A method for modulating tolerance to an opioid analgesic in a patient undergoing opioid analgesic therapy, the method comprising interrupting or administering concurrently with said opioid analgesic therapy an amount of noribogaine, noribogaine derivative, or pharmaceutically acceptable salt and/or solvate thereof that provides a therapeutic serum concentration of noribogaine. In some embodiments, the therapeutic average serum concentration is 50 ng/mL to 180 ng/mL, said concentration being sufficient to re-sensitize the patient to the opioid as an analgesic while maintaining a QT interval of less than about 500 ms during said treatment.