Ibogaine Induces Cardiotoxic Necrosis in Rats-The Role of Redox Processes.

Ibogaine, an alkaloid used in alternative addiction treatment, caused dose-dependent heart muscle cell death (necrosis) in rats 6 and 24 hours after a single oral dose of 1 or 20 mg/kg. This cardiotoxicity was not driven by inflammation. No consistent changes in antioxidant defenses or oxidative damage markers were observed, leaving the role of oxidative stress in ibogaine-induced heart damage unclear. The findings help explain the often-fatal cardiac side effects seen in humans using ibogaine, but definitive conclusions about redox processes require further study.

Study at a glance

Abstract

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.