Nicotinic Receptors and Schizophrenia

Patients with schizophrenia will be screened then enrolled for one week placebo trial in addition to their existing antipsychotic medication. If pill compliance is greater than 80%, then they will receive baseline clinical, cognitive, and brain imaging and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram. Then patients will receive in a randomized double blind trial either DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) or placebo comparator in addition to their existing antipsychotic medication. After one month patients will receive repeat clinical, cognitive, and brain imaging testing and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram.

Inclusion criteria

• Subjects will be selected to be 18 to 65 years old and in good general health.
• Subjects who fulfill Diagnostic and Statistical Manual -IV-Text Revision (DSM-IV-TR) criteria for schizophrenia or schizoaffective disorder.
• Smokers will smoke at least 20 cigarettes per day.
• Non-smokers will also be enrolled.
• Subjects will have normal:

• vital signs,
• hematology,
• serum chemistries,
• EKG, and
• urinalysis with a negative drug screen before entry into the study.
• Subjects will be fluent in English.
• Smoking subjects will be interested in stopping smoking in the near future and not interested in nicotine replacement therapy.

Exclusion criteria

• Subjects with histories of:

• neurological illness,
• liver disease,
• severe hypertension (cut-off blood pressure 160/100) or
• cardiac disease, or
• renal failure (cut-off creatinine above 1.4).
• Subjects who currently meet DSM-IV-TR criteria for substance dependence other than nicotine, cannabis, or alcohol will be excluded.
• Women who are capable of pregnancy and not on acceptable forms of birth control will be excluded.
• Subjects being treated with Clozapine will be excluded.