Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence: A [11C]-(+)-PHNO PET Investigation

Conditions
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Cocaine-Related Disorders, Cocaine Addiction, Substance-Related Disorders

Intervention / Treatment
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* Drug: Corticotropin-Releasing Hormone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cocaine-dependent (CD)<br>cocaine-dependent individuals | Drug: Corticotropin-Releasing Hormone<br>* 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.<br>* Other names: corticorelin;|
| healthy control (HC)<br>healthy age and sex-matched individuals who do not use cocaine | Drug: Corticotropin-Releasing Hormone<br>* 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.<br>* Other names: corticorelin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET measure: [11C]-(+)-PHNO binding | [11C]-(+)-PHNO binding on two occasions (following corticorelin and saline) | within a month following enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stress hormone levels | plasma cortisol, ACTH | in conjunction with PET | 
| subjective measures | subjective stress, craving, mood, drug effects | in conjunction with PET | 
| vital signs | heart rate, blood pressure | in conjunction with PET | 
| neuropsychological battery | battery of neuropsychological tasks to assess cognitive function, general intelligence, and personality. | once following PET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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