Baseline Minnesota Nicotine Withdrawal Scale (MNWS)37 and Brief Questionnaire of Smoking Urges (BQSU) 38 were completed after IV lines were established. After baseline assessments, subjects were administered IV doses of saline, followed in uniform order by escalating doses of nicotine (0.5 mg per 70 kg of body weight and 1 mg per 70 kg of body weight). Each infusion lasted 30 seconds and was separated from the preceding one by 30 minutes. The first dose of nicotine, 0.5 mg per 70 kg of body weight, is approximately equal to the dose of nicotine delivered by smoking one-half of a cigarette, while the second dose of nicotine, 1.0 mg per 70 kg of body weight, is approximately equal to the dose of nicotine delivered by smoking 1 cigarette.39 Subjects repeated the MNWS and BQSU 20 minutes after the final infusion of nicotine. One hundred seventy-nine subjects completed the MNWS and 177 subjects completed the BQSU. The distribution of MNWS and BQSU outcomes is shown in Fig S2. DSM-IV nicotine withdrawal was not measured in the laboratory subjects. All laboratory study subjects provided written informed consent prior to participation, and were paid for their participation. Yale University and the VA Connecticut Healthcare
