Oxytocin in Cocaine Dependence

Stress is an important predictor of relapse, and targeting stress-activated pathways may lead to therapeutic advancements in the treatment of substance use disorders. Oxytocin has been shown to promote trust, social bonding, and calmness; however, its potential effects have not been explored in cocaine-dependent individuals. Oxytocin receptors have been localized to brain regions that are activated by drug-paired cues and preclinical studies have shown that oxytocin attenuates the acute and long-term behavioral effects of psychostimulants. However, little is known about the role of oxytocin in mediating the affective response to cocaine-paired cues and associated neural activity in cocaine-dependent men and women. This project is a direct evolution from our previous SCOR-supported research. Our work has progressed from characterizing sex/gender differences in response to social stressors and cocaine cues in cocaine-dependent men and women, to our on-going work evaluating whether stress potentiates cue-induced craving and the impact of hormones on this response. The proposed study will investigate the role of oxytocin in the sex/gender differences in stress response and craving in cocaine-dependent individuals and preliminarily explore its therapeutic potential.

Inclusion criteria

• Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
• Subjects must meet DSM-IV criteria for current cocaine dependence (within the past three months). While individuals may also meet criteria for abuse of other substances, they must not meet criteria for dependence on any other substance (except nicotine) within the last 60 days. Alcohol has been known to affect HPA function (Adinoff et al., 1991), 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. Also, due to the high comorbidity of cocaine and marijuana dependence, and limited evidence that marijuana use affects HPA function, subjects with marijuana dependence will be included.
• Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the throughout study procedures.
• Subjects must consent to random assignment.
• Subjects must consent to participating in study procedures at the ASD and completion of two fMRI scans.

Exclusion criteria

• Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control (not including hormonal contraceptives).
• Women who are currently taking, or have taken in the past month, oral or other types of hormonal contraceptives or hormone replacement therapies.
• Women with premenstrual dysphoric disorder who are outside of the follicular phase.
• Women who have had a complete hysterectomy or are over 50 over one year post-menopausal, as ovarian hormones will be measured in the study.
• 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. Neurological exclusions include history of stroke, seizure disorders, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.
• Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status.
• Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements.
• Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response.
• 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.
• Subjects taking any mood stabilizers, antipsychotics, benzodiazepines, opiates or opiate antagonists because these may affect test response. Subjects taking SSRI's will be included.
• Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
• Subjects whose height to weight ratio would preclude them from fitting comfortably in the MRI scanner.
• 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.
• Persons with ferrous metal implants or pacemaker since fMRI will be used.
• Subjects who are claustrophobic.
• Subjects with significant psychiatric or medical problems that would impair participation or limit ability to participate in scan.
• Subjects who require maintenance or acute treatment with any psychoactive medication including anti-seizure medications which could potentially interfere with fMRI.
• Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, cocaine, alcohol or marijuana) within the past 60 days.