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The effects of diacetylmorphine (heroin) on human brain function and stress response

English title The effects of diacetylmorphine (heroin) on human brain function and stress response
Applicant Walter Marc
Number 127544
Funding scheme Project funding (Div. I-III)
Research institution Universitäre Psychiatrische Kliniken Universität Basel
Institution of higher education University of Basel - BS
Main discipline Neurology, Psychiatry
Start/End 01.02.2010 - 31.01.2012
Approved amount 220'666.00
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Keywords (7)

Heroin; Diacetylmorphine; Functional magnetic resonance imaging (fMRI); Stress; Heroin dependence; Personality disorder; functional magnetic resonance imagin

Lay Summary (English)

Lead
Lay summary
Heroin dependence (HD) is a chronic relapsing brain disorder that is defined by a compulsion to seek and use heroin, and a loss of control in limiting intake. Stress is a key factor for relapse in heroin-dependent patients. The prescription of diacetylmorphine (heroin) itself for maintenance has become an established treatment in several European countries. However, the neurobiological effects of diacetylmorphine (DAM) on brain function and stress response have not been studied so far. Imaging the acute effects of DAM administration during stress stimuli would elucidate the neurocircuitry and neurobiology of substance use in patients with HD. We expect that DAM attenuates the engagement of brain regions involved in response inhibition and emotional processing. Additionally, we hypothesize that DAM reduces stress response (cortisol, heart rate, skin conductance) to emotional and cognitive stimuli. To investigate the effect of DAM on brain using functional magnetic resonance imaging (fMRI), coupled with measurements of cortisol concentrations and neurophysiological stress parameters during the presentation of emotional and cognitive stimuli in patients with HD. Thirty heroin-dependent patients on stable heroin maintenance will be examined in a randomized placebo-controlled crossover design. They will be compared with 30 heroin-dependent age- and gender-matched but otherwise healthy volunteers receiving placebo. The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or placebo through an indwelling intravenous line. Afterwards they will complete four experimental paradigms testing response inhibition and emotional processing while brain responses are measured with fMRI. Before and after the fMRI investigation cortisol samples, DAM blood levels, neurophysiological and psychological stress parameters, such as skin conductance, heart rate, anxiety, anger, and heroin craving will be measured. DAM effects on brain function and stress will advance our understanding of the mechanisms underlying HD. It is the first neuroimaging study investigating the neural basis of HD after intravenous DAM administration in humans. Determining the neurofunctional and neurophysiological basis of heroin dependence may facilitate clinical diagnosis and improve clinical interventions such as prevention and treatment.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution
Andre Schmidt Niklaus Denier Undine Lang Stefan Borgwardt Marc Walter (2015), Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution, in Transl Psychiatry, 24(5), 533.
Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity
Schmidt André Walter Marc ... Borgwardt S (2015), Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity, in Brain, 138(1), 217-228.
Orbitofrontal response to drug-related stimuli after heroin administration.
Marc Walter (2015), Orbitofrontal response to drug-related stimuli after heroin administration., in Addiction Biology, 20(3), 570-579.
Altered prefrontal connectivity after acute heroin administration during cognitive control
Andre Schmidt Marc Walter (2014), Altered prefrontal connectivity after acute heroin administration during cognitive control, in The International Journal of Neuropsychopharmacology , 17(9), 1375-1385.
Acute effects of intravenous diacetylmorphine on the hypothalamic-pituitary-adrenal axis response
Marc Walter (2013), Acute effects of intravenous diacetylmorphine on the hypothalamic-pituitary-adrenal axis response, in J Clin Psychopharmacol, 33(2), 193-198.
Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study.
Denier Niklaus, Schmidt André, Gerber Hana, Riecher-Rössler Anita, Wiesbeck Gerhard, Huber Christian, Lang Undine E, Radue Ernst-Wilhelm, Walter Marc, Borgwardt Stefan (2013), Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study., in Front. Psychiatry, 1-7.
Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control
Schmidt André, Walter Marc, Gerber Hana, Schmid Otto, Smieskova Renata, Bendfeldt Kerstin, Wiesbeck Gerhard A., Riecher-Rössler Anita, Lang Undine E., Rubia Katya, McGuire Philip, Borgwardt Stefan (2013), Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control, in Neuropsychopharmacology, 38(11), 2231-2239.
Reduction in cerebral perfusion after heroin administration: a resting state arterial spin labeling study
Denier Niklaus, Gerber Hana, Vogel Marc, Klarhöfer Markus, Riecher-Rössler Anita, Wiesbeck Gerhard A, Lang Undine E, Borgwardt Stefan, Walter Marc (2013), Reduction in cerebral perfusion after heroin administration: a resting state arterial spin labeling study, in PLoS One , e71461.
The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence
Gerber Hana, Borgwardt Stefan J., Schmid Otto, Gerhard Urs, Joechle Wolfgang, Riecher- Rössler Anita, Wiesbeck Gerhard A, Walter Marc (2012), The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence, in European Addiction Research , 18(3), 116-123.
Stress und Stressreaktivität bei der Opioidabhängigkeit – ein Überblick
Gerber Hana, Borgwardt Stefan J., Gerhard Urs, Riecher-Rössler Anita, Wiesbeck Gerhard A., Walter Marc (2011), Stress und Stressreaktivität bei der Opioidabhängigkeit – ein Überblick, in Schweizer Archiv für Neurologie und Psychiatrie, 162(6), 239-245.
Neural effects of heroin – relation to anxiety stress
Walter Marc, Wiesbeck Gerhard A., Riecher-Rössler Anita, Borgwardt Stefan J. (2010), Neural effects of heroin – relation to anxiety stress, in Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34(5), 816-817.
Acute effects of heroin on emotions in heroin-dependent patients
Blum Julia, Gerber Hana, Gerhard Urs, Schmid Otto, Petitjean Sylvie, Riecher-Rössler Anita, Wiesbeck Gerhard A., Borgwardt Stefan J., Walter Marc, Acute effects of heroin on emotions in heroin-dependent patients, in American Journal on Addictions.
Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses
Schmidt André, Borgwardt Stefan, Gerber Hana, Wiesbeck Gerhard A, Schmid Otto, Riecher-Rössler Anita, Smieskova Renata, Lang Undine E, Walter Marc, Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses, in Biol Psychiatry.
Reduced volume of the nucleus accumbens in heroin addiction.
Seifert C Walter Marc, Reduced volume of the nucleus accumbens in heroin addiction., in Eur Arch Psychiatry Clin Neurosci.

