Conversion of ibogaine to its active metabolite noribogaine is primarily mediated by the CYP2D6 enzyme. In a study of 21 healthy subjects given a single 20 mg oral dose of ibogaine after 6 days of pretreatment with either placebo or the CYP2D6 inhibitor paroxetine, those pretreated with paroxetine showed rapid absorption of ibogaine, with detectable levels lasting up to 72 hours and an elimination half-life of 10.2 hours. Noribogaine exposure was similar between groups, but the active moiety (ibogaine plus noribogaine) exposure was about 2-fold higher in paroxetine-pretreated subjects. CYP2D6 phenotype correlated strongly with ibogaine AUC and Cmax. The findings suggest genotyping patients before ibogaine treatment and halving the dose in CYP2D6 poor metabolizers to ensure safety.
A single 20mg dose of ibogaine had minimal influence on psychological tests and mood ratings in healthy male volunteers. The ability to selectively ignore distracting spatial information showed some evidence of modulation, but only in the less challenging condition, raising questions about reliability. No stimulant effects were identified. The study assessed relationships between changes in test scores and concentrations of active moiety (the sum of molar noribogaine and ibogaine concentrations), but future research is needed to confirm whether these concentrations impact selective attention abilities while leaving other cognitive functions and mood state unaffected.