• INCLUSION CRITERIA:

Volunteers will qualify if they meet the following criteria:

1. Good general health. In general, subjects will be required to take no medications. However, individuals taking medications for obesity-related co-morbid conditions, who have not had changes in dosage for more than 6 months, may be included, at the discretion of the principal investigator.
2. Age 18-50 years.
3. Female sex. In this pilot study, we seek to decrease the variability of subject response to the greatest extent possible. Since women have a higher prevalence of obesity than men, and tend to be the group that most uses weight loss pharmacotherapy, we will only study women in the pilot investigation. Subsequent studies with include both sexes.
4. Regular menses (either spontaneous or as a result of oral contraceptive pills) or post-menopausal status (no menses for at least 3 months).
5. Obesity, defined as body mass index (BMI) between 30 and 40 kg/m(2) but weight under 300 lbs, in order for subject to be able to undergo DEXA scanning with the Hologic instrument available in the Nuclear Medicine Department.
6. A negative pregnancy test at the initial evaluation. Sexually active women must be using an effective form of birth control. These methods include abstinence, oral contraceptives, an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). (One of these methods must have been used by the subject for at least two months prior to the start of the study). If one of these cannot be used, contraceptive foam with a condom is recommended.

7. Willingness to participate in the research protocol.

   EXCLUSION CRITERIA:

   Volunteers will be excluded (and referred to non-experimental treatment programs as needed) for the following reasons:

   1. A presence of major illnesses: renal, hepatic (other than obesity-related steatosis), gastrointestinal, most endocrinologic (e.g., Cushing syndrome, hyper- or hypothyroidism, pheochromocytoma), hematological problems or pulmonary disorders; or porphyria;
   2. History of anaphylaxis, asthma, urticaria, rhinitis, allergic rash, or other allergic disease requiring antihistamine treatment; subjects with a history of antihistamine treatment for a self-limited allergic reaction such as to poison ivy or to a medication that they are no longer taking may be included at the discretion of the primary investigator.
   3. History of peptic ulcer disease;
   4. Baseline QT interval prolongation (greater than or equal to 480 msec QTc) because of reports of histaminergic compounds causing prolonged QT interval and cardiac arrhythmias in susceptible patients (i.e. those with prolonged QT interval at baseline);
   5. Current smokers of tobacco products;
   6. Self-reported lactose intolerance;
   7. Self-reported food allergy to foods used in standardized food array in this protocol or to betahistine itself;
   8. Subjects following a diet with specific food requirements such as vegetarian, vegan, or kosher because of the use of a standardized food array in this protocol;
   9. Subjects with a history of DSMIV classifiable eating disorders such as anorexia nervosa, bulimia nervosa, or binge-eating disorder will be excluded from the current proof-of-concept study;
   10. Women with reproductive potential who are pregnant or who are currently nursing an infant;
   11. Individuals who have current substance abuse or a psychiatric disorder or other condition that in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study;
   12. Subjects who regularly use prescription medications unrelated to the complications of obesity (especially vasoactive compounds such as calcium channel blockers, nitrates, beta-blockers, etc.), subjects using H2 blockers for dyspepsia, and subjects who require chronic use of antihistamines for allergic conditions; oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication for at least 3 months prior to study entry may be eligible. Allowable medications may include statins for the treatment of dyslipidemia and low-dose aspirin for primary prevention of acute coronary syndrome. Medications used for the treatment of hypertension will not be allowed because of the potential vasodilatory activity of betahistine.
   13. Recent (3 months) use of anorexiant medications;
   14. Weight change of more than 3% of body weight in the past two months;
   15. Subjects with a consistently (2 weeks apart) elevated systolic blood pressure of greater than 160 mm Hg and/or a diastolic blood pressure greater than 95 mm Hg.