Ibogaine: Therapeutic Potential, Cardiac Safety, and Translational Perspectives in the Treatment of Substance Use Disorders—A Scoping Review

Substance Use Disorder (SUD) causes about 600,000 deaths yearly, mainly from opioid use. Current treatments are limited because they target only isolated brain processes and fail to address key mechanisms like glutamatergic hyperactivity, low dopamine in reward pathways, and dysfunction in control networks, leading to high relapse rates. Ibogaine, an alkaloid from the Tabernanthe iboga plant, has re-emerged as a candidate due to its ability to modulate multiple pathways linked to addiction. However, its clinical use is hindered by fragmented evidence, lack of regulatory frameworks, inconsistent product quality, and cardiac safety concerns. This scoping review synthesizes preclinical and clinical data on ibogaine for SUD, focusing on withdrawal, craving, dose-response, and cardiac risks, and outlines conditions for further investigation.

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Abstract

Substance Use Disorder (SUD) constitutes a major and persistent global public health burden, accounting for approximately 600,000 deaths annually, largely driven by opioid use. Despite substantial advances in addiction neuroscience, currently approved therapeutic strategies remain limited in efficacy, as they predominantly target isolated neurobiological processes and fail to concurrently address core mechanisms such as glutamatergic hyperactivity, mesolimbic hypodopaminergic, and dysfunction of cortical and executive control networks. This mechanistic fragmentation contributes to persistently high relapse rates and underscores the need for integrative and multitarget therapeutic approaches. Within this context, ibogaine has re-emerged as a clinical candidate due to its distinctive multimodal neuropharmacological profile and its reported capacity to modulate multiple pathways implicated in addictive behaviours. However, the clinical translation of ibogaine remains substantially constrained by fragmented and heterogeneous evidence, the absence of regulatory frameworks in several jurisdictions, limited phytochemical validation and standardization of available formulations, and unresolved concerns regarding cardiac safety. This scoping review critically synthesizes the available preclinical and clinical literature on ibogaine in the treatment of SUD, with particular emphasis on reported effects on withdrawal symptoms and craving, dose-response relationships, and the occurrence of cardiac adverse events. By clarifying the current state of the evidence and delineating key translational constraints, this review defines the conditions under which ibogaine, an indole alkaloid isolated from Tabernanthe iboga Baill. (Apocynaceae), may warrant continued investigation. The hypothesis of a neurobiological "reset", supported by emerging preclinical and clinical data, positions ibogaine as a compound of relevance in addiction research and highlights the need for rigorous pharmacological, toxicological, and regulatory evaluation to inform safer and more standardized clinical pathways.