Pexacerfont

Background:
- Stress can cause people to give in to temptations to eat less healthily. People who are on weight loss diets often have problems sticking to their diets when they are stressed. Some tests have shown that the drug pexacerfont can help reduce stress-related seeking of high-calorie foods. However, it has not been tested on reducing food craving. Researchers want to test pexacerfont on people who are on diets to see if it can reduce stress-related food cravings.
Objectives:
- To see if pexacerfont can help reduce stress-induced food cravings.
Eligibility:
- Individuals between 21 and 65 years of age who are on a diet to control their weight.
Design:
Participants will be screened with a physical exam and medical history. This study requires seven visits over about 35 days.
Participants will take either pexacerfont or placebo pills during the study. They will have three pills every morning. They will record video of themselves taking the pills every day.
Every evening, participants will fill out a questionnaire. It will ask questions about feelings and behaviors related to eating and food craving.
Participants will have regular study visits while taking the pills. The visits will involve questions about stressful situations and food cravings. One visit will involve a mildly stressful math test, followed by tasting of different foods. This test will look at whether pexacerfont can affect food preferences. Participants will provide blood and saliva samples as directed at these study visits.
Participants will have follow-up phone calls 1, 3, and 6 months after the end of the study.

Background:
- Individuals who are dependent on alcohol often have feelings of anxiety, irritability, anger, and depression. These feelings, as well as stress, may contribute to the risk of relapse and continued drinking. Studies have shown that alcohol consumption increases the activity of certain molecules in the brain known as CRH1 receptors, which are key to producing the body s response to stress, and whose activation generates feelings of anxiety. Researchers are interested in learning whether the experimental drug pexacerfont, which blocks CRH1 receptors and has been studied in individuals with anxiety disorders and depression, can lessen anxiety and craving for alcohol as part of alcohol-dependence treatment.
Objectives:
- To determine the safety and effectiveness of pexacerfont as a treatment for anxiety-related alcohol craving.
Eligibility:
- Individuals between 21 and 65 years of age who are alcohol-dependent and have problems with anxiety.
Design:
This study requires an inpatient admission to the NIH Clinical Center for approximately 1 month, with two additional study visits 1 week and 1 month after discharge from the hospital.
Participants will be screened with a medical history, physical examination, and blood and urine tests.
During the inpatient period, participants will have standard treatment for alcohol dependence, including support and interventions from institute staff to address cravings, anxiety, or other psychological problems. Participants will not receive formal psychological treatment or psychiatric medications for anxiety, but will receive training in relaxation techniques.
Participants will be assigned to take either pexacerfont or placebo for 3 weeks. During this time, participants will have the following procedures:
Frequent blood tests.
Rating scales and questionnaires about alcohol cravings and anxiety.
Dexamethasone suppression test with frequent blood draws to study hormone response to stress.
Social stress test involving public speaking, followed by blood samples and questionnaires on alcohol craving.
Cue Reactivity (CR) session to study cravings and responses to alcohol-based cues.
Functional magnetic resonance imaging scan to evaluate brain activity while taking the medication or placebo.
Participants will have two follow-up visits for additional blood tests and questionnaires about the effects of the treatment ^.