Tolcapone Treatment of Pathological Gambling

Inclusion Criteria: 1. Men and women age 21-75; 2. Meet diagnostic criteria for current pathological gambling based on DSM-IV criteria and confirmed using the clinician-administered Structured Clinical Interview for Pathological Gambling (SCI-PG) (Grant et al., 2004); 3. Gambling behavior within 2 weeks prior to enrollment; 4. Women of child bearing age are required to have a negative result on a beta-human chorionic gonadotropin pregnancy test; 5. Women of childbearing potential utilizing a medically accepted form of contraception defined as double barrier, oral contraceptive, injectable contraceptive, implantable contraceptive devices, and abstinence. Exclusion Criteria: 1. Infrequent gambling (i.e. less than one time per week) that does not meet DSM-IV criteria for PG; 2. Unstable medical illness or clinically significant abnormalities on laboratory tests, EKG, or physical examination at screen as determined by the investigator; 3. History of elevated liver enzymes (AST/ALT) or other liver abnormalities; 4. History of seizures; 5. Myocardial infarction within 6 months; 6. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential; 7. A need for medication other than tolcapone with possible psychotropic effects or unfavorable interactions as determined by the investigator; 8. Clinically significant suicidality (defined as score 2 or higher on HAM-D item 3); 9. Current co-morbid Axis I disorder determined by the Structured Clinical Interview for DSM-IV (SCID), (First et al., 1995) - except for nicotine dependence; 10. Lifetime history of bipolar disorder type I or II, schizophrenia, or any psychotic disorder determined by SCID; 11. Clinically significant cognitive impairment (defined as score less than 88 on 3MS); 12. Current or recent (past 3 months) DSM-IV substance abuse or dependence; 13. Positive urine drug screen at screening; 14. Initiation of psychotherapy or behavior therapy for pathological gambling within 3 months prior to study baseline; 15. Previous treatment with tolcapone; 16. Treatment with an investigational medication or depot neuroleptics within 3 months; 17. Refusal to sign the tolcapone information sheet.