Abstract: Compositions and methods are provided to reduce opioid-related symptoms in a human patient of an exorphin selected from the group consisting of a gluteomorphin and a caseomorphin, comprising a physiologically effective amount of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase. Preferrably the caseomorphinase is dipeptidyl peptidase IV and the gluteomorphinase is tyrosinase or phenylalaninase.