Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study.

Ibogaine, a substance claimed to reduce drug craving, alters brain dopamine systems for longer than it remains in the body. In rats, an acute injection of ibogaine decreased dopamine levels in the striatum, increased them in the prefrontal cortex, and had no effect in the nucleus accumbens. Nineteen hours later, dopamine remained lower in the striatum, and metabolite levels were reduced across all three brain regions. When given 19 hours before a low dose of morphine, ibogaine prevented the usual dopamine increase caused by morphine. A high dose of morphine alone did not raise dopamine, making it unclear whether ibogaine blocked or enhanced the low-dose effect. Overall, ibogaine produces lasting changes in brain dopamine systems and alters their response to morphine.

Study at a glance

Abstract

Ibogaine, an indolalkylamine, has been claimed to be effective in abolishing drug craving in heroin and cocaine addicts. The present study used in vivo microdialysis to determine the effects of ibogaine on extracellular levels of dopamine (DA) and its metabolites and the effects of ibogaine pretreatment on morphine stimulation of brain DA systems. Acutely, ibogaine (40 mg/kg i.p.) decreased extracellular DA levels in the striatum, increased them in the prefrontal cortex and had no significant effects in the nucleus accumbens. Nineteen hours after ibogaine injection. DA levels were still decreased in the striatum and the metabolite levels were lower in all three regions. When injected 19 h prior to a morphine challenge (5 mg/kg i.p.), ibogaine (40 mg/kg, i.p.) prevented the rise in DA levels in all three regions normally observed after a morphine injection. A high dose of morphine (30 mg/kg i.p.), administered alone, produced no increase in extracellular DA levels; it is therefore unclear whether ibogaine antagonized or potentiated the effects of the lower dose of morphine. Regardless of the nature of this interaction, it appears that ibogaine affects brain DA systems for a period of time that exceeds its elimination from the body and, during this time, alters the responses of these systems to morphine.