The Effect of Glutamatergic Modulation on Cocaine Self-administration

Inclusion Criteria: 1. Active cocaine dependence with at least 8 days of use or at least 4 binges of large amounts (\>$200/occasion) over the past 30 days, and displaying at least one positive utox during screening 2. Physically healthy 3. No adverse reactions to study medications 4. 21-55 years of age 5. Capacity to consent and comply with study procedures, including sufficient proficiency in English 6. Not seeking treatment Exclusion Criteria: 1. Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance induced psychosis, and current substance-induced mood disorder with HAMD score \> 12. 2. Physiological dependence on another substance, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis 3. Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders 4. Current suicide risk or a history of suicide attempt within the past year 5. Pregnant or interested in becoming pregnant during the study period 6. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse 7. Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (\>140/90), WBC \< 3.5, active hepatitis or other liver disease with elevated transaminase levels (\< 2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creat \> 2, BUN \>40), or untreated diabetes 8. Previous history of ketamine or midazolam misuse or abuse, and a history of an adverse reaction/experience with prior exposure to cocaine, ketamine or midazolam 9. Recent history of significant violence (past 2 years) 10. Abnormal pseudocholinesterase level 11. First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS) 12. BMI \> 35, or a history of documented obstructive sleep apnea 13. On psychotropic or other medications whose effect could be disrupted by participation in the study