Ibogaine, a compound from the African shrub Tabernanthe iboga, did not alter pain relief (antinociception) produced by morphine, U-50,488H, or DPDPE in male Swiss-Webster mice when given 10 minutes before these opioids. Ibogaine alone had no effect on pain sensitivity. However, its metabolite noribogaine enhanced morphine's pain-relieving effect at doses of 40 and 80 mg/kg, particularly with a lower morphine dose (5 mg/kg). Noribogaine did not affect pain relief from U-50,488H or DPDPE. The authors conclude that ibogaine's reported ability to reduce drug self-administration likely does not involve direct interaction with multiple opioid receptors, but its metabolite noribogaine may interact with mu-opioid receptors to enhance morphine's effects.
Ibogaine, a compound from the African shrub Tabernanthe iboga, selectively blocks the development of tolerance to morphine's pain-relieving effect in male Swiss-Webster mice. Mice given morphine, U-50,488H, or DPDPE (agonists for mu-, kappa-, and delta-opioid receptors, respectively) twice daily for four days became tolerant to these drugs' antinociceptive effects. Ibogaine at 40 or 80 mg/kg, given before each morphine injection, prevented tolerance to morphine, but 20 mg/kg did not. Ibogaine did not affect tolerance to kappa- or delta-receptor agonists at any dose. The results suggest ibogaine specifically inhibits tolerance to mu-opioid receptor agonists.