Stress is associated with drug craving and relapse in substance-dependent individuals. Hormones released from the brain may mediate the behavioral response to stress. For example, several studies have indicated that oxytocin reduces stress in laboratory stress paradigms. Specifically, it appears that oxytocin promotes trust, social interaction, and calmness; yet, little is known about the potential affects of oxytocin in cocaine-dependent individuals. Given these properties of oxytocin, it may have a therapeutic role in ameliorating the negative affect commonly observed prior to relapse in cocaine-dependent individuals, as well as the anxiety associated with withdrawal. This pilot protocol will provide important preliminary data on the effect of oxytocin on stress in cocaine-dependent individuals.

1) General Inclusion / Exclusion Criteria Inclusion Criteria

1. Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
2. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the CTRC admission. Nicotine dependence can affect HPA function therefore it would be ideal to exclude subjects with nicotine use. Because of the high comorbidity of cocaine and nicotine dependence, this would seriously compromise the feasibility of recruitment. In addition, because of the high comorbidity of alcohol use and cocaine dependence, individuals with alcohol abuse and dependence will be included if they do not require medically supervised detoxification. Due to the high comorbidity of cocaine and marijuana dependence, individuals with marijuana dependence will be included.
3. Subjects must consent to random assignment.
4. Subjects must consent to outpatient admission to the CTRC.

Exclusion Criteria

1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
2. Women with premenstrual dysphoric disorder as this may impact on the response to the stress test procedure.
3. 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 physiological/subjective responses.
4. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status.
5. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements.
6. Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response.
7. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with hormonal measurements within one month of test session.
8. Subjects taking any psychotropic medications, opiates or opiate antagonists because these may affect test response. Subjects who have been maintained on SSRI's for 8 weeks will not be excluded.
9. Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
10. Subjects who are > 30% over ideal weight or have a BMI greater than 35 will be considered for study participation based on the clinical judgment of study staff.
11. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for three days prior to the stress task procedure.
12. Subjects meeting DSM-IV criteria for substance dependence (other than alcohol, nicotine, marijuana orcocaine) within the past 60 days.