The purpose of the overall parent study is to determine the impact of gender and hormones (estradiol, progesterone, testosterone and cortisol) on responses to stress and smoking cues presented in daily, "real-world" cue presentations compared to a final cue session in a lab. In addition, in the portion of the study that incorporates clinical trials elements and is reported here, the study will examine the impact of a single dose of oxytocin (chemical produced in the body) versus placebo (inactive substance) on reactivity to a stress procedure (Trier Social Stress Task) in smokers.

The overall parent study involves a cue presentation technology known as "CREMA" (Cue Reactivity Ecologic Momentary Assessment) which delivers four daily cue presentations to you on a handheld device during your everyday routine. Additionally, the study involves daily collection of saliva samples for hormonal testing. These daily procedures will provide information about the role of cues and hormones in daily life. The clinical trial portion of the study (reported here) consists of measures collected within the laboratory.

Despite considerable advances in treatment development, cigarette smoking remains the leading cause of preventable death in the United States, and most smokers engaged in treatment are unsuccessful in quitting. The burden of illness is disproportionately borne by female smokers, who are less responsive to cessation interventions than males. The relationships between stress, craving, and smoking behavior are recognized as key factors underlying gender differences in nicotine dependence, but must be better understood and characterized to yield avenues for interventions addressing this critical health disparity.

In prior and ongoing SCOR studies, our research team has demonstrated gender and menstrual cycle/sex hormone influences on reactivity to laboratory-presented cues. Building from these laboratory findings, we propose taking two important next steps: (1) evaluating the experience of craving in the "real world" natural environment of female and male smokers, and (2) examining the impact of a safe and novel pharmacological intervention (oxytocin) on stress reactivity in female and male smokers.

If, as hypothesized, gender, sex hormones, and oxytocin administration influence the relationships between stress, craving, and smoking behavior, the findings could substantially address a key gender-related health disparity. Such knowledge could also inform the development of gender-specific interventions to enhance female smokers' response to cessation treatments. Therefore, the knowledge to be gained from the proposed study may yield significant public health benefits.

Inclusion Criteria:

1. Females and males age 18 - 45 who smoke at least an average of 5 cigarettes per day for at least past 6 months
2. Females must be post menarche and pre-menopausal, have a regular menstrual cycle between 25 and 35 days, and, if recently pregnant, be at least three months post-delivery/breast feeding
3. Participants must submit a carbon monoxide sample of ≥ 5 ppm at their screening visit

Exclusion Criteria:

1. Any serious or unstable medical or psychiatric disorder that may, in the judgment of the study physician, interfere with study completion
2. Participants must not meet criteria for PTSD
3. Any medication (e.g., propranolol) that may interfere with psychophysiological (e.g., heart rate) monitoring
4. Current substance dependence other than nicotine and caffeine use, in the past month
5. Use of other tobacco products
6. Females must not be pregnant, breast feeding, status post hysterectomy or bilateral oophorectomy, or taking birth control or hormone replacement medication that would affect the menstrual cycle
7. Males must not be status post orchiectomy

During laboratory visit after oxytocin or placebo administration (up to 3 hours after medication administration; any unresolved AEs at the end of the laboratory session are followed post-session to conclusion/resolution).