users with opioid experience received single doses of placebo or kratom from 1 g up to 12 g in a double-blind, between-subjects design
• No deaths or serious adverse events occurred at any dose tested
• Somnolence, vomiting, and nausea were the most common adverse events reported
• Doses of 3 grams or more produced pupillary constriction, an opioid-like effect
• The 12 gram dose increased subjective "drug liking" ratings and other measures associated with abuse potential
• Kratom alkaloid blood concentrations showed generally orderly, dose-related patterns

What they say

The study authors conclude that "kratom produced some opioid-like effects including pupillary constriction, and the 12 g dose produced effects commonly associated with drugs of abuse," while cautioning that results reflect only the single-sourced botanical product tested.

Bottom line

**In this controlled trial, botanical kratom caused no serious adverse events up to 12 grams, but the highest dose produced measurable opioid-like and abuse-associated effects.**