Is kratom (<i>Mitragyna speciosa</i> Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls

Abdullah, Mohd Faizal; Tan, Kian Lam; Narayanan, Suresh; Yuvashnee, Novline; Chear, Nelson Jeng Yeou; Singh, Darshan; Grundmann, Oliver; Henningfield, Jack E.

doi:10.1080/15563650.2020.1812627

Cited by 23 publications

(32 citation statements)

References 37 publications

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“…Similarly, kratom users were also found to be more likely to experience borderline QTc intervals compared to the control group; however kratom users’ odds of prolonged QTc intervals did not increase versus the control group. Therefore, this study concluded that regular kratom consumption (at an average daily quantity of four glasses or with a mitragynine intake of 434.28 mg) can apparently increase QTc intervals but does not induce prolonged QTc intervals ( Leong Abdullah et al, 2021 ). However, this study was limited in that it lacked serum mitragynine analysis.…”

Section: Resultsmentioning

confidence: 93%

“…So far, only one study has evaluated electrocardiogram (ECG) findings related to regular kratom users (human subjects) without a history of polysubstance use or significant health problems ( Leong Abdullah et al, 2021 ). This cross-sectional study compared ECG findings between regular kratom users who consumed kratom daily and a control group.…”

Section: Resultsmentioning

confidence: 99%

“…A few case reports also speculatively suggested that kratom consumption may have induced ventricular arrhythmia, particularly ventricular tachycardia and fibrillation, resulting in cardiopulmonary arrest. However, the findings of a recent study demonstrated that regular kratom consumption (the ingestion of a brewed kratom decoction) appeared to increase QTc intervals but did not induce a prolonged QTc interval or torsades de pointes ( Leong Abdullah et al, 2021 ). Similarly, data from the national poison data system and autopsy reports of mortality cases indicated that conduction defects and cardiac arrhythmia were, indeed, rare.…”

Section: Discussionmentioning

confidence: 97%

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The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review

Abdullah

Singh

2021

Front. Pharmacol.

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Background: Kratom or Mitragyna speciosa (Korth.) has received overwhelming attention recently due to its alleged pain-relieving effects. Despite its potential therapeutic value, kratom use has been linked to many occurrences of multiorgan toxicity and cardiotoxicity. Accordingly, the current narrative review aimed to provide a detailed account of kratom’s adverse cardiovascular effects and cardiotoxicity risk, based on in vitro studies, poison center reports, coroner and autopsy reports, clinical case reports, and clinical studies.Methods: An electronic search was conducted to identify all research articles published in English from 1950 to 2021 using the major research databases, such as Google Scholar, Web of Science, PubMed, Scopus, Mendeley, EMBASE, Cochrane Library, and Medline. We then analyzed the literature’s discussion of adverse cardiovascular effects, toxicity, and mortality related to kratom use.Results: Our findings revealed that, although in vitro studies have found kratom preparations’ most abundant alkaloid—mitragynine—to cause a prolonged QTc interval and an increased risk of torsades de pointes, a clinical study examining humans’ regular consumption of kratom did not report such a risk. However, this latter study did show that regular kratom use could induce an increased QTc interval in a dose-dependent manner. A few case reports also highlighted that kratom consumption is associated with ventricular arrhythmia and cardiopulmonary arrest, but this association could have ensued when kratom was co-administered with another substance. Similarly, analyses of national poison data showed that kratom’s most common adverse acute cardiovascular effects include tachycardia and hypertension. Meanwhile, coroner and autopsy reports indicated that kratom’s cardiovascular sequelae encompass coronary atherosclerosis, myocardial infarction, hypertensive cardiovascular disease, left ventricular hypertrophy, cardiac arrhythmia, cardiomegaly, cardiomyopathy, focal band necrosis in the myocardium, and myocarditis. Given the available data, we deduced that all cardiac eventualities reported in the literature could have been compounded by polysubstance use and unresolved underlying medical illnesses.Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion, and further studies are still necessary to address this issue.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

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The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review

Abdullah

Singh

2021

Front. Pharmacol.

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“…In addition, in vitro studies on human induced pluripotent stem cell-derived cardiomyocytes indicated that mitragynine, the most abundant psychoactive alkaloid in kratom extract, is capable of prolonging the action potential duration of cardiomyocytes and increased the risk of prolonged QTc interval and torsades de pointes ( Lu et al, 2014 ). This was followed by a recent study of Electrocardiogram (ECG) in Malaysian subjects which highlighted that regular kratom use may increase the risk of borderline QTc interval [431–450 ms; ( Leong Abdullah et al, 2021 )]. Given the cardiovascular risk, Leong Abdullah et al (2021) study was limited by the absence of the serum mitragynine analysis in regular kratom users and cardiac pathology was not examined with echocardiogram.…”

Section: Introductionmentioning

confidence: 99%

“…This was followed by a recent study of Electrocardiogram (ECG) in Malaysian subjects which highlighted that regular kratom use may increase the risk of borderline QTc interval [431–450 ms; ( Leong Abdullah et al, 2021 )]. Given the cardiovascular risk, Leong Abdullah et al (2021) study was limited by the absence of the serum mitragynine analysis in regular kratom users and cardiac pathology was not examined with echocardiogram. Hence, we conducted this case series to fill the research gap by examining the cardiovascular functioning with electrocardiogram and echocardiogram, and serum mitragynine analysis was performed among regular kratom users in its traditional settings in Malaysia.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Cardiovascular Functioning Among Regular Kratom (Mitragyna speciosa Korth) Users: A Case Series

Abdullah

Singh

2021

Front. Pharmacol.

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Multiorgan toxicities have been extensively reported in kratom (Mitragyna speciosa Korth) users in Western countries but not in Southeast Asia. Existing literature argued that this discrepancy may be due to underreporting of kratom-related toxicity cases in Southeast Asia. Hence, this case series filled the research gap by clinically assessing the cardiovascular functioning and serum mitragynine level of regular kratom users in its traditional settings in Malaysia. Nine regular kratom users without history of polysubstance use were recruited from the same community via snowball sampling and were subjected to electrocardiogram (ECG) and echocardiogram assessments. Serum mitragynine analysis was also performed by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The mean serum mitragynine level was 10.3 mg/L (SD = 6.9) and ranged from 2.5 mg/L to 22.4 mg/L. Those who consumed an average daily quantity of four or more glasses of brewed kratom juice (p = 0.045) and those who had prolonged QTc intervals (p = 0.017) had significantly higher serum mitragynine level. Echocardiographic findings of all the respondents were normal except one reported left ventricular hypertrophy and another had trivial tricuspid regurgitation with pulmonary artery systolic pressure (PASP) of 10 + 5 mmHg. Regular kratom use without concomitant use of other illicit substances may not provoke any risk of cardiovascular impairment or toxicity except for prolonged QTc interval, which appeared to be dose dependent. However, as this study was limited by a small sample size, future studies with larger sample size are warranted to confirm our findings.

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A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans

Prevete

Kuypers

Theunissen

et al. 2021

Human Psychopharmacology

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Introduction: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption.Objective: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. Methods: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. Results: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal).Conclusions: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.

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Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls

Cited by 23 publications

References 37 publications

The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review

The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review

Assessment of Cardiovascular Functioning Among Regular Kratom (Mitragyna speciosa Korth) Users: A Case Series

A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans

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