PK/PD Comparison of Guanfacine ER and IR

Inclusion Criteria: * Age 18-65 * Able to read, write and comprehend English * Smoker * Able to take oral medications and willing to adhere to medication regimen * Provide evidence of a stable living residence in the last 2 months, have reasonable transportation to the study site, and have no plans to move within the next 3 months or unresolved legal problems. Exclusion Criteria: * Any significant current medical conditions that would contraindicate smoking * Current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) abuse or dependence of other substances, other than nicotine dependence or alcohol abuse * Positive test results at intake appointment on urine drug screens for illicit drugs * Past 30 day use of psychoactive drugs including anxiolytics and antidepressants * Women who are pregnant or nursing * Suicidal, homicidal or evidence of current mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders * Meeting DSM-IV criteria for current attention deficit hyperactivity disorder (ADHD) * Individuals who are currently taking medications known to be effective for smoking cessation or are regular users of other tobacco products in the past 30 days * Only one member per household can participate in the study * Specific exclusions for administration of guanfacine not already specified include: * EKG evidence at baseline screening of any clinically significant conduction abnormalities or arrhythmias * Known intolerance for guanfacine or any alpha blocker * History of fainting, syncopal attacks * Heart failure or myocardial infarction * Impaired liver (as indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT) \>3x normal) * Renal function (as indicated by estimated creatinine clearance \<60cc/min) * Treatment with any antihypertensive drug or any alpha-adrenergic blocker * Use of any central nervous system depressant (e.g., phenothiazines, barbiturates, benzodiazepines) * Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin), or consumption of grapefruit juice * Subjects may have not donated blood in the past 8 weeks or have been involved in other investigational studies that involve substantial blood draws or medications unknown to us