Kratom toxicity

Background

Kratom flowers and foliage.
Typical powdered Kratom for commercial use.
  • Derived from Mitragyna speciosa, a tropical evergreen tree in the coffee family native to Southeast Asia
  • Leaves contain over 40 alkaloids; the two most clinically relevant are:
    • Mitragynine (most abundant, up to 66% of total alkaloid content) — partial mu-opioid receptor agonist[1]
    • 7-Hydroxymitragynine (7-OH) (minor constituent, <2% of alkaloid content) — approximately 5-fold greater mu-opioid affinity than mitragynine[1]
  • Both alkaloids exhibit G-protein biased agonism at mu-opioid receptors with limited beta-arrestin recruitment (theoretically less respiratory depression than classical opioids, though still reported)[1]
  • Additional receptor activity at alpha-1A, alpha-2A, 5-HT1A, 5-HT2A, D1, and D2 receptors contributes to mixed stimulant-opioid clinical picture[2]
  • Mitragynine is metabolized by CYP3A4 to 7-hydroxymitragynine (a more potent metabolite) and inhibits CYP2D6 and CYP3A4, creating significant potential for drug-drug interactions[3]
  • Available in the US as powder, capsules, tablets, extracts, and liquid "shots" sold at gas stations, smoke shops, and online
    • Products are unregulated, with highly variable alkaloid content and potential for contamination (Salmonella, heavy metals including lead)[4]
  • Estimated 1.7 million Americans aged ≥12 used kratom in 2021[4]
  • Not FDA-approved for any indication; not a legal dietary supplement or food additive[4]
  • Federally unscheduled but banned in several states (Alabama, Arkansas, Indiana, Vermont, Wisconsin, Louisiana); regulated in many others[5]
  • Patients commonly use for self-treatment of chronic pain, opioid withdrawal, depression, and anxiety
    • Approximately one-third of users co-ingest with other substances[6]

Clinical Features

  • Effects are dose-dependent and may mimic both opioid and stimulant toxicity
  • Onset of effects typically within 10-20 minutes of ingestion; duration 2-5 hours

Low-Dose Effects (<5 g)

  • Stimulant effects predominate
  • Increased alertness and energy
  • Tachycardia, hypertension
  • Agitation, jitteriness
  • Decreased appetite

High-Dose Effects (>5 g)

Severe/Complicated Presentations

Kratom Withdrawal

  • Occurs with chronic use; onset typically within 12-24 hours of last dose[8]
  • Resembles mild-moderate opioid withdrawal: myalgias, rhinorrhea, diaphoresis, insomnia, irritability, nausea, diarrhea
  • Generally less severe than traditional opioid withdrawal
  • Can be scored using the Clinical Opiate Withdrawal Scale (COWS)

Differential Diagnosis

Drugs of abuse

Evaluation

  • Primarily a clinical diagnosis — ask specifically about kratom, herbal supplements, and "gas station" products
  • Kratom does NOT appear on standard urine drug screens[7]
    • May cause false-negative opioid screen despite opioid-like presentation
    • Specialized testing for mitragynine exists but is not widely available and generally not clinically useful in the acute setting
  • Consider early consultation with Poison control (1-800-222-1222)

Labs

ECG

Management

  • Focus on ABCs and symptom-directed treatment
  • Consider early Poison control consultation (1-800-222-1222)

Respiratory Depression

  • Supplemental oxygen, BVM ventilation as needed
  • Naloxone — effective for kratom-induced respiratory depression due to mu-opioid agonism[11]
    • Standard dosing as per opioid toxicity protocols
    • Be aware of potential for rebound respiratory depression within 24 hours per poison control center reports[11]

Agitation / Sympathomimetic Features

Seizures

Kratom Withdrawal

  • Symptom-directed treatment similar to opioid withdrawal:
  • Medication-assisted treatment for opioid use disorder:
    • Buprenorphine — most commonly reported for kratom withdrawal/dependence; can be initiated in the ED per standard protocols[6]
    • Methadone — alternative for patients not candidates for buprenorphine

Hepatotoxicity

  • Discontinue kratom
  • Supportive care; most cases resolve spontaneously[9]
  • GI consultation for severe hepatic injury (bilirubin >20 mg/dL, coagulopathy, or signs of acute liver failure)
  • Corticosteroids and NAC have been used in case reports but efficacy is unproven[9]

Drug Interactions

  • Be aware that mitragynine inhibits CYP3A4 and CYP2D6[3]
  • Potential to increase levels of co-ingested medications metabolized by these pathways (e.g., benzodiazepines, methadone, certain antipsychotics, SSRIs)
  • Polydrug exposure is common and may significantly increase morbidity and mortality

Disposition

  • Discharge if:
    • Mild symptoms (nausea, mild stimulant effects) that resolve with observation and supportive care
    • Normal vital signs and mental status at time of disposition
    • Able to tolerate PO
  • Observation / Admission if:
  • ICU admission for:
  • For all patients: provide counseling on risks of kratom, advise cessation, and consider referral to addiction medicine if regular use or dependence is identified
  • Provide naloxone prescription at discharge if ongoing use is anticipated

See Also

External Links

References

  1. ↑ 1.0 1.1 1.2 Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. 2018;134(Pt A):108-120.
  2. ↑ Yusof SR, Zakaria Z, Amir Rawa MS, et al. Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers. Front Pharmacol. 2021;12:751656.
  3. ↑ 3.0 3.1 Tanna RS, Tian DD, Cech NB, et al. Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations. J Pharmacol Exp Ther. 2021;376(1):64-73.
  4. ↑ 4.0 4.1 4.2 U.S. Food and Drug Administration. FDA and Kratom. Updated February 2024. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom
  5. ↑ Congressional Research Service. Kratom Regulation: Federal Status and State Approaches. LSB11082. 2024.
  6. ↑ 6.0 6.1 Washington Poison Center. Kratom and 7-hydroxymitragynine poisoning. 2025. https://www.wapc.org/data/data-blogs/kratom-and-7-hydroxymitragynine-poisoning/
  7. ↑ 7.0 7.1 Eastlack SC, Cornett EM, Kaye AD. Kratom—Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review. Pain Ther. 2020;9(1):55-69.
  8. ↑ 8.0 8.1 Narrative Review of Kratom in the Emergency Department. Auctores. 2025.
  9. ↑ 9.0 9.1 9.2 LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Kratom. National Institute of Diabetes and Digestive and Kidney Diseases; 2020.
  10. ↑ Poison Control. What is kratom? https://www.poison.org/articles/kratom
  11. ↑ 11.0 11.1 11.2 Mikkelsen A, Van Roekel C, Grande EJ, et al. The Great Imitator: A Case of Accidental Kratom Overdose. Cureus. 2023;15(7):e42497.
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