Silverman BL, et al. - The safety and effect on weight of a combination of olanzapine (OLZ; 10 mg) and the opioid modulator samidorphan (SAM; 5 mg) in comparison to OLZ alone in healthy, male normal weight volunteers were investigated in this present phase 1, proof of concept, multicenter, randomized, double-blind, placebo-controlled study. Compared to OLZ alone, OLZ + SAM had similar safety and tolerability. Moreover, in subjects given OLZ + SAM, less nausea was observed compared to SAM alone. Therefore, OLZ + SAM could offer effective treatment of schizophrenia with less weight gain and metabolic risk.