Effect of Nicotine on Brain Reward Pathways

Study Overview
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Brief Summary
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The investigators will determine whether an acute dose of nicotine, in the form of the nicotine lozenge, impacts brain and behavioral measures of mood and reward responsiveness in individuals with major depressive disorder.

Official Title
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Effect of Nicotine on Brain Reward Pathways

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: Nicotine polacrilex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for subjects with Major Depressive Disorder: Provide written informed consent; Both genders and all ethnic origins, age between 18 and 45; Meet DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID); A baseline HAM-D score of 16 or greater; Absence of pregnancy; Absence of any psychotropic medication for at least 2 weeks: 6 weeks for fluoxetine 6 months for neuroleptics 2 weeks for benzodiazepines 2 weeks for any other antidepressants Inclusion Criteria for Healthy Controls Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse); as assessed by subject history and a structured clinical interview (SCID); Provide written informed consent; Both genders and all ethnic origins, age between 18 and 45; Absence of any medications for at least 3 weeks; Absence of pregnancy. Exclusion Criteria: Subjects with suicidal ideation where outpatient treatment is determined unsafe. These patients will be immediately referred to a licensed psychologist or psychiatrist to determine the appropriate clinical treatment; Serious or unstable medical illness Lifetime history of seizure disorder; Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, ADHD, patients with mood congruent or mood incongruent psychotic features; simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD; Patients with a lifetime history of electroconvulsive therapy (ECT); Failure to meet standard MRI safety requirements; May not have used any nicotine product in the past year; must report fewer than 20 lifetime uses of nicotine Must have an expired carbon monoxide level of less than or equal to 10 ppm. Use of anticholinergic drugs in the past week Any past or present history of cardiac problems including known arrhythmias, acute coronary syndrome, or ischemic heart disease Uncontrolled hypertension History of substance abuse in the past 6 months (other than caffeine), self-reported use of marijuana in past month, or history of treatment with methadone Heavy caffeine users (consume greater than 500 mg on a regular or daily basis) Subjects that cannot speak English

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotine<br>2mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time. 4mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time. | Drug: Nicotine polacrilex<br>* Single Acute dose<br>* Other names: Nicotine lozenge;|
| Placebo Comparator: Placebo<br>Placebo comparator | Drug: Nicotine polacrilex<br>* Single Acute dose<br>* Other names: Nicotine lozenge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Placebo in functional magnetic resonance imaging (fMRI) BOLD Response | Nicotine will enhance the fMRI BOLD response to monetary reinforcers relative to placebo administration | Participants will be assessed during 2 fMRI scanning sessions, an expected average of 2 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine, Depression