Kratom: An Emerging Toxicologic Concern in the ED

Source: https://www.poison.org/articles/kratom

Kratom

  • Herbal product

  • Derived from Mitragyna speciosa tree of Southeast Asia

  • Contains 40 bioactive alkaloids

  • Growing use in the United States with increasing presentations to emergency departments (ED) for toxicity and withdrawal.

Source: https://www.vcuhealth.org/news/is-kratom-safe-rising-health-concerns-explained/

History and Epidemiology

  • Used in SE Asia for over a century (2)

    • Leaves were chewed or brewed into tea

  • Therapeutic uses

    • Analgesic

    • Antidiarrheal

    • Antispasmodic

    • Antipyretic

  • Functional uses

    • Stimulant to increase endurance and productivity among manual laborers

  • Popularity in US has increased

  • Legal at Federal level; regulated in 24 states and DC

    • Variability in potency, preparation and alkaloid content (3)

  • Marketed online and in gas stations and head shops

  • “natural remedy” for pain, anxiety, fatigue and opioid withdrawal

    • Appeal is particularly strong among patients with opioid use disorder who seek alternatives to methadone or buprenorphine (1)

  • Historical accounts describe its use for withdrawal management in Thailand and Malaysia dating back to the 1800s (2)


Ohio-Specific Laws & Regulations

  • Currently legal in Ohio but can only be sold in natural, dried leaf or powdered form

    • August 2025, Governor DeWine called to classify all forms as scheduled I controlled substances

    • Proposed bans/regulation are introduced in the House and Senate

    • FDA is recommending 7-hydroxymitragynine (7-OH) as Schedule I

  • Regulation vs legalization

    • Risks and benefits to both


Pharmacology & Mechanism of Action

  • 40 Bioactive alkaloids - 4 primary agents identified (5)

  • Mitragynine

    • Most abundant

    • Active at mu, delta and kappa opioid receptors

    • Interacts with adrenergic and serotonergic systems

  • 7-hydroxymitragynine

    • Metabolite of mitragynine (hepatic)

    • Significantly more potent

    • 13x higher affinity for opioid receptors compared to morphine (7)

    • 46x more potent than mitragynine (7)

  • Dual actions à dual effects

    • CNS stimulant effects at low doses & opioid-like sedative effects at higher doses


Clinical Presentations in the ED

  • Acute toxicity

    • Common effects

      • Agitation, tachycardia, drowsiness, vomiting, confusion

    • Severe effects

      • Seizures, hallucinations, respiratory depression, coma, cardiac and respiratory arrest

  • Withdrawal

    • Similar to opioid withdrawal and is treated the same;

    • Symptoms

      • Piloerection, rhinorrhea, abdominal cramping, diarrhea, lacrimation, mydriasis, insomnia, irritability (1)

    • Onset

      • 12-24 hours after last use (2)

    • Duration

      • 3-7 days, severity correlating to chronicity and dose (2)


Management in the ED

  • Acute toxicity

    • ABCs remain the cornerstone

    • Naloxone (3,4)

  • Withdrawal

    • Buprenorphine and methadone

    • Dosing the same as with OUD

  • Symptomatic therapy

    • Clonidine for autonomic hyperactivity

    • Dicyclomine for abdominal pain

    • Ondansetron for nausea and vomiting


Take Home Points

  • Kratom is an unregulated herbal product increasingly seen in US emergency departments

  • Contains multiple alkaloids with mixed opioid, adrenergic and serotonergic activity

  • Clinical effects are dose-dependent

  • Stimulant at lower doses and opioid-like sedation

  • Presentations include nausea, tachycardia and agitation but severe toxicity is possible

  • Naloxone may be effective in reversing kratom-induced respiratory depression

  • Withdrawal resembles opioid withdrawal and should be managed in similar fashion

TOX Blog Main Page

AUTHORED BY: ABBY WISSMAN, DO, PGY3

FACULTY EDITING BY: LAUREN PORTER, DO

References

  1. Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. Kratom use and toxicities in the United States. Pharmacotherapy. 39.7 (2019): 775-777.

  2. Kerrigan, Sarah, and Stephanie Basiliere. "Kratom: A systematic review of toxicological issues." Wiley Interdisciplinary Reviews: Forensic Science 4.1 (2022): e1420.

  3. Overbeek DL, Abraham J, Munzer BW. Kratom (Mitragynine) Ingestion Requiring Naloxone Reversal. Clin Pract Cases Emerg Med. 2019 Jan 4;3(1):24-26.

  4. Ahmed S, Tran QV, McLean M. The Great Imitator: A Case of Accidental Kratom Overdose. Cureus. 2023 Aug 8;15(8):e43144.

  5. Henningfield JE, Chawarski MC, Garcia-Romeu A, Grundmann O, et al. Kratom withdrawal: Discussions and conclusions of a scientific expert forum. Drug Alcohol Depend Rep. 2023 Mar 15;7:100142.

  6. Arhin M, Mobley J, Hamad H, Remick P. Successful Management of Kratom Use Disorder With Buprenorphine and Naloxone. Cureus. 2023 Jun 29;15(6):e41146.

  7. Sokup B, Pippin MM. Kratom. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK585120/

  8. https://www.poison.org/articles/kratom

  9. https://www.vcuhealth.org/news/is-kratom-safe-rising-health-concerns-explained/

ToxLauren McCaffertytox, toxicity, kratom