Cue-Induced Reactivity, Cortisol Response and Substance Use Outcome in Treated Heroin Dependent Individuals

Background: Environmental stimuli associated with drug taking have been known to elicit drug craving and physiologic arousal, as well as hypothalamic-pituitary-adrenal axis activation. However, the relationship between these responses and substance use outcomes in heroin-dependent subjects has not been previously studied. We investigated the relationship among subjective and physiologic reactivity, biological stress response evoked in the laboratory, and relapse to substance use in treated opiate-dependent individuals. Methods: Eighteen opiate-abstinent methadone-or buprenorphine-treated patients and 13 control subjects were exposed to neutral-and drug-cue exposure laboratory sessions with a 3-month follow-up period. Exposure to cues involved both videotapes and handling during a 100-min session. Subjective craving, agonistic effects, withdrawal feelings, galvanic skin resistance, and salivary cortisol were assessed. Substance use outcome among patients was examined during the follow-up phase. Differences between relapsers, nonrelapsers, and controls were analyzed with respect to the data on drug-cue responsivity and on cortisol responses using repeated-measures analysis of variance. The association with substance use outcome was assessed using a nominal logistic model. Results: Relapsers experienced greater drug-cue induced subjective responses and an increased cortisol response compared with both nonrelapsers and control subjects. After adjusting on covariates, cue-induced cortisol response was associated with the relapser group and was highly correlated with self-reports of high. Conclusions: Subjects defined as relapsers presented a higher cue-induced reactivity during the drug-cue exposure as well as an increased cortisol response to drug cues. Higher cortisol response to drug cues may increase relapse vulnerability in stable-dose buprenorphine or methadone-maintained subjects.