Cornel N. Stanciu, MD, MRO, FASAM, FAPA Assistant Professor Dartmouth’s Geisel School of Medicine Hanover, New Hampshire Director of Addiction Services New Hampshire Hospital Concord, New Hampshire
Bryan G. Hybki, MD PGY-4 Psychiatry Resident Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire
Thomas M. Penders, MS, MD Affiliate Professor East Carolina University Brody School of Medicine Attending Psychiatrist Walter B. Jones Alcohol and Drug Abuse Treatment Center Greenville, North Carolina
Acknowledgment The authors would like to acknowledge the contribution of Karen Goodman, MSLIS, MA, Medical Librarian at the Dorothy M. Breene Memorial Library, New Hampshire Hospital, who assisted with the literature search and procuration of the studies needed for this article.
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Metabolism of mitragynine is predominantly carried out through cytochrome P450 (CYP) 3A4, with minor contributions by 2D6 and 2C9. A total of 13 metabolites are produced, including 7-hydroxymitragynine.14 Kratom’s constituents also interact with the CYP system, inhibiting 2C9, 2D6, and 3A4 isoenzymes, and to some extent, 1A2.
Adverse effects can be fatal
An animal study revealed that when administered intravenously, mitragynine and 7-hydroxymitragynine have a similar toxicity profile to heroin.15 When these alkaloids were administered in ascending doses, increases in blood pressure and elevations in liver function tests and creatinine levels from baseline were observed.
Chronic kratom use can result in weight loss, insomnia, constipation, dehydration, skin hyperpigmentation, and extreme fatigue.16 There have also been reports of seizures, delusions, hallucinations, respiratory depression, hepatotoxicity, coma, and death.17,18 An emerging concern is the potential development of fatty liver infiltrates leading to cholestatic liver damage.19-25 One case report described a young man who developed a serum aspartate aminotransferase level of 1,300 IU/L (reference range: 5 to 45 IU/L) and a serum alanine aminotransaminase level of 3,700 IU/L (reference range: 5 to 60 IU/L) after he ingested a kratom product.26 Histologically, the pattern of liver injury mimics primary biliary cholangitis.27
In recent years, calls to poison control centers in the United States related to kratom exposure have risen. Between 2011 and 2017, the number of calls increased from 1 a month to 2 each day.28 The US National Poison Data System has also noted an increase in the number of calls in reference to kratom. It received 2,312 calls from January 2011 through July 2018, with 18 calls occurring in 2011, and 357 within the first 7 months of 2018.29
As of February 2018, the FDA had received reports of 44 deaths associated with kratom.30 There have been reports of fatal overdoses involving kratom, particularly when kratom is co-ingested or used with adulterated and/or combination agents, including one case that involved quetiapine.31-33 There have been reports of deaths believed to be attributed to the use of kratom alone; in one such case, a 35-year-old man experienced a fatal cardiac arrest due to kratom use with no other coingestants.34 Among the reports of deaths in which kratom was the only substance consumed, the mitragynine blood levels of the deceased individuals were found to be higher than the levels associated with individuals who had consumed traditional kratom teas.29
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