Disclosed are compositions for affecting weight loss comprising a firstcompound and a second compound, where the first compound is an opioidantagonist and the second compound causes increased agonism of a melanocortin3 receptor (MC3-R) or a melanocortin 4 receptor (MC4-R) compared to normalphysiological conditions. Also disclosed are methods of affecting weight loss,increasing energy expenditure, increasing satiety in an individual, orsuppressing the appetite of an individual, comprising identifying anindividual in need thereof and treating that individual to antagonize opioidreceptor activity and to enhance .alpha.-MSH activity.
