Glutamatergic Modulation of Motivation Enhancement: A Pilot Feasibility Trial

Inclusion Criterion Method of Ascertainment

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 SCID, Psychiatric Interview, self-report, utox

2. Physically healthy Laboratory tests (urinalysis, blood chemistry, 12-lead ECG in
normal limits), physical examination, self-reported medical history

3. No adverse reactions to study medications Subjects will be asked about previous
exposure to ketamine and midazolam

4. 21-55 years of age Self-reported age, verification with legal identification

5. Capacity to consent and comply with study procedures, including sufficient proficiency
in English A short written test about study procedures, SCID, psychiatric interview

6. Seeking treatment Psychiatric Interview, self-report

Exclusion Criterion Method of Ascertainment

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. Psychiatric Interview, SCID,
HAMD

2. Physiological dependence on another substance, such as alcohol, opioids, or
benzodiazepines, excluding caffeine, nicotine, and cannabis SCID, Psychiatric
Interview

3. Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders SCID,
Psychiatric Interview

4. Current suicide risk or a history of suicide attempt within the past year SCID,
Psychiatric Interview

5. Pregnant or interested in becoming pregnant during the study period Blood and urine
pregnancy testing, self-report

6. 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

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 Physiological tests (urinalysis, blood chemistry, 12-lead ECG), physical
examination, self-reported medical history

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 Physical
examination, self-reported medical history

9. Recent history of significant violence (past 2 years) SCID, Psychiatric Interview

10. Abnormal pseudocholinesterase level Blood testing

11. First degree relative with a psychotic disorder (bipolar disorder, schizophrenia,
schizoaffective disorder, or psychosis NOS) SCID, Psychiatric Interview

12. BMI > 35, or a history of documented obstructive sleep apnea Physical examination,
self-reported medical history

13. On psychotropic or other medications whose effect could be disrupted by participation
in the study Psychiatric interview, self-reported medical history

14. Patients who cannot comply with study procedures during the initial hospitalization
phase Study Performance