Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

The acute effects of smoking a low or high nicotine cigarette on hypothalamic-pituitary-adrenal (HPA) hormones, subjective responses and cardiovascular measures were studied in 20 healthy men who met DSM-IV criteria for nicotine dependence. Within 4 puffs (or 2 min) after cigarette smoking began, plasma nicotine levels and heart rate increased significantly (P<0.01), and peak ratings of “high” and “rush” on a Visual Analogue Scale (VAS) were reported. Reports of “high”, “rush” and “liking” and reduction of “craving” were significantly greater after smoking a high nicotine cigarette than a low nicotine cigarette (P<0.05). Peak plasma nicotine levels after high nicotine cigarette smoking (23.9 ± 2.6 ng/ml) were significantly greater than after low nicotine cigarette smoking (3.63 ± 0.59 ng/ml) (P<0.001). After smoking a low nicotine cigarette, ACTH, cortisol, DHEA and epinephrine did not change significantly from baseline. After high nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88 ± 5.34 pmol/L within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001), DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA increased significantly within 20 min (P<0.05) and reached peak levels of 424 ± 48 nmol/L and 21.13 ± 2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones, subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking.