Kratom-Induced Liver Injury and CYP-Mediated Drug Interaction: New Case Report from Cureus

Why it matters

Clinicians face a growing challenge: patients using kratom may develop silent liver damage and dangerous interactions with prescription medications metabolized by the liver's CYP enzyme system, including common antidepressants. This case shows the risks can occur even with raw-leaf kratom at moderate doses.

The big picture

Kratom is used by millions of Americans for pain, anxiety, and opioid withdrawal, often without informing their doctors. Studies and systematic reviews have documented rising cases of kratom-induced liver injury (KILI), ranging from mild enzyme elevations to acute liver failure. As commercial products become more concentrated, the risk of hepatotoxicity and drug-drug interactions is expected to increase.

Key findings

• A 45-year-old male using raw kratom leaf daily for 5-6 years developed mildly elevated liver enzymes (ALT 70 U/L, GGT 141 U/L) and supratherapeutic nortriptyline levels
• All laboratory values normalized within 3 weeks of kratom discontinuation, confirming kratom as the causative agent
• Mitragynine inhibits CYP2D6 and CYP3A4 enzymes that metabolize nortriptyline and hundreds of other prescription drugs
• Concentrated kratom products likely carry higher hepatotoxic and pharmacokinetic risk than raw leaf
• Systematic reviews have identified 69 published cases of kratom-induced liver injury, 80% showing cholestatic patterns

What they say

Even mild liver enzyme elevations in patients using kratom warrant evaluation, particularly with concurrent CYP-metabolized medications. Clinicians should educate patients about product variability, monitor liver function and drug levels, and consider temporary kratom discontinuation to assess causality. - Gnanasegaram & Stanciu, Cureus, 2026

Bottom line

Kratom can silently elevate liver enzymes and cause dangerous prescription drug interactions - clinicians must ask about kratom use in every patient on CYP-metabolized medications.