Intravenous nicotine infusions in rats increase extracellular dopamine in a dose- and order-dependent manner, with acute tolerance appearing when infusions are spaced one hour apart but not when spaced three hours apart. Pretreatment with ibogaine 19 hours before nicotine attenuates this dopamine increase, suggesting ibogaine may reduce nicotine's rewarding effect.
Ibogaine and two related compounds (noribogaine and 18-methoxycoronaridine) both inhibit and later enhance cocaine-induced hyperactivity in rats, depending on timing. When given 1 hour before cocaine, all three agents reduced the hyperactivity caused by cocaine. When given 19 hours before cocaine, they instead amplified it. These opposite, time-dependent effects explain conflicting findings in earlier research and were not caused by the drugs' own effects on movement.