NYU Conference on Ibogaine Nov 5-6, 1999

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MECHANISMS OF ANTI-ADDICTION ACTIONS OF IBOGAINE

Stanley D. Glick, Isabelle M. Maisonneuve and Sandra M. Pearl
Department of Pharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA

Ibogaine, an alkaloid extracted from Tabernanthe iboga, is being studied as a potential long-acting treatment for both opioid and simulant abuse. Studies in this laboratory have used animal models to characterize ibogaine's interactions with opioids and stimulants, and to investigate mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can decrease both morphine and cocaine self-administration for several days in some rats. Acutely, both ibogaine and noribogaine decrease extracellular levels of dopamine in the nucleus accumbens of the rat brain. Ibogaine pretreatment (19 hours beforehand) blocks morphine induced dopamine release and morphine-induced locomotor hyperactivity while, in contrast, it enhances similar effects of stimulants (cocaine and amphetamine). Both ibogaine and noribogaine bind to kappa opioid and NMDA receptors. Ongoing studies in rats suggest that both kappa agonist and NMDA antagonist actions contribute to ibogaine's anti-addictive effects. Some effects (e.g., on morphine and cocaine self-administration, morphine induced hyperactivity, cocaine-induced increases in nucleus accumbens dopamine) are mimicked by a kappa agonist (U50,488) and/or a NMDA antagonist (MK-801). Moreover, a combination of a kappa antagonist and a NMDA agonist, but neither alone, will reverse several of Ibogaine's effects. We propose that ibogaine's long-term effects are mediated by slow release from fat tissue (where ibogaine is sequestered), conversion to noribogaine, and eventual binding of both ibogaine and noribogaine to kappa opiod and NMDA receptors. (Supported by USPHS DA03817)

Correspondence: Stanley D. Glick, MD; Chairman; Department of Pharmacology and Neuroscience A-136; Albany Medical College; 47 New Scotland Avenue; Albany, NY 12208, USA