Lab Study: Kratom Alkaloids Inhibit Key Liver Enzymes, But Plasma Levels in Humans Too Low to Cause Significant Drug Interactions

Why it matters

Drug interactions are a core safety concern for kratom users who take prescription medications. This study provides the first detailed look at how kratom's two main alkaloids affect UGT enzymes — a class of liver metabolizing enzymes distinct from the CYP450 enzymes more commonly studied — and concludes that normal human exposure levels are unlikely to produce clinically significant interactions via this specific pathway.

The big picture

Kratom contains over 40 alkaloids, and its potential to interfere with drug metabolism has been an area of growing scientific concern, particularly as users often take kratom alongside prescription medications. Prior research has focused mainly on CYP450 enzymes. This study extends that work to UDP-glucuronosyltransferases (UGTs), which are responsible for metabolizing many drugs including acetaminophen, ibuprofen, certain antiretrovirals, and some antidepressants.

Key findings

• Mitragynine showed strongest inhibition of UGT1A3 (IC50 of 72 µM) and moderate inhibition of UGT1A6, UGT1A9, and UGT2B15
• 7-Hydroxymitragynine showed strongest inhibition of UGT1A9 (IC50 of 51 µM)
• Kinetic analysis confirmed mitragynine uses noncompetitive inhibition on UGT1A3 and competitive inhibition on UGT1A9
• Crucially, the inhibitory concentrations (Ki values) found in the lab are far higher than peak plasma concentrations observed in human studies, suggesting no clinically relevant UGT-mediated drug interactions at typical kratom doses
• The study was conducted using recombinant human UGT enzymes and the standard probe substrate 4-methylumbelliferone

What they say

According to author Verawan Uchaipichat, "the experimental Ki values found here are relatively high compared to the maximum plasma concentrations of mitragynine and 7-hydroxymitragynine reported in humans, suggesting an unlikely potential for herb-drug interactions via UGT inhibition."

Bottom line

Kratom's main alkaloids inhibit UGT liver enzymes in the lab, but only at concentrations that are far higher than what humans actually absorb — suggesting UGT-mediated drug interactions are unlikely at normal kratom doses.