Clinical Neurobiology of Serotonin and Addiction

Project 1: Clinical Neurobiology of Serotonin and Addiction

The purpose of this study is to examine the relationship between 5-HT2R function, impulsivity and cue reactivity in cocaine dependent subjects and healthy controls and examine specific effects of escitalopram and mirtazapine on impulsivity and cue reactivity in human cocaine users.

Specific Aim 1: We will test the hypothesis that cocaine-dependent subjects will exhibit greater impulsivity than controls as determined by a battery of impulsivity measures and that impulsivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce impulsivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression.

Specific Aim 2: We will test the hypothesis that cocaine-dependent subjects will exhibit greater cue reactivity than controls as determined by a modified Stroop task, and that cue reactivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce cue reactivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression.

Specific Aim 3: We will test the hypothesis that specific polymorphisms in the 5-HT2AR and/or 5-HT2CR will predict baseline impulsivity and/or cue reactivity as well as treatment response to serotonergic medications in cocaine-dependent subjects.

Inclusion Criteria:

• Non-Drug Abusing Control Subjects: Male and female subjects age 18 to 55 who do not meet current or past DSM-IV criteria for any Axis I disorder including substance abuse or dependence.
• Cocaine Dependent Subjects: Male and female subjects age 18 to 55 who meet current DSM-IV criteria for cocaine dependence.
• Female subjects: a negative pregnancy test.

Exclusion Criteria:

• Non-Drug Abusing Control Subjects:

  1. Current or past DSM-IV Axis I disorder
  2. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system.
  3. Positive HIV test.
  4. For female subjects: a positive pregnancy test or breast feeding.
  5. Concomitant use of prescription medications that could affect the central nervous system.
  6. Active suicidal ideation.
  7. Hamilton Depression or Anxiety Scale score greater than 15

• Cocaine Dependent Subjects:

  1. Current DSM-IV Axis I disorder other than substance abuse/dependence
  2. Current diagnosis of other substance dependence besides cocaine.
  3. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system.
  4. Positive HIV test.
  5. For female subjects: a positive pregnancy test or breast feeding.
  6. Concomitant use of prescription medications that could affect the central nervous system.
  7. Active suicidal ideation.
  8. Subjects within 14 days of discontinuing a monoamine oxidase inhibitor.
  9. Subjects with cardiac arrythmias.
  10. Subjects with known hypersensitivity to escitalopram or citalopram, or mirtazapine
  11. Hamilton Depression or Anxiety Scale score greater than 15.
  12. Current alcohol abuse or dependence.