Acute effects of heroin on emotions in heroin‐dependent patients

Blum, Julia E.; Gerber, Helmut; Gerhard, Urs; Schmid, Otto; Petitjean, Sylvie; Riecher-Rössler, Anita; Wiesbeck, Gerhard A.; Borgwardt, Stefan; Walter, Marc

doi:10.1111/j.1521-0391.2013.12025.x

Cited by 37 publications

(28 citation statements)

References 41 publications

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“…Furthermore, we recently observed that patients even revealed increased state-anxiety and craving scores after the injection of saline [3], indicating an experimentally induced state of acute withdrawal. There is an extensive body of data available that has investigated changes in global methylation in heroin-dependent patients [4] and the methylation of POMC and NR3C1 in the context of substance-related addiction (e.g., to alcohol) [6].…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…Substitution predictably resolves craving-induced stress and anxiety, making the individual compliant to other forms of therapy [2]. In previous reports, DAM-assisted treatment was consistently found to be an effective treatment for severe heroin dependence [3-5]. …”

Section: Introductionmentioning

confidence: 99%

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

Groh¹,

Rhein²,

Buchholz³

et al. 2017

Neuropsychobiology

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“…In particular, resting-state connectivity strengths in this network were compared between 20 heroin-dependent patients after receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Although all patients are actively enrolled in a maintenance therapy, acute heroin substitution still induces positive emotions and a feeling of rush in these patients, 24, 25 indicating that positive reinforcement effects continue during protracted maintenance treatments. Here, we examined whether these subjective rewarding effects after heroin substitution were mediated via connectivity changes in the basal ganglia/limbic network.…”

Section: Introductionmentioning

confidence: 99%

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

et al. 2015

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Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

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“…This reduced perfusion in these areas may underlay the feelings perceived by heroin users, such as relaxation and euphoria [49]. The mPFC and ACC are both parts of the cortical midline structures and the default mode network (DMN) [34].…”

Section: Discussionmentioning

confidence: 99%

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

et al. 2013

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Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment.

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Acute effects of heroin on emotions in heroin‐dependent patients

Abstract: Heroin dampens craving, negative emotions, and increases positive emotions. These findings indicate that heroin regulates emotions and underscore the clinical benefit of opioid substitution treatment for heroin-dependent patients.

Cited by 37 publications

References 41 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>

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

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