This will be a double-blind, placebo-controlled study that tests the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal severity and smoking behavior. Once the intake and physical examination is completed and eligibility is determined, subjects will participate in a baseline session to become familiar with the study procedures and to assess baseline measures of withdrawal, smoking urges, pain sensitivity, and cognitive performance. Subjects will be asked to refrain from consuming alcoholic beverages and drugs during their study participation. This will be verified by urine drug screening and breathalyzer before the session and during outpatient visits. If results indicate non-compliance with these study procedures, subjects will be discharged from the study.~Participants will be assessed for compliance with medication treatment, withdrawal severity, recent smoking behavior, and cognitive function during treatment visits on Days 1 and 4. On Day 7, following overnight abstinence from smoking, participants will attend a test session that models relapse to smoking. During this session, subjects will have the option to smoke, or to delay smoking in exchange for monetary compensation (45). To examine if mifepristone's proposed therapeutic effects last beyond the treatment duration (as observed in previous studies), there will be 1-week and 1-month follow-up assessments on smoking behavior, urges to smoke, endocrine biomarkers, and cognitive function.~Participants in each group will complete the laboratory-based, delayed smoking procedure in a designated, negative pressure room in Bldg. 36 of the West Haven VA just after assessing pain sensitivity with the cPT. This sequence allows the cPT to assess pain sensitivity, a potential biomarker of relapse behavior, and to also be used as a mild stressor prior to participation in the smoking relapse model. Participants will be instructed to abstain from smoking after 10 pm the night before Test Sessions. Abstinence will be confirmed the morning of the session by measuring a breath CO level of < 8 ppm.
The purpose of this protocol is to examine whether mifepristone, a medication with glucocorticoid receptor antagonist activity, may be a potential treatment for Tobacco Use Disorder (TUD). Mifepristone has already shown promise as a potential treatment for PTSD (1) and alcohol use disorder (AUD) (2), but no previous studies have examined the therapeutic potential of mifepristone for TUD. This will be a double-blind, placebo-controlled study on the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal severity, and smoking behavior.