Neural Substrates of Emotion: Impact of Cocaine Dependence
Condition: Cocaine Use Disorder
MeSH terms: Cocaine-Related Disorders
Intervention: Oxytocin; Placebo
Intervention description: Nasal spray based on naturally occurring hormone, oxytocin.
Intervention MeSH terms: Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 138.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Over one million individuals in the United States meet criteria for cocaine use disorders.
      Relapse rates are highest among cocaine-dependent (CD) populations. Social stress is a
      significant risk factor for relapse. Data from human neuroimaging studies suggest that
      "top-down" prefrontal cortical inhibition of amygdala activity controls emotional responses
      to social stimuli. A growing literature suggests that hypoactivity in the medial prefrontal
      cortex coupled with increases in amygdala activity underscore the vulnerability of CD
      individuals to relapse. Neuroimaging studies of corticolimbic network activity (functional
      connectivity) have been conducted in CD subjects at rest. Compared with healthy controls, CD
      subjects exhibited lower corticolimbic connectivity and the degree of corticolimbic
      uncoupling was associated with time to relapse. Studies measuring corticolimbic connectivity
      during exposure to a social stress task in CD subjects could provide critical insight into
      the neurobiologic mechanisms that underscore the sensitivity of CD individuals to social
      stress. Moreover interventions that improve corticolimbic connectivity in CD subjects may be
      effective therapeutic strategies for preventing relapse in CD populations. Oxytocin (OT) is
      an anxiolytic neuropeptide that attenuates amygdala responses to aversive social cues. In
      order to better understand the neurobiologic mechanisms that control emotion-related behavior
      in CD populations, we propose a double-blind placebo (PBO) controlled study using blood
      oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure (1)
      corticolimbic functional connectivity during the Montreal Imaging Stress Task (MIST) and (2)
      amygdala activity in response to an implicit facial affect recognition paradigm in groups of
      CD individuals (CD n=80) and healthy non-dependent controls (HC, n=80). Prior to the scanning
      session, participants will receive either intranasal OT (24 IU) or PBO spray (n=40 per
      treatment group). The order of the tasks will be counterbalanced.
    

Eligibility criteria:

        General Inclusion/Exclusion Criteria Inclusion Criteria

          1. Age 18-65.

          2. Subjects must be able to provide informed consent and function at an intellectual
             level sufficient to allow accurate completion of all assessment instruments.

          3. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine)
             for the three-day period immediately prior to the study visit.

          4. Subjects must consent to random assignment.

          5. Subjects must have a negative breathalyzer, urine drug screen at the study visit.

          6. Subjects must consent to the study visit which includes an outpatient visit to the ASD
             and completing one functional magnetic resonance imaging (fMRI) scanning session.

        Exclusion Criteria

          1. Subjects with evidence of or a history of significant hematological, endocrine,
             cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including
             diabetes.

          2. Subjects with a history of or current psychotic disorder or bipolar affective
             disorder.

          3. Subjects with current major depressive disorder or post-traumatic stress disorder.

          4. Subjects taking any psychotropic medications, including SSRI's or other
             antidepressants, opiates or opiate antagonists. Subjects taking trazodone or
             non-benzodiazepene hypnotics for sleep will be included.

          5. Women who are pregnant, nursing or of childbearing potential and not practicing an
             effective means of birth control.

          6. Subjects who have a BMI that procludes them from fitting comfortably in the scanner.

          7. Persons with ferrous metal implants or pacemaker.

          8. Subjects that are claustrophobic.

          9. Subjects with significant psychiatric or medical problems that would impair
             participation or limit ability to complete the scanning session.

         10. Subjects that require maintenance or acute treatment with any psychoactive medication
             including anti-seizure medications which could potentially interfere with fMRI data
             acquisition.

        Group - Specific Inclusion/Exclusion Criteria Individuals with Cocaine Dependence Inclusion
        Criteria

        1. Subjects must meet DSM-5 criteria for current (three months prior to study visit)
        moderate to severe cocaine use disorder. Individuals may meet criteria for mild marijuana
        use disorder, but they must not meet criteria for substance use disorder for any other
        substance (except nicotine) within the 60 days prior to study participation. Due to the
        high comorbidity of alcohol and cocaine use disorder individuals with alcohol use disorder
        will be included in the study if they do not require medically supervised detoxification.

        Exclusion Criteria 1. Subjects meeting DSM-5 criteria for substance use disorder (other
        than nicotine, cocaine, marijuana or alcohol) within the 60 days prior to study
        participation.

        Healthy Controls Inclusion Criteria

        1. As above. Exclusion Criteria

          1. Subjects meeting DSM-5 criteria for current or lifetime substance use disorder on any
             drugs of abuse (except nicotine and marijuana.

          2. Subjects meeting DSM-5 criteria for marijuana use disorder within the last year.

          3. Subjects with current major depression or post-traumatic stress disorder (past month)