Cocaine Addiction, Cocaine-Related Disorders, Substance-Related Disorders
Conditions
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
Brief 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.
Interventions
DRUGCorticotropin-Releasing Hormone
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.
Sponsors
Centre for Addiction and Mental Health
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PET measure: [11C]-(+)-PHNO binding | within a month following enrollment | \[11C\]-(+)-PHNO binding on two occasions (following corticorelin and saline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| stress hormone levels | in conjunction with PET | plasma cortisol, ACTH |
| subjective measures | in conjunction with PET | subjective stress, craving, mood, drug effects |
| vital signs | in conjunction with PET | heart rate, blood pressure |
| neuropsychological battery | once following PET | battery of neuropsychological tasks to assess cognitive function, general intelligence, and personality. |
Countries
Canada
Outcome results
None listed