Iboga interactions with psychomotor stimulants: panacea in the paradox?
Toxicon : official journal of the International Society on Toxinology – January 01, 2001
Source: PubMed
Summary
A promising insight reveals that certain natural compounds may combat stimulant addiction by reversing brain changes linked to craving. While initial observations suggested a paradox, new findings show that iboga agents, like ibogaine and 18-methoxycoronaridine, effectively block the heightened dopamine responses in the brain caused by chronic stimulant use. This reversal of neuroadaptations offers a positive mechanism for how these agents reduce drug self-administration in preclinical models, potentially alleviating compulsive drug-seeking behavior.
Abstract
Currently, no effective therapy has been approved for the treatment of addiction to stimulant drugs (e.g., cocaine, amphetamine and its methylated derivatives). However, preclinical studies indicate that the naturally-occurring indole alkaloid, ibogaine, and a synthetic iboga alkaloid congener, 18-methoxycoronaridine (18-MC), attenuate stimulant self-administration in laboratory animals. The in vivo pharmacological interactions between iboga agents and stimulant drugs are unclear. Ibogaine enhances the increase in accumbal dopamine produced by the acute administration of stimulant drugs. Consistent with these data, both ibogaine and 18-MC potentiate the expression of stimulant-induced motor behaviors in acute and chronic stimulant-treated animals. To account for the paradox between their effects on self-administration and motor behavior, we proposed that iboga agents interfere with stimulant self-administration by increasing sensitivity to their psychomotor-activating effects. However, this interpretation is contradicted by very recent observations that 18-MC is without effect on the dopamine response to acute cocaine and that both ibogaine and 18-MC block the expression of sensitized levels of dopamine in the nucleus accumbens produced by chronic cocaine administration. Thus, a positive relationship exists between the effects of iboga pretreatment on stimulant-induced dopamine sensitization and stimulant self-administration behavior. These data indicate that iboga agents might attenuate stimulant self-administration by reversing the neuroadaptations theoretically implicated in drug craving and compulsive drug-seeking behavior.