A Study Using Functional Magnetic Resonance Imaging (fMRI) to Assess the Effects of Naltrexone SR/ Bupropion SR Therapy in Overweight or Obese Subjects

Inclusion Criteria: * Right-handed, female subjects, 18 to 45 years of age * Body mass index (BMI) ≥ 27 and ≤ 40 kg/m² * Free from clinically significant illness or disease as determined by medical history and physical examination * Able to provide proof of identity during the enrollment process * In good general health, without clinically significant medical history, physical examination findings or laboratory results * Laboratory values obtained within 30 days of study entry within normal range for healthy volunteers. * Normal urinalysis on initial screening day defined as: negative glucose, negative or trace protein, and negative or trace hemoglobin * Normotensive (systolic ≤140 mm Hg, diastolic ≤90 mm hg) * On no concomitant medications with the exception of oral contraceptives, vitamins, and over the counter pain, indigestion or allergy medication * All women of child bearing potential must be non-lactating, must have a negative STAT pregnancy test, and agree to use effective contraception methods throughout study period and for 30 days after discontinuation of study drug. The following are considered effective methods of contraception: Combination or progestin-only birth control pills (oral contraceptives), vaginal contraceptive rings, contraceptive patches, Depo Provera, intrauterine devices, barrier methods with spermicide (condom/foam, diaphragm/ spermicide), abstinence. (Subjects who have had a tubal ligation, hysterectomy or are post-menopausal for 2 years are considered NOT to be of child bearing potential) * For women not using hormonal methods of contraception, should be in the follicular phase of the menstrual cycle at the baseline visit. * Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to baseline. On screening and study days, we will test the subjects' urine for presence of nicotinine/cotinine (STAT) test as confirmatory evidence of being a non-smoker in addition to their self-report. A Tobacco Questionnaire and Breath CO will also be administered for eligibility on the day of screening for confirmation purposes. * No clinically significant abnormality on ECG, baseline QTc \<470 * Able to comply with all required study procedures * Available for follow up for the duration of the study * Willing and able to give written informed consent Exclusion Criteria: * Obesity of known endocrine or genetic origin (e.g., untreated hypothyroidism, Cushing's syndrome, Prader Willi Syndrome, established Polycystic Ovary Syndrome) * Inability to participate in fMRI scanning sessions * History of occupational exposure to metal flakes in their bodies or eyes. * History of known indwelling ferromagnetic metals or fragments. * History of acute or chronic illness that requires medical therapy including active gastrointestinal conditions that might interfere with drug absorption * History or presence of hepatic, renal, cardiovascular or gastrointestinal diseases * Type I or Type II diabetes mellitus requiring pharmacotherapy * Active malignancy or history of malignancy (other than non-melanoma skin cancer or surgically cured cervical cancer) within 5 years of enrollment * Serious psychiatric illness, including lifetime history of psychiatric hospitalization, suicide attempt, bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa; current serious personality disorder, (e.g. borderline or antisocial), major depressive disorder within the previous two years, suicidal ideation or need for psychiatric treatment in the previous 6 months. * In need of medications for the treatment of a psychiatric disorder within the previous 6 months prior to randomization. * IDS-SR total score \>25 or scores \>1 in items 5 (sadness), 6 (irritability), 7 (anxiety/tension) or 18 (suicidality) * History of alcohol or drug abuse, current or within 2 years * Unable to abstain from caffeinated product consumption for at least 48 hours * History of surgical intervention for obesity * Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization. * History of hypersensitivity to bupropion or naltrexone * History of seizure disorder or predisposition to seizures (e.g., history of cerebrovascular accident, brain surgery, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥ 15 minutes, skull fracture, subdural hematoma, or febrile seizures) or need for therapy with anticonvulsant medication. * History of treatment with bupropion or naltrexone within 12 months * Positive urine drug screen - STAT test performed on each day of study. * Pregnant or breast-feeding * Planned surgical procedure or trip that can impact the conduct of the study * Use of investigational drug, device or procedure within 30 days * Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study * Participation in any previous clinical trial sponsored by Orexigen Therapeutics. * Study personnel, sponsor representatives and their immediate families.