The Effects of the Cannabinoid-1 Receptor Antagonist Rimonabant on Weight...

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DESCRIPTION (provided by applicant): This project will examine the efficacy and safety of a new medication, rimonabant, a cannabinoid CB1 receptor antagonist, in decreasing weight and improving metabolic parameters and cardiovascular disease risk in people with schizophrenia receiving second-generation antipsychotics. Additionally, the study aims to test the effects on adjunct rimonabant on patient perceived health outcomes, quality of life, smoking frequency and neurocognitive functioning. This 16 week randomized double-blind placebo controlled pilot study will enroll 60 subjects who have a BMI >30 or a BMI>27 with defined risk factors for cardiovascular disease. Subject enrollment should be completed within 24 months of this award. Results from this study will then be used to design further work with this drug, and other similar agents that may become available. There is a fourfold greater risk for metabolic syndrome in people with schizophrenia than in the general population and weight related morbidity and mortality in schizophrenia is considered a significant worldwide health burden. People with schizophrenia are also known to have increased mortality rates and the relative risk of having cardiovascular disease is almost 5 times higher than the general population. This rate is believed to be rising due to the use of new antipsychotic medications. These new medications have significant benefits, but cause the side effects of weight gain and metabolic abnormalities, including type II diabetes mellitus and hyperlipidemias. Rimonabant is a new medication that has been shown to significantly decrease weight and metabolic parameters, such as triglycerides, fasting glucose, insulin sensitivity and cholesterol in people who are overweight. If found safe and effective in the schizophrenia population, a group of people who are unlikely to adhere or benefit from exercise and dietary modifications, a new treatment method would be demonstrated that could markedly improve the overall health in this group and allow more effective use of antipsychotic medications. The results of this study will influence additional work in this area. With a strong development pipeline of antiobesity medications similar to rimonabant, there is no question whether rimonabant and other cannabinoid receptor antagonizing agents will be used in the seriously mentally ill. There should be direct evidence of efficacy and safety in these patients in order to provide truly effective treatments and further understanding of these disorders.