Effects of Diacetylmorphine (DAM) on Brain Function and Stress Response

The Effects of Diacetylmorphine (Heroin) on Human Brain Functions and Stress Response

The aims of the study are to investigate the effects of diacetylmorphin (heroin) 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 heroin dependence.

Study Overview

• Status: Completed
• Conditions: Opiate
• Intervention / Treatment: Other: Placebo; Drug: diacetylmorphine (DAM)

Detailed Description

Background: 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.

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: The investigators 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.

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4025
    • UPK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• opioid dependence

Exclusion Criteria:

• other psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Heroin-dependent patients_1; daily dose of diacetylmorphine (30 mg to 500 mg) in 5 ml	Drug: diacetylmorphine (DAM); The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or placebo (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.; Other Names: heroin
Placebo Comparator: Heroin-dependent patients_2; 5 ml saline	Other: Placebo; Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
brain functions	1 hour

Secondary Outcome Measures

Outcome Measure	Time Frame
stress response	pre and post stress measurements

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: University of Bern
• Investigators: Principal Investigator: Marc Walter, MD, UPK, University Hospital Basel

Publications and helpful links

Helpful Links

• clinic homepage

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: August 2, 2010
• First Submitted That Met QC Criteria: August 3, 2010
• First Posted (Estimate): August 4, 2010

Study Record Updates

• Last Update Posted (Estimate): October 15, 2015
• Last Update Submitted That Met QC Criteria: October 13, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Stress; Substance use disorder
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Heroin
• Other Study ID Numbers: DAM2010_01; SNF127544 (Other Grant/Funding Number: SNF)