Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

The anti-addiction drug ibogaine and its main metabolite noribogaine slow action potential repolarization in human heart cells, providing the first experimental proof that ibogaine poses a risk of cardiac arrhythmias for humans. Using whole-cell patch clamp recordings on human ventricular-like cardiomyocytes derived from induced pluripotent stem cells, therapeutic concentrations of both substances significantly retarded repolarization. This explains the delayed incidence of cardiac adverse events observed several days after ibogaine intake. The findings suggest that ibogaine may prolong the QT interval in the electrocardiogram, leading to life-threatening arrhythmias and sudden death.

Study at a glance

Abstract

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.