Pexacerfont for Reduction of Stress-induced Tobacco Craving, Nicotine Reinforcement, and Brain Activation in Humans

Background:

• Stressful situations often cause tobacco cravings. These cravings can make it very difficult for smokers who are trying to quit. Research has shown that craving may involve hormone pathways in the brain. The anti-anxiety drug pexacerfont acts on these hormone pathways. Researchers want to see if pexacerfont can act on the brain and lessen stress-related tobacco cravings in smokers who are trying to quit.

Objectives:

• To test the effects of pexacerfont on tobacco craving in smokers who want to quit smoking.

Eligibility:

• Smokers between 18 to 55 years of age who are trying to quit. (Participants must have smoked at least 10 cigarettes per day for at least 1 year.)

Design:

• Participants will be screened with a physical exam and medical history.
• Participants will be assigned to take either pexacerfont or a placebo. They will take three pills every morning for the first 7 days, then one pill every morning for 23 days.
• At the first visit, participants will provide blood and urine samples. They will then be asked to prepare a 5-minute speech and give it to the study researchers. They will also be asked to do mental math problems for another 5 minutes. During these tests, blood pressure, heart rate, sweating, and skin temperature will be measured. Participants will fill out questionnaires about stress levels, tobacco cravings, and personal experiences.
• Participants will take the study pills for 30 days. Before the 2-week point, participants will be asked to try to quit smoking for 2 weeks.
• Participants will have four study visits. These visits will involve brain imaging scans and emotional stress tests. Tobacco cravings and other stress levels will be measured at each study. Blood and urine samples may be collected at these studies.
• Participants will have follow-up visits and phone calls for up to 6 months after the end of the study visits.