Introduction: Glucocorticoid activity is disrupted in substance users including khat chewers who also use tobacco. Anger, dysphoria, and anxiety can mediate this relationship. The aim of this study was to contrast emotion dysregulation and substance use variables as predictors of post-stress cortisol output. Materials and methods: Comparable numbers of males (n = 90) and females (n = 85) including controls, khat only, and concurrent khat and tobacco users participated in a stress study. Depressive affect, anxiety, anger, substance use patterns, and saliva samples were collected following a standardized laboratory stress manipulation. Results: Regression analysis showed that high depression and low anxiety was associated with high post-stress cortisol, but only in co-users of tobacco and khat. Males, but not females, showed a significant association between co-use of khat and tobacco and cortisol, which appears to be mediated by frequency of use. The link between anxiety and post-stress cortisol in the co-users remained significant after controlling for nicotine dependence and substance use frequency. Conclusion: Anxiety predicted the neuroendocrine consequences of concurrent use of tobacco and khat above and beyond sex, nicotine dependence, anger, and substance use frequency. Sex differences, however, are related to differences in nicotine dependence.
- Depressive affect