Obesity – metabolic complications

There is growing evidence for an important role of peripherally located CB1 receptors in metabolic regulation, which has gained further support by the pharmacological profile of novel, peripherally restricted CB1 antagonists. Compounds with limited brain penetrance retain efficacy in improving the hormonal/metabolic complications of obesity, but are devoid of behavioural effects that result from blocking CB1 receptors in the brain. Among peripherally restricted compounds, CB1 inverse agonists may offer distinct advantages over neutral antagonists, particularly as far as weight reduction and insulin sensitization are concerned. The improved therapeutic profile of such compound, due to the greatly reduced risk of neuropsychiatric side effects, warrants their clinical testing for the treatment of obesity and its metabolic complications, including fatty liver disease, insulin resistance and dyslipidemias.