¹Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA, USA

Correspondence: Dr JH Mendelson, Alcohol and Drug Abuse Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. Tel: +1 617 855 2716; Fax: +1 617 855 2519; E-mail: jmendel@mclean.harvard.edu

Received 26 January 2005; Revised 18 March 2005; Accepted 21 March 2005; Published online 4 May 2005.

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 (23.92.6 ng/ml) were significantly greater than after low-nicotine cigarette smoking (3.630.59 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 21.885.34 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 42448 and 21.132.55 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.