Background: Cocaine dependence is associated with high rates of relapse. Stress and drug cue exposure are known to increase cocaine craving and stress arousal, but the association between these responses and cocaine relapse has not been previously studied.

Objective: To examine whether stress-induced and drug cue-induced cocaine craving and hypothalamic-pituitary-adrenal axis responses evoked in the laboratory are associated with subsequent cocaine relapse.

Design: Prospective study design assessing cocaine relapse and drug use during a 90-day follow-up period after discharge from inpatient treatment and research. Data were analyzed by Cox proportional hazards regression and multiple regression.

Setting: Inpatient treatment and research unit in a community mental health center.

Patients: Forty-nine treatment-seeking cocaine-dependent individuals.

Main outcome measures: Time to cocaine relapse, number of days of cocaine use, and amount of cocaine used per occasion in the follow-up phase.

Results: Greater stress-induced, but not drug cue-induced, cocaine craving was associated with a shorter time to cocaine relapse. Stress-induced corticotropin and cortisol responses predicted higher amounts of cocaine use per occasion in the 90-day follow-up.

Conclusions: These results demonstrate that stress-related increases in cocaine craving and hypothalamic-pituitary-adrenal axis responses are each associated with specific cocaine relapse outcomes. The findings support the use of stress-induced drug craving and associated hypothalamic-pituitary-adrenal axis responses to evaluate cocaine relapse propensity. Furthermore, treatments that address stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses could be of benefit in improving relapse outcomes in cocaine dependence.