Following an overnight abstinence from smoking, the participants arrived at the outpatient clinic at approximately 8 AM for the experimental session, which lasted about 3 hours. Abstinence from smoking was confirmed by measuring expired carbon monoxide (CO; <10 parts-per-million). The participants were instructed to continue their usual caffeine intake (to prevent caffeine withdrawal) and were asked to fast after midnight to minimize the nicotine-induced nausea that can be enhanced with food. Prior to the experimental sessions, a urine drug screen was conducted to rule out recent drug use and ensure that the inclusion criteria were met. An indwelling catheter was set in an antecubital vein, and the baseline measures were collected. The study used a single-blind design. Smokers received IV saline, followed by two increasing doses of IV nicotine, (0.5 and 1.0 mg/70 kg). An escalating dose schedule was selected to increase study safety. Subjects were first exposed to saline, followed by a low dose of nicotine, and finally a high dose of nicotine. This administration schedule was also used to avoid residual effects from the preceding nicotine dose to saline.
