Limitations of the Huestis Kratom Dose Study for Policy Use

What the January 2026 human kratom dose study does—and does not—establish for lawmakers

In January 2026, a study led by Marilyn Huestis et al. was published in Therapeutic Drug Monitoring examining the safety and tolerability of a commercial kratom product administered to healthy adult volunteers. The study has since been cited in policy discussions as evidence that kratom is safe and should not be subject to additional regulation.

A careful review of the paper shows that this interpretation extends well beyond what the study was designed to evaluate.

The sections below summarize key limitations and findings that are important for lawmakers to understand when considering how, or whether, this study should inform public policy.

1. Study population does not reflect real-world use

The study evaluated a narrowly defined population under controlled conditions:

• Healthy adults only
• No chronic kratom users
• No participants with liver disease, psychiatric illness, or substance use disorder
• No concurrent prescription or recreational drug use
• Exclusion of individuals with known CYP450 polymorphisms

This design differs substantially from real-world consumption patterns, where users may take kratom daily, combine it with other substances, or have underlying medical conditions.

A study designed to minimize risk exposure cannot be assumed to reflect population-level safety.

2. Liver enzyme elevations occurred during the study

Despite extensive screening and monitoring, elevations in liver enzymes were observed during repeated dosing.

Findings reported in the study include:

• Participant withdrawals due to rising ALT and AST levels
• Resolution of enzyme elevations after dosing was stopped
• More frequent findings in higher-dose cohorts
• Use of predefined stopping criteria to prevent further injury

The authors recommend liver monitoring in future studies, which signals the need for continued caution rather than confirmation of safety.

3. Clinically significant adverse events were reported

The study documents several adverse events that are relevant to public safety considerations:

• Episodes of syncope, including one described as “seizure-like activity” shortly after dosing
• Severe gastrointestinal illness requiring withdrawal from the study
• Intoxication-like symptoms at higher doses, including dizziness, somnolence, nausea, and vomiting

While these events occurred in a supervised setting, they raise questions about impairment, driving safety, and occupational risk in unsupervised use.

4. Adverse events increased with dose

Among participants receiving the active product:

• More than half reported treatment-emergent adverse events
• The number of events increased with dose level
• The highest-dose cohort experienced a substantial cumulative adverse-event burden
• Multiple participants were withdrawn due to suspected product-related effects

The characterization of the product as “well tolerated” should be read in the context of controlled dosing and early discontinuation when adverse effects emerged.

5. Abuse potential and long-term risk were not assessed

The study concludes that there was no meaningful abuse potential; however, important limitations apply:

• Participants were kratom-naïve or abstinent for at least 12 months
• Dosing was clinic-administered, once daily, and time-limited
• No self-administration or reinforcement models were used
• Abuse-liability testing was deferred to a separate, unpublished manuscript

As a result, the study does not address addiction risk associated with chronic or unsupervised use.

6. Funding and regulatory context

The study was funded by the manufacturer of the product evaluated (NP Pharma), using its proprietary kratom formulation (MitraLeaf). The authors disclose compensation related to study design, analysis, and publication.

In addition, the same product has previously been submitted to the FDA as a new dietary ingredient and did not establish a reasonable expectation of safety for use as a dietary supplement.

While the dietary supplement review process is distinct from clinical research, this regulatory history provides important context when considering how the study’s findings should be applied.

7. Policy implications

The study provides limited information about short-term tolerability in a carefully selected population. It does not establish:

• Safety in chronic or high-frequency use
• Safety of retail kratom products as sold
• Population-level risk
• Absence of liver or neurologic harm
• Low abuse or dependence potential in real-world settings

Accordingly, the study should not be relied upon as a standalone basis for policy decisions regarding deregulation or normalization.

Summary for policymakers

This study does not demonstrate that kratom products are broadly safe for consumer use. Instead, it highlights the need for:

• Further long-term safety evaluation
• Assessment in real-world populations
• Clear regulatory oversight

Policy decisions should reflect the study’s limitations as well as its findings.