Beyond kratom: Concentrated 7-hydroxymitragynine and mitragynine pseudoindoxyl products, an MME potency assessment Highlights ••
Morphine milligram equivalent (MME) estimates were derived for the three primary opioid-active kratom alkaloids: mitragynine, 7-hydroxymitragynine (7-OH), and mitragynine pseudoindoxyl.
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Relative to morphine, μ-opioid receptor (MOR)-referenced potency was lower for mitragynine (geomean MME 0.13) and higher for 7-OH and mitragynine pseudoindoxyl (geomean MME 4.3 and 4.8, respectively).
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Estimated mean per-serving MME across 90 marketed products ranged from 2.7 (powders) to 31 (tablets), with 7-OH and mitragynine pseudoindoxyl driving the highest values.
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High per-serving mitragynine mass alone produced elevated MME in some product types (e.g., gummies, soft gels) despite minimal 7-OH or mitragynine pseudoindoxyl content.
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FDA pharmacovigilance screening identified frequent reports of dependence, withdrawal, and psychiatric symptoms among users of 7-OH and mitragynine pseudoindoxyl, though polypharmacy effects could not be ruled out. Abstract Traditional kratom (Mitragyna speciosa) products consist of botanical leaf derivatives dominated by mitragynine, with minimal 7-hydroxymitragynine (7-OH) or mitragynine pseudoindoxyl content. Kratom-branded products containing concentrated 7-OH and mitragynine pseudoindoxyl have proliferated since 2024 and are pharmacologically distinct from and more potent than mitragynine at the μ-opioid receptor (MOR). Morphine milligram equivalent (MME) values for mitragynine, 7-OH, and mitragynine pseudoindoxyl were estimated. Functional in vitro and in vivo data from 13 studies informed alkaloid-specific MME estimates, which were applied to alkaloid concentrations in commercial products to derive per-serving and per-day MME totals. Relative to morphine, MOR-referenced potency was lower for mitragynine (geomean MME 0.13) and higher for 7-OH and mitragynine pseudoindoxyl (geomean MME 4.3 and 4.8, respectively). Mean per-serving MME ranged from 2.7 (powders) to 31 (tablets) across product types. Screening of U.S. Food and Drug Administration pharmacovigilance data identified frequent reports of dependence, withdrawal, and psychiatric symptoms among users of 7-OH and mitragynine pseudoindoxyl, but polypharmacy effects could not be ruled out. These findings support pharmacological differentiation between traditional, mitragynine-dominant kratom preparations and concentrated 7-OH/mitragynine pseudoindoxyl products, consistent with the U.S. Drug Enforcement Administration's July 2026 notice of scheduling intent, while traditional preparations retain non-negligible, mitragynine-ceiling-limited opioid activity. sciencedirect.com/science/ar… Date: January 2027 Article: 106272 Volume: Volume 173