Molecules
January 29, 2015
Xaver Koenig, Karlheinz Hilber
123 citations
Ibogaine, a plant-derived indole alkaloid, shows promise for treating addiction by reducing drug craving and preventing relapse in both animals and humans, yet it is not a licensed therapeutic and raises safety concerns. Alarming reports of life-threatening complications and sudden deaths linked to ibogaine use have accumulated, likely due to its tendency to cause cardiac arrhythmias. This review summarizes current knowledge on ibogaine's cardiovascular effects and assesses the cardiac risks of its use in anti-addiction therapy. It also considers 18-methoxycoronaridine (18-MC), a less toxic ibogaine derivative with anti-addictive properties.
Addiction biology
March 1, 2014
Xaver Koenig, Michael Kovar, Stefan Boehm et al.
50 citations
Therapeutic concentrations of ibogaine, an alkaloid from the African shrub Tabernanthe iboga used in alternative medicine for its anti-addictive properties, reduce currents through human ether-a-go-go-related gene potassium channels. This provides a mechanism by which ibogaine may generate life-threatening cardiac arrhythmias, consistent with anecdotal evidence that it can disturb heart rhythm.
Toxicology and applied pharmacology
December 1, 2013
Xaver Koenig, Michael Kovar, Lena Rubi et al.
46 citations
Ibogaine, a plant alkaloid used to treat drug addiction despite not being licensed, inhibits hERG potassium channels at low micromolar concentrations, which could disturb heart rhythm. At higher concentrations, it also reduces sodium and calcium currents. Its congener 18-MC blocks these ion channels with less potency. Unexpectedly, ibogaine did not prolong action potentials in guinea pig cardiomyocytes at low concentrations, and higher concentrations shortened them, likely because calcium channel inhibition counteracts hERG blockade effects. However, computer modeling of human ventricular cells suggested ibogaine does prolong the action potential in humans. The authors conclude therapeutic concentrations may prolong the QT interval, potentially leading to cardiac arrhythmias.
The Journal of pharmacology and experimental therapeutics
February 1, 2014
Patrick Thurner, Anna Stary-Weinzinger, Hend Gafar et al.
41 citations
Ibogaine, a psychoactive alkaloid used to treat addiction, can cause dangerous heart rhythm problems by blocking hERG potassium channels. Experiments on mammalian kidney cells expressing hERG channels showed that block occurred from either side of the cell membrane and depended on pH. Block happened only when channels were activated, not when resting. Stronger depolarizations increased block speed and extent. The drug shifted channel activation and inactivation to more negative voltages, slowed deactivation, and accelerated inactivation. Mutations Y652A and F656A reduced ibogaine's potency, but an inactivation-deficient mutant remained sensitive. Molecular docking suggested binding inside the channel cavity regardless of ibogaine's protonation state. Kinetic modeling indicated preferential binding to open and inactivated states.
Cardiovascular toxicology
April 1, 2017
Lena Rubi, Daniel Eckert, Stefan Boehm et al.
18 citations
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.
The International Journal of Neuropsychopharmacology
December 3, 2021
Benjamin Hackl, Hannes Todt, Helmut Kubista et al.
11 citations
Psilocybin, the hallucinogen in magic mushrooms, is being studied for psychiatric disorders, but safety concerns arose after reports of cardiac events and QT interval prolongation linked to its metabolite psilocin. Clinical concentrations of psilocin do not significantly inhibit the hERG potassium channel, a key risk factor for adverse cardiac effects. Therefore, hERG channel blockage by psilocin is not responsible for psilocybin-associated cardiotoxicity.
BMC Pharmacology
September 5, 2011
Michael Kovar, Xaver Koenig, Ágnes K. Mike et al.
5 citations
Ibogaine, an alkaloid from the African shrub Tabernanthe iboga, has psychoactive properties and is being studied as a potential treatment for opioid, stimulant, alcohol, and nicotine addiction. However, its complex interactions with many cellular targets raise significant safety concerns. Beyond neurotoxic effects, ibogaine may harm the heart: several sudden deaths after use have been reported, possibly due to cardiac arrhythmias. In one case, a woman experienced a severely prolonged QT interval and ventricular tachyarrhythmias after taking ibogaine.
BMC Pharmacology and Toxicology
September 1, 2012
Xaver Koenig, Michael Kovar, Lena Rubi et al.
Ibogaine, a plant alkaloid used in alternative medicine for addiction despite not being a licensed therapeutic, can disturb heart rhythm. At therapeutic concentrations it inhibits hERG potassium channels, which can cause life-threatening arrhythmias. This study examined ibogaine and its analog 18-methoxycoronaridine (18-MC) on cardiac ion channels using patch clamp techniques and computer simulations. Ibogaine reduced hERG currents at low micromolar concentrations (IC50, 4 µM) and, at higher concentrations, also inhibited sodium channels. 18-MC was less potent. In guinea-pig cardiomyocytes, ibogaine did not prolong the action potential at low concentrations; higher concentrations shortened it. Computer modeling suggested calcium channel blockade counteracts hERG inhibition's prolonging effect. Ibogaine is potentially proarrhythmic but may also have antiarrhythmic properties.