Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin.
Deborah C. Mash, J K Staley, Michael H. Baumann, Richard B Rothman, W L Hearn
Life Sciences 1995 DOI: 10.1016/0024-3205(95)00273-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | Ibogaine 12-hydroxyibogamine |
| Topics | Ibogaine Serotonin |
| Citations | 108 |
| Key findings | 12-hydroxyibogamine, a metabolite of ibogaine, elevates extracellular serotonin by binding with high affinity to the serotonin transporter, while neither ibogaine nor its metabolite increase dopamine levels in the nucleus accumbens. |
Abstract
Ibogaine is a hallucinogenic indole with putative efficacy for the treatment of cocaine, stimulant and opiate abuse. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. We report here that 12-hydroxyibogamine, a primary metabolite of ibogaine, displays high affinity for the 5-HT transporter and elevates extracellular 5-HT. In radioligand binding assays, 12-hydroxyibogamine was 50-fold more potent at displacing radioligand binding at the 5-HT transporter than at the DA transporter. Ibogaine and 12-hydroxyibogamine were equipotent at the dopamine transporter. In vivo microdialysis was used to evaluate the acute actions of ibogaine and 12-hydroxyibogamine on the levels of DA and 5-HT. Administration of 12-hydroxyibogamine produced a marked dose-related elevation of extracellular 5-HT. Ibogaine and 12-hydroxyibogamine failed to elevate DA levels in the nucleus accumbens over the dose range tested. The elevation in synaptic levels of 5-HT by 12-hydroxyibogamine may heighten mood and attenuate drug craving. The effects of the active metabolite on 5-HT transmission may account in part for the potential of ibogaine to interrupt drug-seeking behavior in humans.