The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.
Level 4 - case-series / case-control
Single-arm pharmacokinetic and pharmacodynamic study in 14 patients without a control group
PubMed 38519421 · doi:10.1177/02698811241237873
What was done
Fourteen patients with opioid use disorder undergoing detoxification received a single oral dose of 10 mg/kg ibogaine hydrochloride. Plasma concentrations of ibogaine, noribogaine, and noribogaine glucuronide were measured over 24 hours alongside CYP2D6 genotyping. Non-linear mixed-effects modeling and correlation analyses assessed the relationships between drug levels, corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity.
What was found
Ibogaine pharmacokinetics varied widely and correlated significantly with CYP2D6 genotype (p < 0.001). Ibogaine baseline clearance at a CYP2D6 activity score (AS) of 0 was 0.82 L/h, increasing by 30.7 L/h for each point increase in AS. Ibogaine plasma concentrations correlated significantly with QTc prolongation (sigmoid Emax model; Spearman p < 0.03) and cerebellar effects (p < 0.03). In contrast, noribogaine concentrations did not correlate with QTc (p = 0.109) or cerebellar effects (p = 0.668). Neither compound correlated with opioid withdrawal symptom severity.
Why it matters
These findings suggest that cardiac and cerebellar side effects are driven by parent ibogaine rather than its metabolite noribogaine, highlighting CYP2D6 genotype-informed dosing as a potential strategy to reduce toxicity risks.
Limits
The study is limited by a small sample size (n = 14) and lack of a control group. Monitoring was restricted to 24 hours, and the study did not evaluate long-term safety, relapse rates, or sustained therapeutic efficacy.