Pharmacology • Mechanism
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7-Hydroxymitragynine is the active metabolite driving MOR analgesia
Mitragynine converts to 7-OH, mediating μ-opioid effects—central to benefits and opioid-like risks.
Summary
Bench→in vivo work demonstrates 7-OH formation and MOR-dependent analgesia, explaining respiratory-depression potential at high doses and with sedatives.
Kruegel AC, Gassaway MM, Kapoor A, et al. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Cent Sci. 2019;5(6):992-1001. PubMed • PMC
Overview • Clinical
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Kratom—Pharmacology, clinical implications, and outlook
Clear review of alkaloids, receptor actions, and clinical toxicology—useful primer for counseling.
Eastlack SC, Cornett EM, Kaye AD. Kratom—Pharmacology, Clinical Implications, and Outlook. Pharmacotherapy. 2020;40(11):1103-1115. PMC
Epidemiology • Poison Centers
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NPDS: U.S. poison-center exposures, 2011–2017
Calls rose from 13 to 682; common effects include tachycardia, agitation, drowsiness, seizures; some major outcomes.
Post S, Spiller HA, Chounthirath T, Smith GA. Kratom exposures reported to United States poison control centers: 2011–2017. Clin Toxicol (Phila). 2019;57(10):847-854. PubMed
Epidemiology • Poison Centers
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CDC MMWR: Kratom exposures, 2010–2015
Early CDC note documenting increasing reports and severity; sets baseline trend.
Anwar M, Law R, Schier J. Notes from the Field: Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers — United States, 2010–2015. MMWR. 2016;65(29):748-749. PubMed
Overdose Surveillance • SUDORS
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Kratom detected in overdose deaths (27 states, 2016–2017)
Kratom-positive deaths are uncommon but real; polysubstance involvement frequent.
Olsen EOM, O’Donnell J, Mattson CL, et al. Unintentional Drug Overdose Deaths with Kratom Detected — 27 States, July 2016–December 2017. MMWR. 2019;68(14):326-327. CDC
DDI • Prediction (CYP3A/CYP2D6)
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Mechanistic modeling predicts clinically relevant kratom–drug interactions
Time-dependent CYP3A inhibition suggests ↑ exposure of susceptible substrates; supports caution with polypharmacy.
Summary
In vitro inhibition + IVIVE/PBPK modeling indicate mitragynine can inhibit CYP3A (and possibly CYP2D6), predicting DDIs with certain opioids, benzos, CCBs, and other CYP3A substrates.
Tanna RS, Tian DD, Cech NB, et al. Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations. Drug Metab Dispos. 2021;49(11):949-958. PMC
DDI • Clinical
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First clinical assessment of kratom’s drug–drug interaction potential
Human data show CYP3A inhibition signal; anticipate ↑ exposure of drugs like midazolam analogs.
Summary
Combines clinical study with PBPK; findings align with mechanistic predictions. Practical counseling point for clinicians and pharmacists.
Tanna RS, Tai W, Rettie AE, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther. 2023;113(7):1426-1437. PMC
DDI • Case
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Case report: toxicity from suspected kratom–drug interaction
Real-world vignette consistent with CYP450 inhibition; underscores careful med reconciliation.
Summary
Clinical course and timing suggest a pharmacokinetic interaction. Complements modeling and clinical DDI work; good teaching case.
Brogdon HD, Krepkova LV, Ilyas M, et al. A Case of Potential Pharmacokinetic Kratom-Drug Interaction Resulting in Toxicity via CYP450 Inhibition. J Med Toxicol. 2022;18(3):219-223. PMC
Hepatology • Series
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DILIN experience: kratom-associated liver injury
Cholestatic/mixed patterns predominate; most recover with cessation; emphasizes supplement history taking.
Summary
Multicenter case series with product analysis. Describes presentation, labs, histology, and course; helpful for differentiating from autoimmune cholestasis.
Ahmad J, Odin JA, Hayashi PH, et al. Liver Injury Associated with Kratom, a Popular Opioid-Like Product: The DILIN Experience. Clin Liver Dis (Hoboken). 2020;15(6):241-246. PMC
Hepatology • Case
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Cholestatic hepatitis from prolonged kratom use
Classic hepatology case; beware autoimmune mimicry and ensure targeted supplement history.
Summary
Granular labs and histology; early sentinel case that anchors the hepatotoxicity signal for kratom in the literature.
Dorman C, Wong M, Khan A. Cholestatic hepatitis from prolonged kratom use: a case report. Hepatology. 2015;61(3):1086-1087. PubMed
Neurology • Seizures
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Kratom-induced tonic-clonic seizures (case)
Consider kratom in new-onset seizures, especially with polysubstance use.
Summary
Documented generalized seizures temporally associated with kratom; adds to risk awareness in emergency and neurology settings.
Afzal H, Esang M, Ferguson C, Kahn F. A Case of Kratom-Induced Seizures. Cureus. 2020;12(1):e6641. PMC
Neurology • Seizures
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Breakthrough seizures in epilepsy after kratom
Case series linking kratom use with seizure recurrence—advise caution for seizure-prone patients.
Summary
Three epilepsy patients experienced breakthrough seizures temporally related to kratom; reinforces avoidance counseling.
Burke DJ, Singh N, Cheesman M, Nacca N. Breakthrough Seizure Associated with Kratom Use in Patients with Epilepsy. Cureus. 2021;13(3):e13970. PMC
Cardiology
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Acquired type-1 Brugada pattern linked to chronic kratom use
Reversible Brugada phenotype seen after heavy kratom use — suggests arrhythmic risk and need for ECG awareness.
Summary
ECG changes resolved after cessation; adds to case reports of QT and Brugada-pattern toxicity from kratom use.
Holton K, Yan J, Walter G, et al. Acquired Type 1 Brugada Syndrome Induced by Chronic High-Dose Kratom Use. Cureus. 2024;16(4):e58175. PMC
Perinatal • NAS
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Neonatal abstinence syndrome after maternal kratom use
Infants can develop withdrawal requiring pharmacologic treatment; routine toxicology may miss mitragynine.
Summary
First Pediatrics case describing kratom-related NAS; critical for OB and NICU screening protocols.
Eldridge WB, Foster C, Wyble L, Thomas J. Neonatal Abstinence Syndrome Due to Maternal Kratom Use. Pediatrics. 2018;142(6):e20181839. PubMed
Perinatal • NAS (case)
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Neonatal withdrawal following in-utero exposure to kratom
Reinforces NAS risk and importance of asking about herbal products during pregnancy intake.
Summary
BMJ Case Report confirming kratom withdrawal presentation in a newborn; adds international confirmation of risk profile.
Davidson L, Abassi H. Neonatal abstinence syndrome secondary to “kratom”. BMJ Case Rep. 2019;12:e230061. PMC
Informational only — not medical advice. Outcomes vary with testing and co-exposures. Encourage patients to disclose all “herbal” products.