Ibogaine hydrochloride reduced the locomotor stimulation caused by low-to-moderate doses of d-amphetamine in male mice, an effect that lasted two days, but did not block the effect of a high dose. A lower dose of ibogaine was ineffective. Ibogaine decreased striatal dopamine levels by 30%, while d-amphetamine increased them by 26%. In rats, ibogaine pretreatment paradoxically increased d-amphetamine-induced locomotion, indicating species specificity. The findings suggest ibogaine can modulate dopamine-related behavioral effects in a dose- and species-dependent manner.
Ibogaine increases the release of dopamine from mouse striatum in a concentration-dependent way, primarily from the cytoplasmic pool rather than from vesicles, and this release is not regulated by presynaptic autoreceptors. The effect is reduced by dopamine uptake inhibitors but not by removing calcium or blocking sodium channels. Ibogaine does not affect dopamine uptake or retention. The dopamine-releasing action may contribute to its hallucinogenic effects observed in African ritual practices.