Clinical Neurobiology of Serotonin and Addiction

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:

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

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