Gender and Neural Substrates of Stress and Craving
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric, Pulmonary |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 5/9/2018 |
| Start Date: | February 2009 |
| End Date: | August 2010 |
Exploring Gender Differences in the Neural Substrates of Stress Induced Drug Craving
Cocaine dependence is an insidious disease underscored by a powerful proclivity to relapse
despite an individual's ability to recognize the deleterious consequences of continued drug
use. To date, there are only a limited number of treatments, and no FDA approved medications
for the treatment of cocaine dependence. Attempts to find reliable and successful treatments
for cocaine dependence may be marred by gender differences in brain chemistry, structure, and
function that are manifested as drug craving and relapse. For example, cues, drug exposure,
and stress promote relapse, yet females appear be more susceptible to stress induced relapse,
while males may be more susceptible to cue induced relapse. Therefore identifying the neural
substrates involved in processing the valence of internal and external stimuli may provide
further insight into cocaine dependence and provide more effective therapeutic strategies
aimed at preventing relapse.
Corticotropin releasing hormone (CRH) is a pharmacological activator of the hypothalamic
pituitary adrenal (HPA) axis, and has been implicated in stress induced drug relapse.
Corticotropin releasing hormone receptors are located at extrahypothalamic brain nuclei that
have been implicated in determining the significance of both internal (somatic) and external
(environmental) stimuli. The primary directive of this pilot project is to utilize functional
magnetic resonance imaging (fMRI) to identify possible brain nuclei associated with with
stress induced drug craving in cocaine dependent females.
despite an individual's ability to recognize the deleterious consequences of continued drug
use. To date, there are only a limited number of treatments, and no FDA approved medications
for the treatment of cocaine dependence. Attempts to find reliable and successful treatments
for cocaine dependence may be marred by gender differences in brain chemistry, structure, and
function that are manifested as drug craving and relapse. For example, cues, drug exposure,
and stress promote relapse, yet females appear be more susceptible to stress induced relapse,
while males may be more susceptible to cue induced relapse. Therefore identifying the neural
substrates involved in processing the valence of internal and external stimuli may provide
further insight into cocaine dependence and provide more effective therapeutic strategies
aimed at preventing relapse.
Corticotropin releasing hormone (CRH) is a pharmacological activator of the hypothalamic
pituitary adrenal (HPA) axis, and has been implicated in stress induced drug relapse.
Corticotropin releasing hormone receptors are located at extrahypothalamic brain nuclei that
have been implicated in determining the significance of both internal (somatic) and external
(environmental) stimuli. The primary directive of this pilot project is to utilize functional
magnetic resonance imaging (fMRI) to identify possible brain nuclei associated with with
stress induced drug craving in cocaine dependent females.
Inclusion Criteria:
1. Age 18-65
2. Right-handed
3. Males and females meeting criteria for cocaine dependence (DSM-IV), within the past
three months (current).
4. Subjects must be able to provide informed consent and function at an intellectual
level sufficient to allow accurate completion of all assessment instruments.
5. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine)
for a three-day period immediately prior to the GCRC admission. Nicotine dependence
can affect HPA function therefore it would be ideal to exclude subjects with nicotine
use. Because of the comorbidity of cocaine and nicotine dependence, this would
seriously compromise the feasibility of recruitment. Alcohol has also been known to
affect HPA function, however to enhance recruitment efforts, individuals with alcohol
dependence or abuse will be included in the study if they do not require medically
supervised detoxification.
6. Participants must have a negative breathalyzer, urine drug screen.
7. Subjects must consent to outpatient admission to the GCRC
Exclusion Criteria:
1. Subjects with evidence of or a history of significant hematological, endocrine,
cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including
diabetes, as these conditions may affect HPA axis function.
2. Subjects with any liver function test of greater than two times normal, as compromised
liver function can interfere with HPA axis activity.
3. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal
cortex likely to affect HPA axis function.
4. Subjects with a history of or current psychotic disorder or bipolar affective disorder
as these may interfere with HPA function.
5. Subjects with current major depressive disorder or post-traumatic stress disorder as
these disorders are associated with characteristic changes in HPA axis function.
6. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or
treatment with other agents, that interfere with HPA axis function within one month of
the time of testing.
7. Subjects taking opiates, opiate antagonists, or benzodiazepines. (Subjects who have
been maintained on SSRI's, anticonvulsants, or antipsychotics (for sleep only) for
more than 8 weeks or longer are NOT excluded).
8. Subjects with any acute illness or fever as this may affect HPA axis activity.
Individuals who otherwise meet study criteria will be rescheduled for evaluation for
participation.
9. Subjects who are > 30% over ideal weight or have a BMI greater than 30 will be
considered for study participation based on the clinical judgment of study staff.
10. Subjects who are unwilling to maintain abstinence from alcohol and other drugs of
abuse (except nicotine) for two days prior to the stress task procedure.
11. Persons with ferrous metal implants or pacemaker since fMRI will be used.
12. Subjects that are claustrophobic
We found this trial at
1
site
Charleston, South Carolina 29425
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