Ibogaine, a putative anti-addictive agent, and its active metabolite noribogaine modulate morphine's pain-killing (antinociceptive) effects in rats, depending on timing and dose. When given 19 hours before morphine, ibogaine significantly reduced morphine's antinociception, but had no effect alone. In contrast, co-administration of ibogaine (1-40 mg/kg) with morphine increased antinociception in a dose-dependent manner. Co-administration of noribogaine (40 mg/kg) with morphine also enhanced antinociception, while noribogaine pretreatment (19 hours) had no effect. The findings indicate that ibogaine acutely potentiates morphine antinociception, likely through noribogaine, but the delayed inhibitory effect after 19 hours is not explained by noribogaine.
After a 20 mg/kg intravenous infusion in rats, ibogaine levels in plasma declined rapidly in a two-phase pattern, with an initial half-life of 7.3 minutes and a terminal half-life of 3.3 hours. Drug clearance was 5.9 L/h. Three hours after infusion, ibogaine concentrations in brain, liver, and kidney were 143–170 ng/g, but in adipose tissue the concentration was much higher at 3,328 ng/g. This sequestration in fat likely causes the drug to persist in the body longer than the terminal half-life suggests. The initial rapid disappearance from plasma may result from metabolic demethylation and redistribution to tissues.