Why the “Huestis Kratom Study” Should NOT Be Used to Justify Policy

A critical review of the January 2026 human kratom tolerability trial

In January 2026, a study led by Marilyn Huestis et al. was published in Therapeutic Drug Monitoring claiming that a commercial kratom product was “safe and well tolerated” in healthy volunteers. This paper is now being cited by kratom advocates and industry groups to argue against regulation, scheduling, or enforcement.

That use is deeply misleading.

When examined carefully, the study raises significant safety concerns, demonstrates dose-related toxicity signals, and contains material conflicts of interest that demand caution—not policy reliance.

Below is what legislators need to understand.

1. This was NOT a real-world safety study

The study population was highly artificial:

• Healthy adults only
• No chronic users
• No people with liver disease, psychiatric illness, substance use disorder, or common comorbidities
• No concurrent medications
• Exclusion of participants with known CYP450 polymorphisms

This bears no resemblance to real-world consumers, who frequently:

• Use daily or multiple times per day
• Combine with alcohol, antidepressants, benzodiazepines, stimulants, or opioids
• Have underlying liver, mental health, or substance use conditions

A study that excludes risk does not prove safety.

2. The study repeatedly triggered liver enzyme elevations

Despite aggressive screening and monitoring, liver toxicity emerged anyway.

Key findings reported in the paper:

• Multiple participants were withdrawn due to rising ALT and AST
• Enzymes rose during repeated dosing and resolved after stopping
• Events occurred most clearly in higher-dose cohorts
• The protocol required stopping dosing before injury could worsen

The study acknowledges increased ALT/AST incidence at higher doses and recommends liver monitoring in future studies. That is not reassurance—it is a warning.

3. Serious and alarming adverse events occurred

The paper downplays events that would be unacceptable in most consumer products:

• Vasovagal syncope with “seizure-like activity” less than one hour after dosing
• No EEG was performed
• Event timing strongly suggests drug involvement
• The absence of confirmation is missing data, not proof of safety
• Severe gastroenteritis requiring withdrawal
• Intoxication-like symptom clusters at higher doses: “feeling drunk,” dizziness, vomiting, somnolence, cognitive and physical impairment

These effects matter for driving, working, supervising children, and public safety.

4. “Well tolerated” masks a high adverse-event burden

Among participants receiving active product:

• Over half reported treatment-emergent adverse events
• TEAEs increased with dose
• The highest-dose cohort experienced hundreds of adverse events
• Six participants were withdrawn early due to suspected product-related harm

Calling this “well tolerated” depends entirely on redefining tolerance to mean “participants were stopped before worse injury occurred.”

5. The abuse-potential conclusion is unsupported

The paper claims “no meaningful abuse potential,” yet:

• Participants were naïve or abstinent for ≥12 months
• Dosing was once daily, clinic-controlled, and time-limited
• No self-administration, craving, reinforcement, or escalation paradigms were used
• Cognitive and abuse-liability testing was deferred to a separate, unpublished manuscript

This study cannot answer real-world addiction risk, yet its conclusions are being cited as if it does.

6. Conflicts of interest are not incidental — they are central

This study was:

• Funded by the manufacturer (NP Pharma)
• Conducted using the sponsor’s proprietary product (MitraLeaf)
• Written by authors who received compensation for study design, analysis, and publication

Disclosed conflicts still matter when:

• Results are framed in the most favorable language possible
• Adverse events are minimized rhetorically
• Conclusions extend beyond what the data can support

Industry-funded safety studies should never be treated as regulatory evidence.

7. What legislators are being told vs. what the data actually show

What advocates say

“A large human study proves kratom is safe.”

What the study actually shows

• Short-term exposure in carefully selected healthy adults caused liver enzyme elevations
• Syncope and seizure-like activity occurred soon after dosing
• Severe GI illness required withdrawal
• Intoxication-like effects increased with dose
• Toxicity increased with higher dosing
• “Safety” depended on early termination rules
• Long-term risks were not assessed
• Real-world use was not studied

Bottom line for policymakers

This paper does not justify legalization, deregulation, or normalization.

Instead, it supports the opposite conclusions:

• Dose-dependent toxicity signals are present
• Liver injury risk is real and reproducible
• Acute neurologic and GI events occur even in healthy users
• Long-term and real-world safety remain unknown
• Industry influence shapes the narrative

Using this study to argue against regulation is scientifically irresponsible and politically dangerous.

Why this study quietly confirms the pharmaceutical reality

If this were a credible candidate for mainstream medicine, you would see a normal pharmaceutical pathway: standardized formulation, reproducible dosing, long-term safety programs, drug–drug interaction studies, abuse-liability testing, and controlled clinical trials under FDA oversight.

That is not what is happening.

Instead, we are watching an industry insist a product is “safe” while:

• needing early stopping rules to prevent liver injury,
• producing intoxication-like impairment,
• triggering serious acute events in healthy volunteers, and
• avoiding the very FDA pathway that would force real safety proof.

No serious pharmaceutical manufacturer would try to bring a product to the FDA on this evidence and call it “well tolerated.”
If the best-case scenario still requires medical-style monitoring to prevent harm, it does not belong in convenience stores.