Biological psychiatryJan 13, 2009

Changes in brain daily rhythms during 30 days of heroin abstinence

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Abstinent heroin addicts exhibited disruptions in the diurnal rhythms of multiple neurobiological markers over a 30-day period.

Abstinent heroin addicts demonstrated altered expression patterns of clock genes hPER1 and hPER2 compared to healthy controls.
Significant disruptions in the diurnal rhythms of cortisol, ACTH, beta-endorphin, leptin, and interleukin-2 were observed in abstinent addicts.
Changes in the expression of hPER1 and hPER2, along with hormonal disruptions, persisted throughout the 30-day observation period.
Elevated 24-hour cortisol levels and reduced levels of interleukin-2 and tumor necrosis factor were recorded during abstinence.
These neurobiological changes may be associated with prolonged withdrawal symptoms and increased risk of relapse.

Simplified

BACKGROUND: Previous studies have shown that individuals withdrawn from chronic opiate administration undergo substantial elevations of cortisol levels with blunted corticotropin (ACTH) rhythms and that these changes persist beyond the 7-10 days of acute withdrawal symptoms. However, there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence relapse susceptibility.

METHODS: Blood samples were collected from 8 healthy control subjects and 16 heroin addicts during pharmacologically unassisted withdrawal on the 3rd, 10th, and 30th days of abstinence at 3-hour intervals for 24 hours. Outcome measures were the relative expression of clock gene mRNA (hperiod1, hperiod2, hclock) and the levels of serum cortisol, plasma ACTH, beta-endorphin (beta-EP), leptin, neuropeptide Y, interleukin-2 (IL-2), and tumor necrosis factor (TNF) in these subjects.

RESULTS: Compared with healthy volunteers, abstinent addicts showed disruptions in diurnal rhythms of hPER1 and hPER2 mRNA expression, along with disruptions in diurnal rhythms of cortisol, ACTH, beta-endorphin, leptin, and IL-2 release. Several of these disruptions (hPER1, hPER2, ACTH, beta-endorphin, and IL-2) persisted for the 30-day testing period, as did elevation of 24-hour levels of cortisol and decreases in 24-hour IL-2 and TNF levels.

CONCLUSIONS: These prolonged neurobiological changes may play a role in protracted opiate withdrawal symptoms and contribute to relapse vulnerability.

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Changes in brain daily rhythms during 30 days of heroin abstinence

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