A novel synthetic compound, 18-methoxycoronaridine (MC), reduces morphine and cocaine self-administration in rats without the tremors and cerebellar toxicity seen with ibogaine. In acute tests, MC decreased drug intake but did not affect bar-press responding for water. In some rats, a single 40 mg/kg dose of MC produced prolonged decreases in morphine or cocaine intake lasting days or weeks. MC showed no tremorigenic effect, and a high dose of 100 mg/kg caused no cerebellar toxicity. Like ibogaine, MC lowered extracellular dopamine levels in the nucleus accumbens. MC appears to be a safer ibogaine-like agent potentially useful for treating addiction.
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.