Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence
Condition: Cocaine-Related Disorders; Cocaine Addiction; Substance-Related Disorders
MeSH terms: Cocaine-Related Disorders; Substance-Related Disorders; Behavior, Addictive
Study type: Observational

Summary: 
      This study will, in a sample of cocaine-dependent and healthy control subjects, administer
      corticorelin and compare dopamine release between groups. Dopamine release will be measured
      using PET neuroimaging with the radiotracer [11C]-(+)-PHNO.
    

Detailed description: 
      SCIENTIFIC SUMMARY The project will, in a sample of cocaine-dependent (CD) and healthy
      control (HC) subjects, use administration of Corticorelin, a synthetic form of corticotropin
      releasing factor (CRF)and PET imaging to assess dopamine (DA) transmission in addiction. We
      will use [11C]-(+)-PHNO PET to measure striatal DA receptor binding on two occasions: 1)
      following corticorelin administration and 2) following saline. The change in receptor binding
      between the two occasions (i.e., displacement of [11C]-(+)-PHNO by endogenous DA) will index
      DA release.

      SUBJECTS CD subjects will meet DSM-IV criteria for abuse or dependence and be ~10d cocaine
      abstinent at the time of PET. HC will be recruited to match CD on age, sex, education, and
      cigarette smoking.

      PRIMARY OUTCOME MEASURES We will measure [11C]-(+)-PHNO binding on two occasions
      (corticorelin, saline), with the difference between conditions indexing dopamine release;
      this measure will then be compared between cocaine-dependent and control subjects. We will
      also measure plasma cortisol and ACTH), physiological measures, and subjective craving and
      mood.
    

Intervention name(s): Corticotropin-Releasing Hormone
Intervention type(s): Drug
Intervention description(s): Each subject will receive a single dose of Corticotropin-Releasing Hormone corticorelin on a single occasion, and a volume-matched saline injection on a second occasion. Corticorelin will be administered as an intravenous infusion over a 30- to 60-second interval at a dose of 1 ug/kg body weight. ~15 minutes after Corticorelin/saline injection, [11C]-(+)-PHNO will be administered followed by 90 minutes of PET scanning. Primary outcome measure ([11C]-(+)-PHNO) as well as Secondary outcome measures (self reported feeling, hormones and physiological measures) will be obtained before saline or Corticorelin/saline injection and for 90-120 minutes following injection.
Other intervention name(s): corticorelin
Intervention MeSH terms: Hormones; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        CD subjects are recruited from the local community using flyers and internet
        advertisements, and through referral from local clinical programs. CD subjects are
        recruited from the community using flyers and internet advertisements.
      
Biospecimen description: 
      whole blood
    
Keywords: Cocaine; Substance-Related Disorders; Drug Addiction; Substance Addiction; Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Stress, Psychological; Corticorelin; Neuroendocrine System; Cortisol; Adrenocorticotropic Hormone; Positron-Emission Tomography; 11C-PHNO