Ibogaine neurotoxicity: a re-evaluation.

High doses of ibogaine (100 mg/kg or repeated doses) cause degeneration of cerebellar Purkinje cells in rats, particularly in lobules 5 and 6, which may lead to motor deficits in the head and upper extremities. In contrast, a lower dose (40 mg/kg) that is effective in reducing morphine and cocaine self-administration produces no more degeneration than saline. The findings suggest that ibogaine's degenerative effects and its anti-addictive properties stem from different mechanisms of action.

Study at a glance

Abstract

Ibogaine is claimed to be an effective treatment for opiate and stimulant addiction. O'Hearn and Molliver, however, showed that ibogaine causes degeneration of cerebellar Purkinje cells in rats. The present study re-examined cerebellar responses to the high doses of ibogaine used by O'Hearn and Molliver (100 mg/kg or 3 x 100 mg/kg) and sought to determine whether a lower dose (40 mg/kg), one effective in reducing morphine and cocaine self-administration, produced similar responses. Purkinje cell degeneration was evaluated with a Fink-Heimer II stain, and enhanced glial cell activity with an antibody to glial fibrillary acidic protein. Every rat treated with the high dose of ibogaine displayed clear evidence of Purkinje cell degeneration. The degeneration consistently occurred in the intermediate and lateral cerebellum, as well as the vermis. Purkinje cells in lobules 5 and 6 were particularly susceptible. Given the response properties of cells in these lobules, this finding suggests any long-term motor deficits produced by ibogaine-induced degeneration should preferentially affect the head and upper extremity. In marked contrast, rats given the smaller dose of ibogaine displayed no degeneration above the level seen in saline-treated animals. When combined with information on other compounds, these data suggest that the degenerative and "anti-addictive' properties of ibogaine reflect different actions of the drug.