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 (Po0.01), 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 (Po0.05). Peak plasma nicotine levels after high-nicotine cigarette smoking (23.972.6 ng/ml) were significantly greater than after lownicotine cigarette smoking (3.6370.59 ng/ml) (Po0.001). 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 21.8875.34 pmol/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r ¼ 0.85; Po0.0001), DHEA (r ¼ 0.66; P ¼ 0.002), and epinephrine (r ¼ 0.86; Po0.0001). Cortisol and DHEA increased significantly within 20 min (Po0.05) and reached peak levels of 424748 and 21.1372.55 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.

Cocaine and nicotine have a number of similar behavioral and neurobiological effects. This study compared the acute effects of cocaine and cigarette smoking on luteinizing hormone (LH), testosterone (T), and prolactin. Twenty-four men who met American Psychiatric Association Diagnostic and Statistical Manual criteria for cocaine abuse or nicotine dependence were given intravenous cocaine (0.4 mg/kg) or placebo-cocaine, or smoked a low or high nicotine cigarette under controlled conditions. Placebo-cocaine or low nicotine cigarette smoking did not change LH, T, or prolactin. Peak plasma levels of 254 Ϯ 18 ng cocaine/ml and 22.6 Ϯ 3.4 ng nicotine/ml were measured at 8 and 14 min, respectively. LH increased significantly after both i.v. cocaine and high nicotine cigarette smoking (P Ͻ 0.01). These LH increases were significantly correlated with increases in cocaine and nicotine plasma levels (P Ͻ 0.001-0.003), and high nicotine cigarette smoking stimulated significantly greater increases in LH release than i.v. cocaine (P Ͻ 0.05). Testosterone levels did not change significantly after either cocaine or after high nicotine cigarette smoking. After i.v. cocaine, prolactin decreased significantly and remained below baseline levels throughout the sampling period (P Ͻ 0.05-0.01). After high nicotine cigarette smoking, prolactin increased to hyperprolactinemic levels within 6 min and remained significantly above baseline levels for 42 min (P Ͻ 0.05-0.03). The rapid increases in LH and reports of subjective "high" after both i.v. cocaine and high nicotine cigarette smoking illustrate the similarities between these drugs and suggest a possible contribution of LH to their abuse-related effects.

Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine dependence provided informed consent. After overnight abstinence from smoking, men smoked three low-or high-nicotine cigarettes for 4 min each at 60 min intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS) ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20, 30, 40, and 50 min after each cigarette. After low-nicotine cigarettes, nicotine levels, adrenocorticotropin hormone, and heart rate did not increase significantly, cortisol and dehydroepiandrosterone decreased significantly, and positive VAS ratings were lower but parallel to ratings after high-nicotine cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased monotonically. HPA axis hormones increased after smoking, but peak levels did not differ significantly after successive high-nicotine cigarettes. Positive VAS ratings and heart rate increased after each high-nicotine cigarette, but peak levels were lower after smoking the second and third cigarette. 'Craving' decreased significantly after smoking both low-and high-nicotine cigarettes, then gradually increased during the 60 min interval between cigarettes. These data are consistent with clinical reports that the first cigarette after overnight nicotine abstinence is most salient. Tolerance to the subjective and cardiovascular effects of nicotine developed rapidly during repeated cigarette smoking, but nicotine-stimulated increases in HPA axis hormones did not change significantly.