Weight Loss Study: Genetics and Response to Naltrexone/Bupropion

Inclusion Criteria: * Men and women ages 18-65 years * BMI 30-50 kg/m2 or * BMI 27-29.99 kg/m2 with at least one weight-related comorbidity including controlled hypertension, dyslipidemia, obstructive sleep apnea, or osteoarthritis of a weight-bearing joint. Exclusion Criteria: * Obesity of known endocrine or hypothalamic origin * HbA1c \> 6.5% * Cerebrovascular, cardiovascular, hepatic or renal disease * History of seizures, serious psychiatric illness or suicide attempts, drug or alcohol misuse within prior 24 months * Glaucoma * Current tobacco use on a regular basis * Use of dopamine agonists, opioid analgesics, antipsychotics, antidepressants, neuroleptics, naltrexone, diabetes medications * Use of Monoamine oxidase (MAO) inhibitors \< 14 days prior to screening * Concomitant use of CYP2B6 inhibitors * History of anorexia nervosa or bulimia * Previous surgery for obesity * Weight loss device intervention within prior 2 years * Currently pregnant or lactating, planning pregnancy or refusal to use birth control when appropriate (Women of childbearing potential will be required to use effective contraception.) * Blood pressure \> 145/95 (use of anti-hypertensives will be allowed with the exception of verapamil, which can cause hyperprolactinemia) * Clinically significant thyroid disease * Triglycerides \> 499 mg/dl * Current use or use of weight loss medication within prior six months * Any lifetime weight change deemed significant by Principal Investigator * An affirmative answer to any question in the Columbia-Suicide Severity Rating Scale