Ibogaine as a double-edged sword: Developmental cardiotoxicity and neurobehavioral alterations in zebrafish

Ibogaine has attracted increasing attention as a potential treatment for substance use disorders; however, its clinical application remains limited by well-documented cardiotoxicity, and its safety during early development is poorly understood. Here, we investigated the developmental cardiotoxic and neurobehavioral effects of ibogaine using zebrafish embryos and larvae as a translational model. Ibogaine induced early-onset bradycardia at concentrations as low as 100 ng/mL and pericardial edema at concentrations of 500 ng/mL, indicating both functional and morphological cardiac impairment. In parallel, ibogaine disrupted neurobehavioral endpoints, including increased embryonic motor activity, altered locomotor patterns and exploratory behavior in larvae. Notably, behavioral alterations emerged at lower concentrations than overt morphological toxicity, suggesting that neurodevelopmental endpoints may be more sensitive indicators of ibogaine exposure. These findings demonstrate that ibogaine affects multiple physiological systems during early development and highlight potential risks associated with its use in vulnerable populations. Given its increasing therapeutic interest, our results underscore the need for careful safety evaluation, particularly regarding developmental exposure and cardiac liability.