Oxytocin and Cognitive Behavioral Therapy in Drug Dependence
Condition: Drug Dependence
MeSH terms: Substance-Related Disorders
Intervention: Cognitive Behavioral Therapy; Intranasal Oxytocin; Placebo
Intervention description: Intranasal oxytocin given in the context of cognitive behavioral therapy; Intranasal oxytocin given in the context of cognitive behavioral therapy; Placebo given in the context of cognitive behavioral therapy
Intervention MeSH terms: Oxytocin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug Dependence; Cognitive Behavior; Oxytocin; Cocaine; Heroin; fMRI

Summary:

      Background:

      - The therapeutic alliance between therapist and patient may contribute to favorable outcomes
      in all types of psychotherapy, including cognitive behavioral therapy (CBT) for drug
      dependence. Oxytocin, a hormone and neurotransmitter, has been shown to increase trust in
      other people and may reduce stress and improve comfort in social situations by decreasing the
      sensation of social anxiety. Researchers are interested in determining if oxytocin can
      improve the outcomes of therapy for drug dependence by strengthening perceived levels of
      trust between therapist and patient.

      Objectives:

      - To determine whether oxytocin enhances the therapeutic alliance and treatment retention for
      CBT for drug use.

      Eligibility:

      - Individuals between 18 and 65 years of age who are healthy volunteers with no history of
      drug abuse, participants in outpatient or inpatient treatment programs for cocaine use,
      methadone-dependent participants in a treatment program, or non-treatment-seeking cocaine
      users.

      Design:

        -  Participants in each treatment arm who comply with the study requirements will be
           randomly assigned to receive one dose of oxytocin or placebo approximately 1 hour before
           each weekly CBT session.

        -  The outpatient treatment intervention will be 12 weeks of weekly individual CBT. The
           inpatient treatment intervention will be 6 weeks of twice-weekly individual CBT
           sessions. Sessions will be audiotaped. Participants and counselors will be told that the
           sessions are to be taped.

        -  During treatment, participants will provide urine and breath samples under staff
           observation. Participants will also complete questionnaires about mood and mental
           health, provide other samples as required, and participate in computerized psychological
           testing as directed by researchers.
    

Eligibility criteria:

        -  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.