Outcome measures assessed biochemical, physiological, subjective, and cognitive domains. Biochemical measures included CO, plasma nicotine, cotinine, and 3-hydroxycotinine (3HC). The plasma nicotine concentrations and expired CO were used to confirm the overnight abstinence from smoking. Plasma cotinine concentrations were used as a measure of prior nicotine exposure (28). Expired CO, plasma nicotine, 3HC, and cotinine measurements were taken before the experimental session. Physiological measures included blood pressure (systolic and diastolic) and heart rate. These measures were taken during the medication treatment and in the experimental sessions at −5, 1, 2, 3, 5, 8, 10, and 15 min intervals following the saline or nicotine deliveries. Plasma cortisol measurements were taken at baseline, before each of the three injections, and at the end of the session. Plasma cortisol has been shown to be sensitive to nicotine administration and abstinence from nicotine (29–32). Studies also suggest that the COMT Val158Met polymorphism may influence cortisol release in response to stress or drugs of abuse (33, 34).