Additional Study Information: This 2-phase study aims to explore ways to predict who will respond well to the FDA approved weight loss drug lorcaserin and to understand the mechanisms that develop which limit drug efficacy. Subjects will be recruited for a 5-week crossover study (phase 1) with lorcaserin and placebo followed by treatment with lorcaserin for 24 weeks (phase 2). Phase 1 is five weeks long. Participants will be randomized to receive either lorcaserin or placebo for 7 days followed by a 3 week washout period. Participants will then be crossed over to receive 7 days of whichever treatment they did not receive the first time. Each subject will be studied twice: after receiving placebo and after receiving lorcaserin. During this phase of the trial we ask that participants remain weight stable and not try to lose weight. Each week of medication includes taking a pill (lorcaserin or placebo) twice a day. At the end of each week, participants will come to the clinic after a night of fasting. A lumbar puncture (spinal tap) will be performed and blood samples will be obtained. Subjects will then be fed a standardized breakfast (300 kcal). A laboratory test meal lunch will be given 4-hours later. Between breakfast and lunch participants complete a series of questionnaires and computer games. Phase 2, the weight loss phase of the study, six months long. Subjects will receive nutritional counseling to reduce their daily caloric intake to 600 kcal below their calculated caloric requirement and will be encourage to exercise moderately for 30 min daily. Subjects will visit the clinic once monthly during this study period for monitoring of vital signs and food counseling. Salivary cortisol levels will be obtained the night before the monthly visits. Blood will be obtained at months 1, 2, 4 and 6 for safety monitoring and protein and hormone level analysis. The final visit will include a fasting lumbar puncture, blood draw, breakfast meal, questionnaires and computer games, and a test meal lunch.