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Background: Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood.Objectives: Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving.Methods: Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity.Results: The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p < 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p < 0.01). Similar effects were found for cocaine craving in men (p < 0.0001).Conclusion: EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences. [ABSTRACT FROM AUTHOR]