Oxytocin and Cognitive Behavioral Therapy in Drug Dependence

* INCLUSION CRITERIA: All participants must: 1. Be between age 18 and 65. 2. Methadone arm only: opiate dependence for the past year determined by clinical exam, opiate-positive urine during screening and diagnosis confirmed by SCID. 3. Cocaine outpatient arm: cocaine dependence determined by clinical exam, cocaine-positive urine during screening and diagnosis confirmed by SCID. 4. Cocaine inpatient arm: Cocaine dependence determined by clinical exam during screening and diagnosis confirmed by SCID. 5. Control participants: cocaine dependent and non-drug using, will be recruited to provide appropriate matches for subjects in the two treatment arms with respect to the following characteristics: age, gender, IQ, socioeconomic factors, and years of education. 6. Be free of dependence on other substances except nicotine, heroin (for the methadone arm only), or cocaine at the time of participation. Justification: Dependence on other substance may result in unique CNS deficits that would confound our results. Nicotine dependence will be allowed because nicotine use is not associated with a drug high in normal usage and the prevalence of nicotine dependence in cocaine users may make it impractical to exclude nicotine users. While it might be preferable to exclude individuals whose use of other substances reaches the threshold of abuse, inclusion of such individuals will not necessarily contaminate the data. Inpatient cocaine arm subjects who meet DSM-IV TR criteria for the course specifier In a Controlled Environment may have a history of dependence on substances other than cocaine before their admission to the inpatient treatment program. Assessment tool(s): SCID with confirmation by negative urine drug screen. For participation in the scanning portion of the study, participants must also: 7. Be between the ages of 18-55. Justification: Many of the cognitive processes under study change with age. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increases with age. Individuals over 55 will therefore be excluded. Assessment tool(s): driver s license, birth certificate, or other government-issued form of identification. 8. Be in good health. Justification: Many illnesses can alter fMRI signal and alter cognition. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a history and physical examination with a qualified IRP clinician (exam details discussed below in reference to specific exclusion criteria). 9. Be right-handed. Justification: Many of the brain functions to be assessed in this protocol have shown some evidence of being lateralized in the brain. In order to reduce variability in the data, participants must be right-handed. Assessment tool(s): Edinburgh Handedness Inventory. EXCLUSION CRITERIA: Participants will be excluded if they have evidence of: 1. Schizophrenia or any other DSM-IV psychotic disorder; history of bipolar disorder; current major depressive disorder. 2. Current dependence on alcohol or sedative-hypnotic, e.g. benzodiazepine (by DSM-IV criteria), except for inpatient cocaine arm. 3. Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires. 4. Renal insufficiency with serum creatinine greater than 1.7. 5. Medical illness that in the view of the investigators would compromise participation in research such as: a history of syncope, family history of sudden death, electrolyte imbalance, bradycardia, arrhythmias, marked sustained high BP with SBP \> 160 and or DBP \> 100 on more than two readings without 3rd reading being below these parameters and not stabilized on antihypertension medications before the starting the study, congestive heart failure, history or finding on screening EKG of significant abnormality such as prolonged QTc (\> 450ms) , or AIDS or HIV positive with T cell count less than or equal to 200. 6. Urologic conditions that would inhibit urine collection. 7. Untreated Endocrine disorders. 8. Pregnancy, planning to become pregnant, or breastfeeding. In addition, women of child-bearing age who are sexually active are required to use an effective form of birth control for the duration of the study. Effective forms of birth control include: 1. hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), 2. surgical sterility (tubal ligation or hysterectomy) 3. IUD 4. Diaphragm with spermicide 5. Condom with spermicide 9. For the methadone arm, use of any drugs that would interact with methadone to produce adverse effects such as Class I or Class III antiarrhythmics, TCA s, MAOI s, calcium channel blockers, neuroleptics or frequent use of sedative hypnotic drugs. Justification: Avoidance of adverse interaction with methadone. Assessment tool(s): Clinical interview and tox screen. 10. Use of any drugs (prostaglandins, vasoconstricting agents or anesthetic medications, for example) that may interact with oxytocin. Justification: Avoidance of adverse interaction with oxytocin. Assessment tool(s): Clinical interview and tox screen 11. History of hypersensitivity to oxytocin or vehicle, i.e. propylparahydroxybenzioate, methylparahydroxybenziate, chlorbutanol hemihydrate. Assessment tool: clinical interview 12. Presence of or history of clinically significant allergic rhinitis as assessed by MRP or PI. Justification: Inflammation of nasal mucosa could interfere with mucosal absorption of intranasally administered OT. In addition, participants will be excluded from fMRI scanning if they: 13. Are not suitable for fMRI due to pregnancy, implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is the primary measurement tool used in this portion of the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Pregnancy tests will be performed on all female participants of childbearing age before each experimental session. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their screening visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to physically fit into the scanner. 14. Have coagulopathies, history of or current superficial or deep vein thrombosis, or musculoskeletal abnormalities restricting ability to lie flat for extended periods. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) or dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues. 15. Have HIV or syphilis. Justification: HIV and syphilis can both have CNS sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): HIV blood test, syphilis serology (positive FTA). 16. Have any neurological illnesses. This includes, but is not limited to, seizure disorders, migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, or CNS tumor. Justification: CNS diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the BOLD fMRI signal to be used in this study. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 5 minutes or with postconcussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary. 17. Regularly use any prescription, over-the-counter, or herbal medication that may alter CNS function, cardiovascular function, or neuronal-vascular coupling. Justification: Compounds that alter BOLD signal will alter the primary measure used in the study. Assessment tool(s): History and comprehensive urine drug screening to detect use of antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates, and other common medications and drugs of abuse. All participants who are fullfill criteria for fMRI scanning will be asked to undergo scanning; we anticipate that approximately 50 percent of enrolled participants will be scanned.