Comment on HHS-OASH-2026-0232, HHS-OASH-2026-0232-0001, 2026-13608

I write to oppose the proposed 0.05 % threshold for 7-hydroxymitragynine (7-OH). Human clinical data, missing from the Pinney Associates Eight-Factor Analysis, show that even trace 7-OH (<0.01 %) in kratom leaf produces measurable opioid exposure and adverse effects. Setting any non-zero limit will leave consumers unprotected. 1 Trace 7-OH already yields systemic opioid exposure In a 2026 FDA-funded trial (Huestis et al.), capsules containing <0.01 % 7-OH delivered dose-dependent plasma 7-OH up to ~22 ng/mL. Twenty-to-thirty percent of absorbed mitragynine was converted to 7-OH, proving that metabolism alone creates a substantial opioid burden; adding exogenous 7-OH only amplifies it. 2 Clinically significant harms at <0.01 % 7-OH * Dose-related nausea, dizziness, headache, somnolence. * Two participants withdrawn for ALT/AST elevations (>5&times; ULN) at the highest dose. * One mid-dose participant experienced vasovagal syncope with seizure-like activity. These findings emerged with a starting 7-OH concentration four times lower than the proposed limit. 3 Controlled PD study disproves “safe” trace levels A separate 2026 placebo-controlled dose-finding study (Reissig et al.) used kratom containing ~0.012 % 7-OH—still below 0.05 %. It showed classic &mu;-opioid effects (pupillary constriction), statistically significant “drug-liking” and “high,” plus nausea and vomiting from 8 g upward. The dose–effect curve was linear, not threshold-based. 4 The “natural vs. synthetic” distinction is meaningless 7-OH produced by metabolism is chemically identical to any added 7-OH; receptors do not differentiate. Allowing 0.05 % external 7-OH merely stacks potent opioid on top of the body’s own conversion of mitragynine. 5 Surveillance already shows an emerging problem Poison-center data logged 186 exposures to 7-OH in 2025–26, most classified as abuse or intentional misuse—months before a product code even existed. Recommendation Because measurable harms appear below 0.01 % and metabolism guarantees additional 7-OH even when none is added, the only scientifically defensible standard is “not detected” at the analytical limit of quantitation (effectively 0.000 %). The proposed 0.05 % threshold would legitimize products that deliver pharmacologically active opioid doses and invite further public-health harm.