ANTI-KRATOM ASSOCIATION

Six Exhibits. Six Very Different Problems.

The six documents do not form a coherent body of evidence establishing that retail kratom is safe, nonaddictive, or medically beneficial. In several places, the documents themselves undermine the claims being made from them.

1. Yue et al. — "Abuse Liability of Mitragynine Assessed With a Self-Administration Procedure in Rats"

What it is being used to say:

That is considerably broader than what the experiment tested.

This was a study of six male rats, trained to intravenously self-administer methamphetamine. Researchers then substituted intravenous doses of isolated mitragynine. The rats did not self-administer mitragynine above saline levels, and the authors concluded that their particular self-administration experiment suggested limited abuse liability.

That's the evidence.

• Not humans.
• Not oral kratom.
• Not chronic use.
• Not withdrawal after months or years.
• Not commercial leaf products.
• Not extracts.
• Not the dozens of other kratom alkaloids.

And the paper itself practically puts a warning label on attempts to generalize it. The authors wrote that there were "several reasons to exercise caution" in generalizing from the failure of mitragynine self-administration. They acknowledged that drug self-administration can depend on experimental conditions and specifically conceded that circumstances might yet be found under which mitragynine is reliably self-administered.

Even more awkwardly, the paper discusses prior studies in which mitragynine did produce conditioned place preference, an established measure of drug reward, and notes that the effect was blocked by naloxone—implicating opioid receptors.

And 7-hydroxymitragynine? The same paper summarizes evidence that 7-OH was self-administered by rats, unlike mitragynine.

2. Grundmann et al. — "Prevalence and Use Patterns of Kratom in a US Nationally Representative Sample"

What it is being used to say:

This one deserves especially close scrutiny because the giant national number comes from 9.1% prevalence.

The study explicitly describes its methodology as "non-probabilistic" sampling. Participants came from a commercial research company's opt-in marketing panels.

That's not a minor footnote.

The paper says 66,121 panelists were invited. Only 11,545 started the survey, and the final kratom sample consisted of 1,049 respondents. Non-kratom users were screened out of the full survey, while only about 1,000 nonusers had demographic information retained.

Then those 1,049 kratom users became:

And from there, approximately:

There is a rather substantial elephant sitting beside that estimate: the same paper acknowledges dramatically lower national estimates. It cites NSDUH past-year prevalence of 0.7% and another survey's lifetime prevalence of 6.1%.

A later FDA clinical paper in your packet states that NSDUH estimated approximately 1.7 million Americans aged 12+ used kratom in 2021.

There is another detail lawmakers deserve to know: the authors thank the Global Kratom Coalition for providing the survey data. Yet the publication reports no funding and no potential conflicts.

The proper description isn't:

It's:

Not quite as good on a lobbying slide.

Far more accurate.

3. Garcia-Romeu, Cox, Smith et al. — "Kratom: User Demographics, Use Patterns, and Implications for the Opioid Epidemic"

What it is being used to say:

Now look at who was asked.

Participants were recruited through websites "of interest to kratom users," including the American Kratom Association, Erowid and Reddit.

And this isn't some tiny portion of recruitment.

Then this self-selected online population of kratom users was asked how well kratom worked.

Unsurprisingly, they liked it.

The study reported extremely high self-rated effectiveness for pain, anxiety and depression, and 59.1% were daily users.

Among people who said they used kratom to reduce opioids, 87.3% said it treated opioid withdrawal, while 99.2% said they would recommend kratom for withdrawal.

Well.

If you recruit half your sample through the American Kratom Association and much of the remainder from social-media communities populated by kratom users, you have not created a randomized clinical trial of opioid-use-disorder treatment.

You have surveyed kratom users about kratom.

But here is the extraordinary part:

They acknowledge that their convenience sample likely selected people who were more positively inclined toward kratom, may have missed former users who quit because of adverse effects, and therefore could underestimate adverse effects and overestimate benefits.

4. Aly & Grundmann — "A Review of Kratom Product Evolution and Its Associated Health Outcomes"

What it is being used to say:

Read beyond the abstract.

Yes, Aly and Grundmann distinguish traditional leaf from concentrated products and argue that concentrates likely carry greater risk.

But their own review also says:

• Mitragynine is metabolized to 7-hydroxymitragynine in the human liver.

Even more strikingly, they cite human data in which 7-OH was absent from the administered product but appeared through metabolism and state that approximately one-third of absorbed mitragynine may be metabolized to 7-OH.

