Kratom is an herbal made from leaves of a tropical evergreen tree (Mitragyna speciosa) that is native to Southeast Asia. Extracts from the leaves of the kratom tree have psychotropic and opioid-like activity, which has led to their use as a recreational drug. Kratom has been linked to rare instances of clinically apparent acute liver injury.
Kratom is a botanical extract derived from the leaves of a tropical evergreen tree (Mitragyna speciosa), which belongs to the coffee family and is indigenous to Thailand, Myanmar and Malaysia. In Southeast Asia, kratom has been used for decades as an herbal medication to treat chronic pain, increase energy and stamina, treat chronic pain and diarrhea, and as a substitute for opium or for opium withdrawal. The leaves have multiple components, including psychoactive alkaloids that have opioid-like activity. In many Southeast Asian countries, chewing Mitragyna speciosa leaves is a not uncommon practice and not considered addictive. The effects of chewing kratom leaves include enhanced alertness, talkativeness and sociability. Extracts of kratom have been used to treat chronic pain, diarrhea and cough. The psychoactive effects of kratom have led to its use recreationally as a cannabis-like drug. Higher doses can cause agitation, hypertension, dyspnea and confusion. Overdoses of kratom can cause seizures, coma and death. Kratom has become a substance of abuse and it has not been shown to have any beneficial medical uses. In 2014, the US FDA banned the inclusion of kratom in dietary supplements because of safety concerns, with potential adverse effects including respiratory depression, aggression, hallucinations, delusions, insomnia, vomiting and severe withdrawal.
Chronic use of kratom recreationally has been associated with rare instances of acute liver injury. The onset of injury is usually within 2 to 8 weeks of starting regular use of kratom powder or tablets, with symptoms of fatigue, nausea, pruritus and dark urine followed by jaundice. The pattern of liver injury is typically cholestatic or mixed, and it can be severe with serum bilirubin levels rising above 20 mg/dL. The severe cholestasis can be accompanied by acute renal failure and bone marrow toxicity. Fever is common, but not rash or eosinophilia and autoantibodies are usually absent. The cholestasis can be prolonged, but usually resolves spontaneously. Corticosteroids have been used in cases of suspected kratom hepatotoxicity, but their efficacy is unproven. Kratom is a banned substance and considered an agent of abuse, for which reason it is usually not listed or discussed in review articles on HDS related liver injury.
Likelihood Score: C (probable cause of clinically apparent liver injury).
Mechanism of Injury
The cause of liver injury due to kratom is unknown. It is often used with other agents, including drugs of abuse, and its causative relationship to liver injury in published cases is not always clear.
Outcome and Management
Patients who present with acute liver injury due to kratom usually recover rapidly once it is discontinued. There is no evidence that corticosteroids shorten the course of illness or improve outcomes. Patients should be warned against further use of kratom and multiingredient nutrition supplements that might contain it.
Clinical cases of drug-induced liver injury that have been submitted to LiverTox ("Submit a Case Report") are available for review. Most of these reference cases are from the Drug-Induced Liver Injury Network, but others are from users of LiverTox who have submitted data from an actual clinical case. All cases have been reviewed and cleared of personal identifiers and a brief comment added by the LiverTox editors. Click on the following link to view the submitted case reports that have been made publically available.
Submitted Cases on Kratom
REPRESENTATIVE TRADE NAMES
Kratom – Generic
Herbal and Dietary Supplements
||CAS REGISTRY NO.
|| Herbal mixture
References updated: 10 April 2018
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Neerman MF, Frost RE, Deking J. A drug fatality involving Kratom. J Forensic Sci 2013; 58 Suppl 1: S278-9. PubMed Citation (17 year old man was found dead with empty bottles and boxes of kratom, autopsy showing bilateral pulmonary edema and high mitragynine blood levels).
Ulbricht C, Costa D, Dao J, Isaac R, LeBlanc YC, Rhoades J, Windsor RC. An evidence-based systematic review of kratom (Mitragyna speciosa) by the Natural Standard Research Collaboration. J Diet Suppl 2013; 10:152-70. PubMed Citation (Systematic review of safety and efficacy of kratom [Mitragyna speciosa] concludes that there is a lack of evidence in support of kratom having any clinical indication, its historic uses being as an analgesic, antitussive, anxiolytic, and treatment for opiate withdrawal).
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2018; 11: 79-82. PubMed Citation (38 year old man developed fever followed by dark urine and jaundice while taking kratom [bilirubin 5.1 mg/dL, ALT 389 U/L, Alk P 304 U/L]; a liver biopsy showed acute cholestatic hepatitis, and he improved rapidly upon stopping).
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