The Effect of Glutamatergic Modulation on Cocaine Self-administration
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: CI-581a; CI-581b
Intervention description: a 50 minute infusion 24 hours prior to cocaine self-administration session; a 50 minute infusion 24 hours prior to cocaine self-administration session
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 18.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      Repeated drug consumption may progress to problematic use by triggering neuroplastic
      adaptations that attenuate sensitivity to natural rewards while increasing reactivity to
      craving and drug cues. Converging evidence suggests that glutamate modulation may work to
      correct these adaptations and rapidly restore motivation for delayed non-drug rewards
      relative to immediate drug use. Using an established laboratory model aimed at evaluating
      behavioral shifts in the salience of cocaine now vs. money later, the investigators will test
      the effect of CI-581a on cocaine self-administration as compared to the active control.
    

Eligibility criteria:

        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