A single dose of ibogaine (10 mg/kg) in 14 patients with opioid use disorder caused an average QTc prolongation of 95 ms (range 29–146 ms); half of the subjects reached a QTc over 500 ms. No life-threatening cardiac events occurred, but severe temporary ataxia (inability to walk without support) was universal. Withdrawal and psychomimetic effects were mostly manageable; 11 of 14 patients did not return to morphine within 24 hours. The findings indicate that ibogaine induces clinically relevant but reversible QTc prolongation, bradycardia, and severe cerebellar toxicity.
Ibogaine, a hallucinogenic drug being studied for opioid use disorder, shows highly variable pharmacokinetics strongly linked to CYP2D6 genotype. In 14 patients given a single 10 mg/kg dose, ibogaine clearance increased by 30.7 L/h per point of CYP2D6 activity score, from a baseline of 0.82 L/h. Higher ibogaine plasma concentrations correlated significantly with QTc prolongation and cerebellar ataxia, while noribogaine did not. Neither ibogaine nor its metabolite correlated with opioid withdrawal severity. These findings suggest that cardiac and neurological side effects are driven more by ibogaine itself, and that lower or genotype-personalized dosing may improve safety.