 Growing evidence supports a role for gonadal hormones in explaining the sex differences observed in stress responses as well as in the behavioral responses to cocaine Festa Quinones-Jenab, 2004; K. Carroll, Fenton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ, 2004; Lynch, 2006; Kajanti Phillips, 2006. Estrogen increases behavioral responses to cocaine, while presence of progesterone decreases subjective and behavioral effects of cocaine, more so in females than males Jackson et al., 2006; Sofuogu et al., 1999; M. Sofuoglu et al., 2002; Evans Foltin, 2006. Stress and cocaine each enhance brain stress circuits, namely the corticotrophin releasing factor CRF-hypothalamic-pituitary-adrenal HPA axis and central noradrenergicsympatho-adrenomedullary SAM pathways and both activate the mesolimbic dopaminergic systems involved in the rewarding effects of cocaine ADD REFS. Exposure to Stress, cocaine or cocaine cues will each increase cocaine craving and HPA axis responses. Importantly, progesterone which affects behavioral responses to cocaine, also plays a key role in stress regulation. However, it is not known whether progesterone alters stress-induced and drug cue-induced craving and related stress arousal, markers that predict cocaine relapse outcomes. Our preliminary data suggest that women exposed to stress and to drug cues in the laboratory during the luteal phase high progesterone show lower stress induced and drug cue-induced craving, anxiety and cortisol responses compared to those in the late follicular phase high estrogen see preliminary Studies section CX. On the basis of this previous research, we propose a double-blind placebo controlled study of to examine progesterones effects on stress and cue-related responses in cocaine dependent men and women. We hypothesize that high dose of progesterone 200 mg bid vs. placebo will alter stress-induced cocaine craving, negative affect, physiological and HPA responses to stress, and these changes will be greater in women than men. 