Hypothalamic-pituitary-adrenocortical responses to psychological stress and risk for smoking relapse.

Stress is a commonly reported precipitant of relapse to substance use. There is a growing recognition of the need to understand psychobiological alterations in the stress response among chronic drug users, and to determine how they may precipitate relapse. This paper focuses on the hypothalamic-pituitary-adrenocortical (HPA) response to stress among dependent smokers. Nicotine acutely activates the HPA axis, and increased HPA activity has been linked to attenuated CNS nicotinic receptor sensitivity. We will review a series of studies demonstrating that steep decline in cortisol concentrations during early abstinence and hyporesponsiveness to stress predict shorter time to relapse. Our studies show that hormonal associations with smoking relapse tend to be more consistent in men, while intensity of withdrawal symptoms tend to be consistent predictors of smoking relapse in women. We propose that perturbed HPA activity during early smoking abstinence exacerbate withdrawal symptoms and may contribute to the rapid relapse observed in the majority of smokers. Our results also reinforce the need for gender-specific investigation of mechanistic and interventional strategies to combat nicotine addiction.