The paper also says whole-leaf kratom may produce physical dependence, tolerance and withdrawal, with higher frequency associated with greater dependence signals.

It discusses opioid-like deaths without clear alternative causes, naloxone reversal of kratom intoxication, and concludes that high doses can produce toxicity mediated at least partly through opioid pathways.

It describes hepatotoxicity and potential cardiac toxicity, including hERG inhibition and the theoretical potential for QT prolongation, torsades and sudden death.

And on regulation?

The authors state there is no legally available prescription or OTC drug containing kratom, FDA has not approved it as a dietary supplement, submitted NDIs have not been approved, and more research is needed into efficacy, long-term safety, dependence and drug interactions.

This review is considerably more useful as evidence that we don't yet know enough than as evidence that convenience-store kratom has somehow cleared a safety standard.

5. Reissig et al./FDA — "A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom"

What it is being used to say:

This might be the most devastating document in the packet against that proposition.

This was a small pilot involving 40 recreational polydrug users, with only six active subjects at each kratom dose. It was designed in part to inform a future human abuse-potential study.

What happened?

At 12 grams, kratom increased drug liking, good drug effects and feeling high. The authors explicitly describe those as effects associated with drugs of abuse.

The paper also describes mitragynine's affinity for μ-opioid receptors and notes that conditioned-place-preference experiments have demonstrated rewarding properties. It specifically states that 7-OH is self-administered in preclinical models, demonstrating reinforcing effects and abuse potential.

And the human pharmacokinetics are particularly inconvenient for any attempt to pretend 7-OH is solely an adulterant added by manufacturers.

Meanwhile, adverse events included vomiting, nausea, dizziness, presyncope, somnolence, anxiety and euphoric mood.

The investigators plainly warn that their tiny sample was insufficient to thoroughly characterize safety and was not powered to detect rare adverse events.

And right up front, the paper reproduces FDA's position that kratom lacks adequate information to provide reasonable assurance of safety as a new dietary ingredient, is not lawfully marketed as a dietary supplement, and cannot lawfully be added to conventional foods.

6. American Kratom Association — "The Case for the Kratom Consumer Protection Act"

What it is being used to say:

This isn't an independent scientific review.

It is an American Kratom Association advocacy presentation arguing for the American Kratom Association's preferred legislation. The title page says exactly what it is: The Case for the Kratom Consumer Protection Act.

And once you recognize that, the presentation becomes a fascinating lesson in selective framing.

Take addiction.

Its slide asks "Is Kratom Dangerously Addictive?" and features the Yue rat self-administration paper to emphasize limited abuse liability.

What isn't on the slide?

• The Yue paper's warning against overgeneralizing those results.
• The conditioned-place-preference evidence.
• The fact that 7-OH was self-administered.
• And, obviously, none of the FDA human data published years later showing measurable drug liking, feeling high and circulating 7-OH after botanical kratom.

Then consider mortality.

The packet emphasizes adulterated Krypton deaths and polysubstance exposure. Yet even the NIDA material reproduced on the next page acknowledges two deaths following kratom exposure alone with no other reported substances.

Then comes the proposed "solution": allow kratom products if, among other requirements, their 7-OH content does not exceed 2% of the alkaloid fraction.

The presentation therefore performs a remarkably convenient maneuver:

• Highlight research favorable to kratom.
• Frame deaths around adulteration and polysubstance exposure.
• Use small animal studies to reassure legislators about addiction.
• Then conclude that the appropriate policy solution happens to be the American Kratom Association's own model legislation.

The problem isn't that these six documents are all worthless

That would actually be too simple.

Some contain useful science.

The problem is what happens to that science when it enters the evidence packet.

• A six-rat IV study becomes "kratom isn't addictive."
• A non-probability marketing survey becomes "24 million Americans."
• A survey recruited heavily through the American Kratom Association becomes evidence that users love kratom and rarely have problems—while the authors' own selection-bias warning disappears.
• A review documenting dependence, withdrawal, opioid pharmacology, human conversion to 7-OH, deaths and major unanswered safety questions gets repackaged as "natural leaf good, 7-OH bad."
• A controlled FDA study finding drug liking, feeling high, opioid effects and circulating 7-OH gets reduced to reassurance because nobody died in a tiny pilot.
• And then the American Kratom Association stacks selected pieces together and calls the result "The Case for the KCPA."

The garbage isn't necessarily in every study.

It's what happens when narrow studies, biased samples, preliminary findings and inconvenient limitations are fed through an advocacy machine and come out the other side as certainty.