Randomized Clinical Trial Finds Kratom Leaf Powder Well-Tolerated With Low Abuse Potential and No Significant Opioid Withdrawal at 15 Days

Why it matters

This is one of the most rigorous controlled human trials of kratom to date. Its findings directly inform FDA's ongoing abuse potential assessment and could influence whether kratom is scheduled as a controlled substance.

The big picture

The FDA uses eight statutory factors under the Controlled Substances Act to assess a substance's abuse potential—including subjective drug effects, withdrawal, and adverse events. Until now, clinical human data on kratom's abuse potential has been limited to surveys and case reports. This industry-funded trial used standardized methodology in kratom-naive healthy adults across multiple dose levels, covering both single-dose and 15-day repeated exposure, providing the clearest controlled picture yet of kratom's pharmacodynamic profile in humans.

Key findings

• 116 kratom-naive healthy adults participated; 49 received active kratom (500–4000 mg leaf powder) and 67 received placebo in a randomized, double-blind design
• No serious adverse events or deaths were reported across all dose levels
• Only the highest dose (4000 mg / 53.2 mg mitragynine) produced statistically significant subjective drug effects compared to placebo in single-dose testing
• No participants met the clinical threshold for opioid withdrawal based on validated COWS or SOWS instruments after 15 days of daily dosing
• Abuse-related adverse events were mild (relaxation, somnolence, hypervigilance) and decreased or plateaued with repeated dosing
• Study was funded by NP Pharma (dba Della Terra Pharmaceuticals); authors from Pinney Associates consult to the kratom industry

What they say

"Oral administration of kratom at tested doses was well tolerated and associated with modest, dose-related subjective effects, minimal withdrawal symptoms, and low abuse-related adverse event rates," the authors concluded. "Findings support further research on kratom's safety and therapeutic potential, while emphasizing the importance of dose control and product standardization."

Bottom line

The first rigorous placebo-controlled trial of standardized kratom leaf in humans found no clinically significant opioid withdrawal and only mild subjective effects—though industry funding and absence of real-world high-dose data are important limitations.