The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients

Summary & key facts

In 14 people with opioid use disorder who each received a single 10 mg/kg dose of ibogaine, researchers measured blood levels of ibogaine and its metabolites over 24 hours and linked those levels to side effects. They found large differences between people in how fast ibogaine was cleared, and that this clearance was strongly tied to each person's CYP2D6 genotype. Higher ibogaine levels were linked to longer QTc on ECG and to cerebellar (ataxia) effects, while noribogaine levels did not show those links. The authors say future work should test lower doses or dosing based on CYP2D6 genotype.

Key facts:

• The study enrolled 14 patients with opioid use disorder who received one oral dose of 10 mg/kg ibogaine hydrochloride and had blood measurements for 24 hours.
• Ibogaine clearance depended strongly on CYP2D6 genotype: estimated basic clearance at a CYP2D6 activity score (AS) of 0 was 0.82 L/h, and clearance increased by 30.7 L/h for each 1-point increase in AS (relationship p < 0.001).
• Ibogaine plasma concentrations correlated with QTc prolongation and cerebellar effects (Spearman correlations reported as statistically significant, p < 0.03), while noribogaine did not show significant correlations with QTc (p = 0.109) or
• The relationship between ibogaine concentration and QTc was modeled best by a sigmoid Emax type curve, meaning QTc lengthening rose with concentration up to a maximum effect.
• Neither ibogaine nor noribogaine concentrations were correlated with the severity of opioid withdrawal symptoms in this study.
• The authors reported that ibogaine pharmacokinetics were highly variable between participants and concluded that future studies should explore lower doses and/or individualized dosing by CYP2D6 genotype.

Abstract

The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

Topics

Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Treatment of Major Depression

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

Anesthesia CYP2D6 Cytochrome P450 Internal medicine Medicine Metabolism Opioid Opioid use disorder Pharmacology QT interval Receptor