Glutamatergic Modulation of Motivation Enhancement: A Pilot Feasibility Trial

Inclusion Criterion Method of Ascertainment

• 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 SCID, Psychiatric Interview, self-report, utox
• Physically healthy Laboratory tests (urinalysis, blood chemistry, 12-lead ECG in normal limits), physical examination, self-reported medical history
• No adverse reactions to study medications Subjects will be asked about previous exposure to ketamine and midazolam
• 21-55 years of age Self-reported age, verification with legal identification
• Capacity to consent and comply with study procedures, including sufficient proficiency in English A short written test about study procedures, SCID, psychiatric interview
• Seeking treatment Psychiatric Interview, self-report

Exclusion Criterion Method of Ascertainment

• 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. Psychiatric Interview, SCID, HAMD
• Physiological dependence on another substance, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis SCID, Psychiatric Interview
• Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders SCID, Psychiatric Interview
• Current suicide risk or a history of suicide attempt within the past year SCID, Psychiatric Interview
• Pregnant or interested in becoming pregnant during the study period Blood and urine pregnancy testing, self-report
• Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse Laboratory tests (12-lead ECG in normal limits), physical examination, self-reported medical history
• 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 Physiological tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, self-reported medical history
• 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 Physical examination, self-reported medical history
• Recent history of significant violence (past 2 years) SCID, Psychiatric Interview
• Abnormal pseudocholinesterase level Blood testing
• First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS) SCID, Psychiatric Interview
• BMI > 35, or a history of documented obstructive sleep apnea Physical examination, self-reported medical history
• On psychotropic or other medications whose effect could be disrupted by participation in the study Psychiatric interview, self-reported medical history
• Patients who cannot comply with study procedures during the initial hospitalization phase Study Performance