Part I will be a 2-week evaluation phase. In Part I, subjects undergo a diagnostic interview for symptoms and treatment along with medical, side effect measures, and neuropsychological tests (tests for memory, attention, and motor task skills). An electrocardiogram (EKG), a urine sample, and about 3 tablespoons of blood will be taken for laboratory tests. Women will have a pregnancy test. This part of the study is 3-4 visits. The time of the visits will be about 8 hours.

Part II is a 16-week treatment phase subjects will be randomly assigned to either rimonabant or placebo for a 16-week period. The medication will be given in unmarked capsules so that subjects will not know which medication they are receiving. Only the pharmacist will know which medications subjects are receiving. If an emergency occurs we will break the blind and give appropriate care. This phase will require one visit every week and each visit may take up to 2-3 hours. Subjects will be examined every week to check symptoms side effects. Subjects symptoms will be evaluated using specially designed rating scales, to ask about their daily experiences and feelings. Evaluations that occur every 4 weeks may take about 2 hours. At week 8 and week 16 laboratory tests will be repeated. These tests will be compared to the baseline tests taken in Part I. The end of study tests may take up to a total of 8 hours and may require 3-4 visits. All testing is done for research purposes only and would not be performed if subjects were not participating in this study. The total number of visits requested for this study will be 16-20. When subjects undergo neuropsychological testing, we will examine their ability to learn and remember numbers and words to pay attention and to quickly perform motor tasks. A motor task is when you use your hands to perform a task such as placing pegs into a piece of wood. These tests will take about 2 hours and are done at the beginning of Part I and the end of Part II.

Diet and exercise counseling will be held weekly for groups and individuals. Sessions will focus on topics such as calories, fat content, portion control and determining a healthy weight. We will request that participants maintain a food diary and exercise approximately 30 minutes/3 times per week. Subjects will be encouraged to attend the counseling sessions. Transportation will be available for subjects. If patients have not attended sessions, they will be reeducated on the importance of attending sessions at the time of clinical ratings.Subjects will not be discharged from the study if they do not attend sessions.

Randomization will be done using a permuted block randomization system, and will be stratified by clozapine/olanzapine treatment at baseline. Treatment assignment order is random within each block, and the total number of patients assigned to each treatment is equal. The block sizes will vary between sizes 2 and 4 in random sequence. The unblinded pharmacist will be notified of the treatment assignment, and will inform unblinded pharmacists at the other sites about which study medication to dispense. In an emergency, research staff will be able to contact the pharmacy for unblinding. Rimonabant will be available in 20 mg capsules with matched placebo.

For outpatients study medication will be dispensed on a weekly basis plus two extra days of medication. Inpatient subjects will receive their study medication daily from the Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP) central pharmacy by a non-blind pharmacist. The blind will be broken only if a medical emergency requires this information. If this occurs, the patient will be withdrawn from the study.

All raters, investigators and other staff will be blind to treatment assignment except for the pharmacist. The pharmacist does not participate in assessing any of the primary symptom or side effect dependent variables and conveys no information about treatment assignment to patients or staff except in a medical emergency.

Patients receiving 75% of their assigned medication will be considered compliant. Outpatient compliance will be monitored through weekly pill counts and subject interviews. Inpatient compliance will be monitored through inpatient medication records. If a patient is observed to be non-compliant then this will be discussed with the patient and a plan formulated to bring the patient back within the compliance parameter. For outpatients the plan may include contacting the patients caretaker or scheduling increased clinic visits. These monitoring procedures have been used in other MPRC studies and have resulted in high levels of compliance. Compliance patterns will be carefully monitored in each treatment group and will be described as part of any presentation of study results.

Satiety is defined as the reduced willingness to eat after a meal, not due to sickness or other extraneous factors and can be thought of as sensations of fullness. A preload and a test meal will be used in this study. The preload is a fixed amount of food given to the participant that is consumed in its entirety. The test meal is a food or foods served, following the preload, in sufficient quantity so that the participant can eat as much as desired. The amount consumed of the test meal is measured and used as an index of satiety. Likert and Visual Analog Scales (VAS) will also be used.

We will employ both the preload-test meal paradigm along with rating scales in the present study to investigate the effects of rimonabant on satiety signaling. The testing will occur at baseline, week 8, and week 16 to see if the effect changes. All three testing occasions will be the same. Participants will arrive after skipping breakfast and given a preload of 12 oz. of Ensure (375 kcal) served chilled in a large, plastic cup. Hunger ratings will be taken at baseline, then every 30 minutes for 90 minutes. After 60 minutes a test meal consisting of a pre-weighed bowl each of Reduced Fat Wheat Thins and Nilla Wafers will be given. These will be kept in separate bowls so that exact caloric consumption can be measured. The test meal will be served with 12 oz. of water served chilled in a large plastic cup. Satiety will be assessed by the quantity of Wheat Thins, Nilla Wafers, and water consumed and the difference between the hunger rating score from baseline for each time point.

