Iboga interactions with psychomotor stimulants: panacea in the paradox?

Currently, no effective therapy has been approved for the treatment of addi ction to stimulant drugs (e.g., cocaine, amphetamine and its methylated der ivatives). However, preclinical studies indicate that the naturally-occurri ng indole alkaloid, ibogaine, and a synthetic iboga alkaloid congener, 18-m ethoxycoronaridine (18-MC), attenuate stimulant self-administration in labo ratory animals. The in vivo pharmacological interactions between iboga agen ts and stimulant drugs are unclear. Ibogaine enhances the increase in accum bal dopamine produced by the acute administration of stimulant drugs. Consi stent with these data, both ibogaine and 18-MC potentiate the expression of stimulant-induced motor behaviors in acute and chronic stimulant-treated a nimals. To account for the paradox between their effects on self-administra tion and motor behavior, we proposed that iboga agents interfere with stimu lant self-administration by increasing sensitivity to their psychomotor-act ivating effects. However, this interpretation is contradicted by very recen t observations that 18-MC is without effect on the dopamine response to acu te cocaine and that both ibogaine and 18-MC block the expression of sensiti zed levels of dopamine in the nucleus accumbens produced by chronic cocaine administration. Thus, a positive relationship exists between the effects o f iboga pretreatment on stimulant-induced dopamine sensitization and stimul ant self-administration behavior, These data indicate that iboga agents mig ht attenuate stimulant self-administration by reversing the neuroadaptation s theoretically implicated in drug craving and compulsive drug-seeking beha vior. (C) 2000 Elsevier Science Ltd. All rights reserved.