Effects of low- and high-nicotine cigarette smoking on mood states and the HPA axis in men

Abstract

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 American Psychiatric Association Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within four 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 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, adrenocorticotropin hormone (ACTH), cortisol, dehydroepiandrosterone (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 and 21.13+/-2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking.

Figure 1

: Plasma Nicotine Levels After Smoking a Low or High Nicotine Cigarette. Plasma nicotine levels after smoking a high nicotine cigarette (filled circles) and a low nicotine cigarette (open circles) are shown on the left ordinates. Time (min) is shown on the abscissae. Points above BL were collected 10 min before cigarette smoking began at time 0. The 12 min cigarette smoking period is indicated by a grey rectangle. Each data point is the average (± S.E.M.) of 10 subjects. Statistical analyses indicated significant changes in plasma nicotine levels from baseline in both low [df=18, F=6.96, P=.03)], and high [df=18, F=21.8, P<.0001] nicotine cigarette groups. Significant changes from the pre-smoking baseline are indicated by asterisks (* = P < 0.05; ** = P < 0.01). Daggers indicate points at which plasma nicotine levels after smoking a low nicotine cigarette differed from plasma nicotine levels after smoking a high nicotine cigarette († = P < 0.05; †† = P <0.01) [df=1, F= 23.9, P=.0004].

Figure 2

: ACTH, Cortisol, DHEA and Epinephrine Levels after Smoking a Low or High Nicotine Cigarette. Hormone levels after smoking a high nicotine cigarette (filled circles) and a low nicotine cigarette (open circles) are shown on the left ordinates. Time (min) is shown on the abscissae. Points above BL were collected 10 min before cigarette smoking began at time 0. The 12-min cigarette-smoking period is indicated by a grey rectangle. Each data point is the average (± S.E.M.) of 10 subjects. Statistical analyses indicated significant changes from baseline in ACTH levels [df=18, F= 8.8, P=.005], epinephrine levels [df=18, F=3.9, P=.05], DHEA levels [df=18, F=8.7, P=.0006], and cortisol levels [df=18, F=9.0, P=.002] after high dose nicotine. ACTH (pmol/L) and epinephrine (pg/ml) are shown in the left column; cortisol (nmol/L) and DHEA (ng/ml) are shown in the right column. Asterisks indicate points that were significantly different from baseline (* = P< 0.05; ** = P< 0.01). Daggers indicate points at which hormone levels were significantly different after high nicotine cigarette smoking than after low nicotine cigarette smoking († = P< 0.05; †† = P< 0.01); ACTH [df=1, F=7.0, P=.016], Epinephrine [df=1, F=5.8, P=.026], DHEA [df=1, F=4.8, P=.048], and cortisol [df=1, F=5.5, P=.03].

Figure 3

: Cardiovascular Measures after Smoking a Low or High Nicotine Cigarette. Heart rate (bpm), systolic and diastolic blood pressure (mm/Hg) after smoking a high nicotine cigarette (filled circles) and a low nicotine cigarette (open circles) are shown on the left ordinates in the first, second and third rows, respectively. Time (min) is shown on the abscissae. Points above BL were collected 10 min before smoking began at time 0. The 12-min cigarette-smoking period is indicated by a grey rectangle. Each data point is the average (± S.E.M.) of 10 subjects. Statistical analyses indicated significant changes from baseline in heart rate [df=18, F= 18, P<.0001], systolic blood pressure [df=11, F=6.1, P=.001], and diastolic blood pressure [df=11, F=7.0, P=.0006] after high nicotine cigarettes. Asterisks indicate points that were significantly different from baseline (* = P< 0.05; ** = P< 0.01). Daggers indicate points that were significantly different after high nicotine cigarette smoking than after low nicotine cigarette smoking († = P< 0.05; †† = P< 0.01); Heart Rate [df=1, F=6.3, P=.021], Systolic Blood Pressure [df=1, F=5.9, P=.026], and Diastolic Pressure [df=1, F=5.8, P=.03].

Figure 4

: Reports of Subjective Effects After Smoking a Low or High Nicotine Cigarette. Subjective ratings on a Visual Analogue Scale (VAS) (0-100) are shown on the left ordinates and time (min) is shown on the abscissae. Points above BL were collected 10 min before smoking began at time 0. Each data point is the average (± S.E.M.) of 10 subjects. The 12 min cigarette smoking period is indicated by a grey rectangle. Asterisks indicate points that were significantly different from baseline (* = P< 0.05; ** = P< 0.01). Statistical analyses indicated significant changes from baseline in reports of “high” after high nicotine cigarettes [df=18, F=16.9, P<.0001] and low nicotine cigarettes [df=18, F=5.2, P=.01; reports of “liking” after high nicotine cigarettes [df=18, F=14.1, P<.0001] and low nicotine cigarettes [df=18, F=3.9, P=.05]; reports of “rush” after high nicotine cigarettes [df=18, F=13.2, P<.0001] and low nicotine cigarettes [df=18, F=5.1, P=.009; and reports of “craving“ after high nicotine cigarettes [df=18, F=8.1, P=.0007] and after low nicotine cigarettes [df=18, F=5.6, P=.007]. Daggers indicate points that were significantly different after high nicotine cigarette smoking than after low nicotine cigarette smoking († = P< 0.05; †† = P<0.01) “high “ [df=1, F=4.5 P=.049], “like”[df=1, F=6.2, P=.023], “rush” [df=1, F=6.3, P=.02], and “craving” [df=1, F=5.6, P=.04].