Evidence for roles of kappa-opioid and NMDA receptors in the mechanism of action of ibogaine.

Ibogaine, a substance with potential anti-addictive properties, works through two brain receptor systems: kappa-opioid and NMDA. In rats, blocking kappa-opioid receptors and activating NMDA receptors together partially prevented ibogaine's ability to reduce morphine self-administration and to counteract morphine-induced hyperactivity. Either treatment alone, or in combination, also blocked ibogaine's effects on dopamine release and metabolism in the striatum. These results suggest that ibogaine's anti-addictive effects rely on both its kappa-opioid agonist and NMDA antagonist actions.

Study at a glance

Abstract

Ibogaine, a putatively anti-addictive alkaloid, binds to kappa-opioid and NMDA receptors. In the present study we investigated the roles of kappa-opioid and NMDA actions in mediating ibogaine's (40 mg/kg, i.p.) behavioral and neurochemical effects in rats. A combination of a kappa-opioid antagonist (norbinaltorphimine, 10 mg/kg, s.c.) and a NMDA agonist (NMDA, 20 mg/kg, i.p.) partially prevented ibogaine-induced inhibition of intravenous morphine self-administration and ibogaine-induced antagonism of morphine-induced locomotor stimulation. The combination, as well as norbinaltorphimine and NMDA alone, blocked the acute effects of ibogaine on dopamine release and metabolism in the striatum. The data suggest that both kappa-opioid agonist and NMDA antagonist actions of ibogaine contribute to its putative anti-addictive effects.