About 75% of subjects will be smokers. Smoking measures will be performed on those with \>8 ppm CO in expired breath and who smoke at least 5 cigarettes daily. One approach to studying tobacco craving in the laboratory is to compare smokers responses when exposed to neutral and smoking-related in vivo cues. In vivo or "real-life" cues are either presented by the experimenter or involve manipulation of materials by the participant. For this study, after smoking a cigarette at baseline (15 minutes before testing begins), patients will be asked to complete the Tobacco Craving Questionnaire (TCQ) and the Positive and Negative Affect Schedule (PANAS). Participants will then be exposed to two experimental trials presented in random order: 1) smoking cues, and 2) neutral cues.Each trial will last 20 minutes. Participants will complete the TCQ and PANAS immediately and 10 and 20 minutes after cue exposure. There will be a rest period between trials. During the rest period, the patient will complete other study assessments lasting 30-60 minutes. After the assessments, the patient will smoke again and then will complete the ratings and cue reactivity session for the second random condition at the same time points (baseline, immediately after, 10 and 20 minutes).Trials will begin with the experimenter placing a tray containing an opaque cover on a table in front of the participant. In the smoking cue condition, a pack of the participants preferred brand of cigarettes a lighter and an ashtray will be under the tray cover. In the neutral cue condition, a pack of unsharpened pencils and a pencil sharpener will be under the cover. When instructed, the participant will lift the cover on the tray. In the smoking cue condition, participants will take one cigarette out of the pack light it without puffing hold it and look at it. At the end of the exposure period participants will extinguish the cigarette, and replace the cover on the tray. In the neutral cue condition, participants will take one pencil out of the pack sharpen it hold it and look at it.

The Iowa Gambling Task (IGT) is a computer-administered cognitive test that measures risk-reward decision-making. Performance is impaired in patients with brain lesions in the ventromedial prefrontal cortex and in people who abuse alcohol, cocaine, marijuana, methamphetamine, opiates, or multiple illegal drugs. Patients with schizophrenia show normal IGT performance in some studies. In particular, adolescent patients and adults with catatonic schizophrenia show impairment. One study found that IGT performance was significantly correlated with negative symptoms. In this study, subjects will take one of two equivalent versions of the IGT at study entry and study completion. Each task session will take up to 30 minutes.

The Tobacco Craving Questionnaire (TCQ) is a questionnaire designed to assess current tobacco craving. Factor analysis of the 47-item TCQ resulted in four factors: 1) emotionality, smoking in anticipation of relief from withdrawal or negative mood; 2) expectancy, anticipation of positive outcomes from smoking; 3) compulsivity, an inability to control tobacco use; and 4) purposefulness, intention and planning to smoke for positive outcomes. We will use a 12-item version of the TCQ, comprising the three items from each factor that exhibited optimal within-factor reliability (Cronbachs coefficient alpha) and inter-item correlation. The 12-item TCQ is as valid and reliable as the 47-item version. TCQ items are rated on a scale from 1 strongly disagree to 7 strongly agre. Factor scale scores for each participant are obtained by summing the three items.

The PANAS is a 20-item scale in which 10 items describe positive mood (enthusiastic, interested, determined, excited, inspired, alert, active, strong, proud, attentive) and 10 items describe negative mood (scared, afraid, upset, distressed, jittery, nervous, ashamed, guilty, irritable, hostile). Each item is rated on a 5-point scale (not at all, a little, moderately, quite a bit, extremely). The PANAS shows high internal consistency and test-retest reliability. Subjects can leave the study at any point. If a participant experiences worsening of psychotic symptoms (relative to the baseline BPRS, an increase of 3 points or more OR an increase from a 5 to 7 on any one of the following BPRS items: somatic concern, conceptual disorganization, hostility, suspiciousness, hallucinatory behavior, or unusual thought content OR an increase of 2 or more on the CGI global severity OR the subject is judged to be entering an exacerbation of his/her illness by the treating clinician), the patient will be discontinued from the study. Other reasons for study termination include evidence of suicidal thinking or behavior, or the development of or worsening of significant depressive symptoms (score at any point in the study of \>10 on the CDS or a 3 on the suicidal item), complete cessation of eating and drinking for \> 24 hours, pregnancy, or blood pressure \> 165/95 on three consecutive readings. Once a participant is discontinued from the study for whatever reason, completion ratings will be performed. This includes laboratory tests rating scales and neurocognitive assessments.

If a patient is prematurely terminated from the study, they will resume their standard treatment. At the end of the study patients will not have the option of continuing rimonabant because it is not FDA approved in the US. Other interventions to improve weight and metabolic profiles will be discussed with the patients.