Long-lasting ibogaine protection against NMDA-induced convulsions in mice.

A single dose of ibogaine in mice produces a complex, long-lasting pattern of modulation of NMDA receptors, a brain receptor type involved in addiction. Ibogaine inhibited convulsions induced by NMDA at 24 and 72 hours after treatment, and binding to NMDA receptors was also significantly decreased at those times. No effects were seen at 30 minutes or 48 hours. This sustained, non-continuous modulation may underlie ibogaine's ability to reduce withdrawal and craving for extended periods after a single dose.

Study at a glance

Abstract

Ibogaine, a putative antiaddictive drug, is remarkable in its apparent ability to downgrade withdrawal symptoms and drug craving for extended periods of time after a single dose. Ibogaine acts as a non-competitive NMDA receptor antagonist, while NMDA has been implicated in long lasting changes in neuronal function and in the physiological basis of drug addiction. The purpose of this study was to verify if persistent changes in NMDA receptors could be shown in vivo and in vitro after a single administration of ibogaine. The time course of ibogaine effects were examined on NMDA-induced seizures and [3H] MK-801 binding to cortical membranes in mice 30 min, 24, 48, and 72 h post treatment. Ibogaine (80 mg/kg, ip) was effective in inhibiting convulsions induced by NMDA at 24 and 72 hours post administration. Likewise, [3H] MK-801 binding was significantly decreased at 24 and 72 h post ibogaine. No significant differences from controls were found at 30 min or 48 h post ibogaine. This long lasting and complex pattern of modulation of NMDA receptors prompted by a single dose of ibogaine may be associated to its antiaddictive properties.