HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study

Drug Alcohol Depend. 2009 Dec 1;105(3):202-8. doi: 10.1016/j.drugalcdep.2009.06.026. Epub 2009 Aug 26.


Introduction: Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment.

Method: Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure.

Results: The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout.

Conclusions: Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / metabolism*
  • Male
  • Mental Disorders / complications
  • Middle Aged
  • Patient Dropouts / psychology
  • Pituitary-Adrenal System / metabolism*
  • Prospective Studies
  • Residential Treatment
  • Saliva / metabolism
  • Stress, Psychological / metabolism*
  • Substance-Related Disorders / complications
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / therapy*
  • Treatment Failure


  • Hydrocortisone