Christopher Wu, Sebastian Gastelum, Jonathan Al-Fakhoury, Nathaniel Bowes, Karam Khamashta, John Crupi, William H Frishman, Wilbert S Aronow
Mitragyna speciosa (kratom) is an increasingly used product marketed for pain relief, mood enhancement, stimulation, and self-management of opioid withdrawal. Its principal alkaloids, mitragynine and 7-hydroxymitragynine, interact with μ-opioid, adrenergic, serotonergic, and dopaminergic receptors and may also influence cardiac ion channels and autonomic regulation. Experimental studies demonstrate inhibition of the human ether-à-go-go-related gene potassium channel, delayed ventricular repolarization, and potential effects on sodium and G-protein-coupled inwardly rectifying potassium channels. Clinically reported cardiovascular manifestations include tachycardia, hypertension, QTc prolongation, Brugada-pattern electrocardiographic abnormalities, ventricular arrhythmias, cardiac arrest, and possible myocardial or vascular injury. Kratom may also interact with cardiovascular medications through inhibition of cytochrome P450 enzymes and drug transporters, potentially altering exposure to β-blockers, antiarrhythmics, calcium-channel blockers, anticoagulants, and digoxin. Although preliminary studies have suggested possible anti-inflammatory, metabolic, antioxidant, and opioid-substitution benefits, these findings remain largely preclinical or observational. Interpretation of the available literature is limited by heterogeneous product composition, polysubstance exposure, inconsistent dosing, and reliance on case reports, toxicologic surveillance, and pharmacovigilance data. Greater clinical awareness and prospective research using standardized kratom preparations are needed to clarify its cardiovascular risks, potential benefits, and clinically relevant drug interactions.