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What Is the Kratom Overdose Risk? A Systematic Literature Review

  • Kratom (o Grundmann and K Smith, Section Editors)
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Abstract

Purpose of Review

The rising public interest in kratom is paralleled by concerns of adverse outcomes, particularly overdose. Such claims span a multitude of reporting modalities, including case reports, analyses of data from poison control and coroners’ reports, and warnings from government agencies. Here we evaluate the literature in efforts to assess kratom’s potential overdose risk. A keyword search of online literature databases identified 12 preclinical studies, 23 case reports, and 15 observational studies/reports meeting our pre-selected criteria.

Recent Findings

Case reports describe outcomes where kratom products are coingested with illicit substances and pharmaceuticals. Opioids are common coingestants, and presentations describe pulmonary edema and findings resembling opioid overdoses. However, seizures and hyperadrenergic features are also common. Where reported, post-mortem mitragynine (MG) concentrations are inconclusive of attributed toxicities. Animal studies found oral LD50s in the range of 200–960 mg/kg for MG, and 200–591 mg/kg for Malaysian total alkaloid extract. Deaths were preceded by restlessness, tremors, and convulsions. Analyses of a variety of reported toxicities yield signs and symptoms that resemble hyperadrenergic components, with autopsies finding coingestants in addition to alkaloids.

Summary

As with any compound ingested in large quantities, it is possible to develop lethal toxicities with kratom in a dose-dependent fashion. Use via the traditional mode of consumption, such as chewing or brewing the leaves as a tea, would require a tremendous amount of kratom to be ingested. The currently available kratom products, and pure alkaloid isolates, greatly increase this risk, in addition to combining kratom with illicit substances, and pharmacokinetic/pharmacodynamic interactions.

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Acknowledgements

The authors would like to acknowledge the contribution made by Karen Goodman, MSLIS, MA, a medical librarian at the Dorothy M. Breene Memorial Library at New Hampshire Hospital, as she assisted with the literature search and procuration of the articles needed for this article.

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Authors and Affiliations

  1. Department of Psychiatry, Dartmouth-Hitchcock Medical Center, Dartmouth’s Geisel School of Medicine, One Medical Center Dr., Lebanon, NH, 03756, USA

    Corneliu N. Stanciu & Gerald L. Rader III

  2. Hope Counseling Services, 14 Leavitt Rd, Pittsfield, NH, 03263, USA

    Samantha A. Gnanasegaram

  3. UF Translational Drug Development Core, Department of Pharmaceutics, University of Florida, Gainesville, FL, USA

    Abhisheak Sharma

  4. UF Translational Drug Development Core, Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA

    Christopher R. McCurdy

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Stanciu, C.N., Gnanasegaram, S.A., Rader, G.L. et al. What Is the Kratom Overdose Risk? A Systematic Literature Review. Curr Addict Rep 10, 9–28 (2023). https://doi.org/10.1007/s40429-022-00464-1

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