A number of studies have assessed the effects of psychoactive drugs on stress biology, the neuroadaptations resulting from chronic drug use on stress biology, and their effects on addiction risk and relapse. This review mainly covers human research on the acute effects of different drugs of abuse (i.e., nicotine, cannabis, psychostimulants, alcohol, and opioids) on the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) responses. We review the literature on acute peripheral stress responses in naïve or light recreational users and binge/heavy or chronic drug users. We also discuss evidence of alterations in tonic levels, or tolerance, in the latter relative to the former and associated changes in the phasic stress responses. We discuss the impact of the stress system tolerance in heavy users on their response to drug- and stress-related cue responses and craving as compared to control subjects. A summary is provided of the effects of glucocorticoid responses and their adaptations on brain striatal and prefrontal cortices involved in the regulation of drug seeking and relapse risk. Finally, we summarize important considerations, including individual difference factors such as gender, co-occurring drug use, early trauma and adversity and drug use history and variation in methodologies, that may further influence the effects of these drugs on stress biology.

The study examined the effects of a social stressor (Trier Social Stress Test) on 24 male and 32 female college students’ affective and physiological reactivity and their subsequent performance on a decision-making task (Iowa Gambling Task). The 56 participants were randomly assigned to a social stressor or a control condition. Compared to controls, participants in the stress condition responded with higher heart rates and skin conductance responses, reported more negative affect, and on the decision-making task made less advantageous choices. An exploratory regression analysis revealed that among men higher levels of heart rate were positively correlated with riskier choices on the Iowa Gambling Task, whereas for women this relationship was curvilinear. Exploratory correlational analyses showed that lower levels of skin conductance within the stress condition were associated with greater levels of substance use and gambling. The results suggest that the presence of a stressor may generally result in failure to attend to the full range of possible consequences of a decision. The relationship pattern between the degree of stress responding and successful decision making may be different for men and women.

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Research has shown that measures of reactivity to distress-including distress tolerance and physiological reactivity to stress-are dysregulated in women who misuse alcohol. These variables may interact and create a risk profile for young adult women, reflecting patterns of stress reactivity that confer a risk for alcohol misuse. The current study tested this hypothesis by examining the independent and interactive associations of subjective distress tolerance, behavioral distress tolerance, and physiological stress reactivity with women's alcohol misuse. The study was conducted with a sample of 91 college women recruited on a large northeastern university campus. Results showed that subjective levels of distress tolerance and physiological reactivity to stress (skin conductance reactivity, SCR), but not behavioral distress tolerance, were independently associated with alcohol misuse. In addition, subjective distress tolerance moderated the relationship between SCR and negative alcohol-related consequences. Specifically, women with low physiological reactivity (SCR) to a stressful task and greater urge to quickly rid themselves of distress (low subjective distress tolerance) endorsed a significantly greater number of adverse consequences from their alcohol use. These results extend prior findings by showing that, even among a nonclinical sample of women, lower stress reactivity in combination with low subjective distress tolerance is associated with increased risk for various drinking-related negative consequences.