Time-dependent neuroendocrine alterations and drug craving during the first month of abstinence in heroin addicts

Am J Drug Alcohol Abuse. 2009;35(5):267-72. doi: 10.1080/00952990902933878.


Rationale: Heroin use and withdrawal cause abnormality in the endocrine system. However, the time course of neuroendocrine alterations in heroin addicts during pharmacologically unassisted withdrawal is still unclear.

Objectives: To investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of abstinence in heroin addicts.

Methods: Twelve heroin addicts and eight matched healthy control subjects were recruited for this study. The neuroendocrine alterations and self-reported heroin craving, anxiety, and depression in heroin addicts were assessed at different time points (days 3, 10, and 30) of first month of abstinence from heroin use.

Results: Self-reported heroin craving, anxiety, and depression in heroin addicts decreased gradually during the first month of abstinence. The cortisol levels increased from abstinence day 3 to 30, while ACTH and beta-EP levels decreased over this period in heroin addicts. The leptin and NPY levels were significantly decreased on days 3 and 10 but had normalized on day 30 of abstinence. A positive correlation between cortisol level and heroin craving, anxiety, and depression was observed, while a negative correlation was observed between beta-EP level and craving and anxiety and between leptin and depression and NPY and anxiety.

Conclusions: Abnormal alterations in the neuroendocrine system, including levels of cortisol, ACTH and beta-EP persist throughout the first month of abstinence. These results suggest that neuroendocrine system dysfunctions in heroin abusers is independent of the acute and protracted withdrawal syndromes, and may thus contribute to relapse to heroin use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Analysis of Variance
  • Anxiety / chemically induced
  • Case-Control Studies
  • Depression / chemically induced
  • Heroin / adverse effects*
  • Heroin Dependence / blood*
  • Humans
  • Hydrocortisone / blood
  • Leptin / blood
  • Male
  • Neuropeptide Y / blood
  • Neurosecretory Systems
  • Patient Selection
  • Psychiatric Status Rating Scales
  • Radioimmunoassay
  • Substance Withdrawal Syndrome / blood*
  • Time Factors
  • beta-Endorphin / blood


  • Leptin
  • Neuropeptide Y
  • beta-Endorphin
  • Heroin
  • Adrenocorticotropic Hormone
  • Hydrocortisone