How toxic is ibogaine?

Area of Science:

• Pharmacology
• Neuroscience
• Toxicology

Background:

• Ibogaine, a psychoactive alkaloid from *Tabernanthe iboga*, is used for addiction treatment.
• Despite its use, ibogaine's toxicity raises significant safety concerns.

Purpose of the Study:

• To review the pharmacokinetics, pharmacodynamics, mechanisms of action, and toxicity of ibogaine.
• To synthesize current knowledge on ibogaine's effects and risks.

Main Methods:

• Literature search of PubMed using keywords related to ibogaine's effects and toxicity.
• Analysis of 382 unique references, with a focus on 156 human data studies and 14 toxicological case reports.

Main Results:

• Ibogaine and its metabolite noribogaine interact with multiple neurotransmitter systems, including NMDA, opioid, and sigma receptors.
• Potential neurotoxicity observed in rats, possibly dose-dependent, with noribogaine potentially less neurotoxic than ibogaine.
• Cardiotoxicity linked to hERG channel blockade, leading to QT interval prolongation, arrhythmias, and sudden cardiac arrest; 27 fatalities reported.
• CYP2D6 metabolism influences ibogaine concentrations, posing risks for drug-drug interactions.

Conclusions:

• Ibogaine and its derivatives are still used by alternative therapists and individuals for addiction treatment.
• Use outside of medical supervision presents risks, with potential for increased ibogaine-related deaths, especially in those with cardiac conditions or on concurrent medications.