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.

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.

Inclusion Criteria:

• Sign and date informed consent
• Willing and able to complete trial as described in the protocol
• Psychiatrically healthy (as per diagnostic interview) except for cocaine dependence in cocaine users and nicotine dependence in both groups
• Mentally healthy
• Medically healthy (as per medical exam) with no current use of medications that may interfere with hormone activity or psychological measurements

Exclusion Criteria:

• Axis I psychiatric disorder (as per diagnostic interview), or medical condition that might interfere with participation in the study (as per medical exam)
• Exposure to radiation in the last 12 months exceeding the amount permissible by the CAMH PET centre
• Have received synthetic glucocorticoid or exogenous steroid therapy within one month of testing
• Exceed normal body weight
• If female: pregnancy or breast-feeding
• Metal implants or paramagnetic objects contained within the body
• Claustrophobia

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.