Kratom Shows Promise for Opioid Use Disorder but Critical Safety Gaps Remain

Why it matters

Leading kratom researchers at the University of Florida outline both the extraordinary therapeutic potential and the serious safety challenges that must be resolved before kratom can be formally used to treat opioid use disorder.

The big picture

As the opioid crisis deepens, kratom's dual identity — natural OUD remedy and unregulated commercial product — creates a critical challenge for medicine; this editorial calls for urgently needed clinical trials and standardization.

Key findings

• • Mitragynine is a biased, partial mu-opioid receptor agonist that activates G-proteins without recruiting beta-arrestin-2 — the mechanism believed to reduce respiratory depression risk
• • Two preclinical studies show mitragynine reduces opioid self-administration without tolerance, cross-tolerance, or addiction potential
• • 7-hydroxymitragynine (a minor alkaloid and active metabolite) shows 22.5x higher mu-opioid binding than mitragynine and has demonstrated abuse and addiction potential
• • Commercial kratom products vary enormously in alkaloid content (mitragynine: 0.7–38.7%), making dosing unpredictable in real-world use

What they say

Editorial review published in Expert Opinion on Drug Metabolism & Toxicology (2021) by Abhisheak Sharma and Christopher R. McCurdy, University of Florida College of Pharmacy.

Bottom line

Mitragynine's biased opioid agonism makes it a promising OUD treatment candidate, but wide product variability and the abuse potential of its metabolite 7-hydroxymitragynine demand controlled clinical trials and product standardization.