The effect of transdermal nicotine on stress reactivity was investigated in  currently smoking, detoxified, substance-dependent individuals (65% alcohol  dependent, n = 51; 31 male) following a psychosocial stressor.
 Using a randomized, double-blind, placebo-controlled  design, subjects were assigned to receive either active transdermal nicotine  (low or high dose) or placebo. Six hours following nicotine administration,  subjects performed a laboratory psychosocial stressor consisting of two 4-min  public-speaking sessions.
 Consistent with prior  reports, substance-dependent individuals displayed a blunted stress response.  However, a review of the cortisol distribution data encouraged additional  analyses. 
Notably, a significant minority of the substance-dependent individuals  (33%) demonstrated elevated poststress cortisol levels. This group of responders  was more likely to be alcohol dependent and to have received the high dose of  nicotine [χ2(2) = 32, P < 0.0001],  [χ2(2) = 18.66, P < 0.0001]. Differences in salivary  cortisol responses between responders and nonresponders could not be accounted  for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive  symptomatology at the time of the psychosocial stressor. 
These results suggest that nicotine administration  may support a normalization of the salivary cortisol response following  psychosocial stress in subgroups of substance-dependent individuals,  particularly those who are alcohol dependent. Given the association between  blunted cortisol levels and relapse, and the complex actions of nicotine at  central and peripheral sites, these findings support the systematic study of  factors including nicotine, which may influence stress reactivity and the  recovery process in alcohol-dependent individuals. 
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