Leptin, ghrelin, and endocannabinoids: potential therapeutic targets in anorexia nervosa.
Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been of short duration and included a limited number of subjects, often heterogenic with regard to stage and acute nutritive status. Thus, novel approaches are urgently needed. Body weight homeostasis is tightly regulated throughout life. With the discovery of orexigenic and anorectic signals, an array of new molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN.
Cancer cachexia and cannabinoids.
Anorexia and cachexia are diagnosed in more than two-thirds of all cancer patients with advanced disease, and are independent risk factors for morbidity and mortality. Anorexia, nausea and vomiting often are described as more significant inhibiting factors for quality of life of cancer patients than even intense pain. In 1986, delta-9-tetrahydrocannabinol (THC), the main effective constituent of cannabis, was licensed as an anti-emetic drug in cancer patients receiving chemotherapy. In addition, in clinical studies THC has shown significant stimulation of appetite and increase of body weight in HIV-positive and cancer patients. The appetite-stimulating effect of cannabis itself has also been well documented in many anecdotal cases.
The role of the endocannabinoid system in eating disorders: neurochemical and behavioural preclinical evidence.
The endocannabinoid system has long been known as a modulator of several physiological functions, among which the homeostatic and hedonic aspects of eating. CB1 receptors are widely expressed in brain regions that control food intake, reward and energy balance. Animal and human studies indicate that CB1 receptor agonists possess orexigenic effects enhancing appetite and increasing the rewarding value of food. Conversely, CB1 antagonists have been shown to inhibit the intake of food. Eating disorders include a range of chronic and disabling related pathological illnesses that are characterized by aberrant patterns of feeding behaviour and weight regulation, and by abnormal attitudes and perceptions toward body shape image. The psychological and biological factors underlying eating disorders are complex and not yet completely understood.
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