DARK Classics in Chemical Neuroscience: Ibogaine.
Level 5 - mechanism / opinion, no new human data
Narrative review summarizing historical, preclinical, and mechanistic literature with no new primary human trial data.
PubMed 30216039 · doi:10.1021/acschemneuro.8b00294
What was done
This narrative review synthesizes the historical, pharmacological, and toxicological literature on ibogaine. It evaluates historical human usage, behavioral pharmacology in animal self-administration models (opiates, cocaine, amphetamines, nicotine), receptor/transporter binding profiles, mechanisms of toxicity, and the development of structural analogs such as 18-methoxycoronaridine (18-MC).
What was found
The abstract reports no quantitative values or effect sizes. It notes that behavioral studies in animal models demonstrate ibogaine blunts self-administration of opiates, cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities across diverse receptors and transporters, with antiopiate effects linked to nicotinic acetylcholine receptor modulation. At micromolar concentrations, ibogaine causes neurotoxicity and cardiotoxicity, including fatal cardiac arrest. The analog 18-MC acts as an α3β4 nicotinic receptor modulator that retains anticraving properties with fewer reported adverse effects.
Why it matters
This review highlights the mechanistic basis and serious cardiotoxic limitations of ibogaine, framing why modern drug development has shifted to safer analogs for substance use disorders.
Limits
The abstract describes a narrative overview rather than a systematic review or primary clinical trial. Efficacy claims for addiction interruption are based largely on historical reports and animal self-administration models. No quantitative data, sample sizes, or toxicity thresholds are reported in the abstract.
Cited by
- supports Animal studies show that animals do not self-administer ibogaine.