The Impact of Diacetylmorphine on Hypothalamic-Pituitary-Adrenal Axis Activity and Heroin Craving in Heroin Dependence

Gerber, Helmut; Borgwardt, Stefan; Schmid, Otto; Gerhard, Urs; Joechle, Wolfgang; Riecher-Rössler, Anita; Wiesbeck, Gerhard A.; Walter, Marc

doi:10.1159/000334411

Cited by 18 publications

(13 citation statements)

References 90 publications

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“…Our group previously found suppressed cortisol concentrations and reduced craving scores after acute methadone administration in heroin-dependent patients [9]. We also demonstrated a normalized HPA axis response as well as a decrease in negative feelings such as anxiety and craving when heroin-dependent patients received their regular dose of DAM [10, 11]. This dampening effect on negative emotions highlights the regulatory effect of acute DAM administration and illustrates how compliance is maintained.…”

Section: Introductionsupporting

confidence: 63%

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

Groh¹,

Rhein²,

Buchholz³

et al. 2017

Neuropsychobiology

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The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro- opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

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Section: Introductionsupporting

confidence: 63%

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

Groh¹,

Rhein²,

Buchholz³

et al. 2017

Neuropsychobiology

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“…This dampening effect of negative affectsVincluding craving and withdrawal levelVhighlights the acute emotional regulation effect of heroin administration and may be a relevant factor in maintaining drug-taking behavior. 38 Previous studies have demonstrated the emotional regulation effect of methadone application too, but with slightly higher opioid doses. 8 Moreover, studies on intravenously injected heroin may better reflect the pattern of drug use in heroin addicts.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of Intravenous Heroin on the Hypothalamic-Pituitary-Adrenal Axis Response

Walter¹,

Gerber²,

Kuhl³

et al. 2013

Journal of Clinical Psychopharmacology

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Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

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“…On the other hand, it would be interesting to investigate if other medications for substitution, i.e. morphine or diamorphine [36], would be able to reduce NFOO, especially because diamorphine has been shown to be very effective in suppressing the stress response and craving [37]. …”

Section: Discussionmentioning

confidence: 99%

Non-Fatal Opioid Overdose and Major Depression among Street-Recruited Young Heroin Users

Chahua

Sordo²,

Barrio³

et al. 2013

Eur Addict Res

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Background/Aims: Non-fatal opioid overdose (NFOO) and major depression (MD) are highly prevalent in heroin users. Many risk factors are known for NFOO, but studies in non-clinical samples on its relationship with MD are lacking. We aimed to examine this relationship in a street-recruited sample, controlling for potential well-known confounders. Methods: A cross-sectional study in 452 heroin users street-recruited by chain referral methods in three Spanish cities. Eligibility criteria were: age ≤30 years, heroin use at least 12 days in the last year and at least once in the last 3 months. Depression was assessed using the Composite International Diagnostic Interview. A precise definition of NFOO was used. Adjusted odds ratios (AORs) for the NFOO predictors were obtained by logistic regression. Results: The prevalence of NFOO and MD in the last 12 months was 9.1 and 23.2%, respectively. After adjusting for potential confounders, NFOO and MD were significantly associated (AOR 2.2; 95% CI 1.01-4.74). Other associated factors were imprisonment (AOR 4.1; 95% CI 1.4-12.1), drug injection (AOR 6.7; 95% CI 2.4-18.4) and regular use of tranquillisers/sleeping pills (AOR 2.9; 95% CI 1.16-7). Conclusions: Drug and mental health treatment facilities should consider the relationship between MD and NFOO when contacting and treating heroin users. Imprisonment, drug injection and use of tranquillisers/sleeping pills are also risk factors for NFOO.

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The Impact of Diacetylmorphine on Hypothalamic-Pituitary-Adrenal Axis Activity and Heroin Craving in Heroin Dependence

Cited by 18 publications

References 90 publications

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of <b><i>POMC</i></b> and <b><i>NR3C1</i></b>

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of <b><i>POMC</i></b> and <b><i>NR3C1</i></b>

Acute Effects of Intravenous Heroin on the Hypothalamic-Pituitary-Adrenal Axis Response

Non-Fatal Opioid Overdose and Major Depression among Street-Recruited Young Heroin Users

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