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[30] Some cocaine-dependent patients may bear a greater burden of morbidity as a result of individual propensity to stress dysregulation.[7, 31-33] Thus patients coming to treatment, indistinguishable in terms of baseline cocaine severity, may have different likelihood of attaining abstinence due to differences in stress sensitivity, as did 48% of patients with atypical cortisol secretion in our sample. ��Total cortisol�� at baseline, contrary to when measured during a stress challenge,[4] may not be a sensitive marker of stress dysregulation given the wide range of ��normal�� values.[34] Non-suppression to the DST was only found in 19% (12/64) of patients, equally distributed between groups (6/12). Its significance in addiction is a matter for further BMS-777607 supplier study. There are several limitations to this study. One is the procedure whereby patients collected saliva samples without direct supervision: 85% of the samples collected were usable. Reports using similar outpatient collection methods exist in the mental health, psychology, and cancer literature.[14, 35, 36] Second, active cocaine use during saliva collection could simulate an atypical profile if it raised the afternoon cortisol levels. Since ? of the atypical, and ? of the typical samples were collected during abstinence, the data likely represents an amalgam of chronic and acute effects of cocaine. That said, our report also shows that such collection procedures can be accomplished in outpatient settings, and can collect valuable information on patients coming to treatment. Third, our procedure of evaluating Neratinib concentration baseline cortisol secretion as an index of stress dysregulation was not compared to stress sensitivity measures in the laboratory. RVX-208 Such a comparison could possibly bring findings from cortisol secretion profile more in line with existing studies of stress sensitivity in cocaine dependent patients. Fourth, the data analysis used established categorical measures in keeping with the existing literature rather than continuous analyses, which may have revealed more details on the relationship between cocaine dependence and stress dysregulation. Despite these limitations, we have presented evidence that depressed cocaine-dependent patients with atypical diurnal cortisol secretion face greater difficulty in reaching early abstinence, a key predictor of subsequent treatment success. We also propose that atypical cortisol secretion may indicate stress dysregulation in cocaine dependence. If stress dysregulation could be rectified when present, this may improve cocaine treatment outcome. Some evidence exists for this. Attenuation of the sympathetic nervous system arm of the stress response with alpha-2 adrenergic receptor agonists can reduce relapse risk following treatment for cocaine dependence.[37] Results from ongoing investigations may provide supporting evidence for this approach to treat cocaine dependence.