Collaboration

Group / person Country
Types of collaboration
Prof. Klaus Scheffler, Medizinische Radiologie Universitätsspital Basel Switzerland (Europe)
- Research Infrastructure
Dr. Wolfgang Jöchle, Labormedizin Universitätsspital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Rudolf Brenneisen, Universität Bern, Departement Klinische Forschung Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Dr. med. Hartmut Schächinger, Universität Trier, Institut für Psychobiologie Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Philip McGuire, King's College London, Institute of Psychiatry Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Dr. med. Helge Frieling, Klinik für Psychiatrie, Medizinische Hochschule Hannover Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Deutscher Suchtkongress 2014 Talk given at a conference Effekt der Heroinsubstitution auf stressrelevante Hirnregionen 01.10.2014 Berlin, Germany Walter Marc;
DGPPN Kongress 2011 Talk given at a conference Akute Effekte von Diacetylmorphin (Heroin) auf die Hypothalamus-Hypophysen-Nebennierenrinden (HPA)-Achse 23.11.2011 Berlin, D, Germany Riecher-Rössler Anita; Walter Marc; Gerber Hana; Wiesbeck Gerhard; Borgwardt Stefan;
Swiss Addiction Research Day V of the Swiss Society of Addiction Medicine (SSAM) Poster Acute effects of diacetylmorphine on the hypothalamic-pituitary-adrenal (HPA) axis 14.04.2011 Zürich, CH, Switzerland Riecher-Rössler Anita; Gerber Hana; Walter Marc; Borgwardt Stefan; Wiesbeck Gerhard;
European Congress of Psychiatry 2011 Talk given at a conference STRESS REACTIVITY IN PATIENTS WITH DRUG DEPENDENCE AND PERSONALITY DISORDERS 12.03.2011 Wien, Austria Gerber Hana; Wiesbeck Gerhard; Riecher-Rössler Anita; Borgwardt Stefan; Walter Marc;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Stresshormon mildert das das Verlangen nach Heroin NZZ Italian-speaking Switzerland Rhaeto-Romanic Switzerland International German-speaking Switzerland Western Switzerland 2015
Media relations: print media, online media Warum Heroin bei Drogenabhängigen den Stress dämpft Uni Basel German-speaking Switzerland 2014

Associated projects

Number Title Start Funding scheme
115193 Stress Reaktion bei Patienten mit Borderline Persönlichkeitsstörung und Alkoholabhängigkeit 01.01.2007 International short research visits

Abstract

1. SummaryBackground: Heroin dependence (HD) is a chronic relapsing brain disorder that is defined by a compulsion to seek and use heroin, and a loss of control in limiting intake. Stress is a key factor for relapse in heroin-dependent patients. The prescription of diacetylmorphine (heroin) itself for maintenance has become an established treatment in several European countries. However, the neurobiological effects of diacetylmorphine (DAM) on brain function and stress response have not been studied so far. Imaging the acute effects of DAM administration during stress stimuli would elucidate the neurocircuitry and neurobiology of substance use in patients with HD. Working hypothesis: We expect that DAM attenuates the engagement of brain regions involved in response inhibition (prefrontal and anterior cingulate cortex), emotional processing (amygdala) and working memory (frontal and mediotemporal cortex). Additionally, we hypothesize that DAM reduces stress response (cortisol, heart rate, skin conductance) to emotional and cognitive stimuli, especially in patients with HD and concomitant borderline personality disorder traits. Specific aims: To investigate the effect of DAM on brain using functional magnetic resonance imaging (fMRI), coupled with measurements of cortisol concentrations and neurophysiological stress parameters during the presentation of emotional and cognitive stimuli in patients with HD. Methods: Thirty heroin-dependent patients on stable heroin maintenance will be examined in a randomized placebo-controlled crossover design. They will be compared with 30 heroin-dependent age- and gender-matched but otherwise healthy volunteers receiving saline. The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or saline through an indwelling intravenous line. Afterwards they will complete four experimental paradigms testing response inhibition, emotional processing and working memory while brain responses are measured with fMRI. Before and after the fMRI investigation cortisol samples, DAM blood levels, neurophysiological and psychological stress parameters, such as skin conductance, heart rate, anxiety, anger, and heroin craving will be measured. Expected value of the proposed project: DAM effects on brain function and stress will advance our understanding of the mechanisms underlying HD. It is the first neuroimaging study investigating the neural basis of HD after intravenous DAM administration in humans. Determining the neurofunctional and neurophysiological basis of heroin dependence may facilitate clinical diagnosis and improve clinical interventions such as prevention and treatment.
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