Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men

Alcohol Clin Exp Res. 2000 May;24(5):651-8.


Background: This study tested cortisol responses to a psychological stressor in controls (CT) versus patients who were diagnosed as alcohol dependent (AD) or alcohol and stimulant dependent (ADSD) by DSM-IV criteria and who were abstinent for 3 to 4 weeks from alcohol and illicit drugs. Alcohol increases cortisol secretion acutely and during withdrawal. However, there is little information about abnormalities of hypothalamic-pituitary-adrenocortical (HPA) reactivity in recovering alcoholics.

Methods: Accordingly, we tested HPA function in the laboratory between 7:00 and 9:30 AM on control versus stress days. Stress consisted of a 20-min public speaking challenge with preparation and delivery of two short speeches, ostensibly evaluated for quality of delivery, whereas control involved relaxing for the same period. Cortisol was measured in saliva collected at baseline, stress or control, and recovery period, and also at home at 9:00 PM on one of the two days.

Results: The three groups did not differ in diurnal patterns of cortisol secretion on the rest day and 9:00 PM sample, which indicated that AD and ADSD patients had intact diurnal HPA regulation at rest. During speech stress, the CT subjects showed the expected cortisol increase (p < 0.0001), whereas neither AD nor ADSD patients responded significantly. Cortisol values were not accounted for by covariates such as depression, posttraumatic stress disorder, glucose metabolism, or anthropometric or demographic characteristics.

Conclusions: The apparent stress hyporesponsiveness of the AD and ADSD patients suggests a persistent disruption of HPA function, perhaps due to incomplete recovery from prior abuse, or to a preexisting alteration in neural systems that regulate HPA responses to stress.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alcoholism / metabolism*
  • Alcoholism / psychology
  • Analysis of Variance
  • Biomarkers / blood
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / metabolism
  • Saliva / metabolism
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / psychology
  • Temperance / psychology


  • Biomarkers
  • Hydrocortisone