Glutamatergic Modulation of Cocaine-related Deficits
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: Ketamine 0.41 mg/kg; Ketamine 0.71 mg/kg; Lorazepam 2 mg
Intervention description: 52 minute iv infusion of ketamine 0.41 mg/kg; 52 minute iv infusion of ketamine 0.71 mg/kg. This dose follows K1 in all 3 orderings.; 52 minute infusion of lorazepam 2 mg. This serves as an active control.
Intervention MeSH terms: Ketamine; Lorazepam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 8.0
Sex: All
Minimum age: 21 Years
Maximum age: 52 Years
Healthy volunteers: No

Summary:

      Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to
      cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits.
      Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators,
      studies with human subjects have been unsuccessful to date. The purpose of this investigation
      is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent
      therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting
      cocaine in cocaine dependent participants, 24-hours post-infusion.
    

Eligibility criteria:

        Inclusion Criteria

          1. Active free-base cocaine dependence (at least 4 days of use over the past month, with
             at least 1 use per week); if the participant uses through another route (IN, IV), then
             the FB route is dominant (> 80% of occasions).

          2. Physically healthy

          3. No adverse reactions to study medications

          4. 21-52 years of age

          5. Normal body weight

          6. Responsive to drug cues

          7. Capacity to consent

        Exclusion Criteria:

          1. Seeking treatment or abstinence

          2. DSM IV criteria for substance dependence (other than methamphetamine, cocaine,
             cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam

          3. DSM-IV criteria for other Axis I psychiatric illness that may make participation
             hazardous such as schizophrenia, schizoaffective disorder, psychosis NOS, MDD,
             psychosis secondary to substances, or bipolar disorder

          4. Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders

          5. Current suicide risk or a history of suicide attempt within the past 2 years

          6. Current use of prescribed psychotropic medication

          7. Pregnancy, nursing, or had a baby within the past 6 mo.

          8. Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.

          9. Unstable physical disorders which might make participation hazardous such as end-stage
             AIDS, hypertension (>140/90), anemia, active hepatitis or other liver disease, or
             diabetes

         10. "Bad" reaction/experience with prior exposure to ketamine or lorazepam

         11. History of significant violence

         12. First degree relative with a psychotic disorder