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Psychoneuroendocrinology. 2009 Sep;34(8):1198-207. doi: 10.1016/j.psyneuen.2009.03.007. Epub 2009 Apr 16.

Elevated cortisol and learning and memory deficits in cocaine dependent individuals: relationship to relapse outcomes.

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Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, 2 Church Street South, Suite 209, Room 209Q, New Haven, CT 06519, USA.



Cocaine dependence is characterized by stress system dysregulation, including elevated cortisol activity, emotional negativity, and behavioral disinhibition. High levels of stress and glucocorticoids are also known to affect learning, memory and executive function. Therefore, we examined the relationships between chronic cocaine use, elevated distress and learning and memory dysfunction in abstinent cocaine dependent (CD) individuals, and whether these measures were associated with cocaine relapse outcomes.


Stress was assessed in 36 inpatient treatment engaged CD individuals and 36 demographically matched healthy control (HC) participants using the Perceived Stress Scale (PSS) and repeated morning salivary cortisol levels over three consecutive days. The Rey Auditory Verbal Learning Test (RAVLT) was conducted to measure verbal learning, memory, and executive function. Prospective assessment of cocaine use outcomes during 90 days following discharge from inpatient treatment was also conducted.


CD patients showed higher levels of distress compared to controls in PSS scores and cortisol levels. They also demonstrated a significantly reduced learning curve, and fewer correct responses and more errors on recognition. Elevated cortisol was significantly associated with worse RAVLT performance in CD patients. Poor memory scores, but not distress measures, were significantly associated with greater cocaine use after inpatient treatment.


These findings are the first to demonstrate that learning and memory deficits in CD individuals are associated with enhanced cortisol and with cocaine use outcomes after inpatient treatment. The findings are consistent with recent addiction models suggesting that chronic cocaine-related neuroadaptations affects learning and memory function, which in turn, influences drug use outcomes.

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