Effects of Diacetylmorphine (DAM) on Brain Function and Stress Response
Condition: Opiate
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): diacetylmorphine (DAM); Placebo
Intervention type(s): Drug; Other
Intervention description(s): 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.; Saline
Other intervention name(s): heroin
Intervention MeSH terms: Heroin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Substance use disorder; Stress