Cocaine Dependence
Conditions
Brief 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.
Interventions
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Choices to Self-administer Cocaine (Out of 5 Choices) | 24 hours post-infusion | Participants provided 5 choices (cocaine 25 mg now vs. $11 later), with choices spaces 15 minutes apart over the course of the session. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CI-581a First, Followed by CI-581b Administration of CI-581a followed 2 weeks later by CI-581b
CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session
CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session | 10 |
| CI-581b First, Followed by CI-581a Administration of CI-581b followed 2 weeks later by CI-581a
CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session
CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | CI-581a First, Followed by CI-581b | Total | CI-581b First, Followed by CI-581a |
|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 6.1 | 48.6 years STANDARD_DEVIATION 6.1 | 48.6 years STANDARD_DEVIATION 6.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United States | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 0 / 10 | 0 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 |
Outcome results
Primary
Number of Choices to Self-administer Cocaine (Out of 5 Choices)
Participants provided 5 choices (cocaine 25 mg now vs. $11 later), with choices spaces 15 minutes apart over the course of the session.
Time frame: 24 hours post-infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CI-581a | Number of Choices to Self-administer Cocaine (Out of 5 Choices) | 1.61 number of cocaine choices | Standard Deviation 1.3 |
| CI-581b | Number of Choices to Self-administer Cocaine (Out of 5 Choices) | 4.33 number of cocaine choices | Standard Deviation 1.8 |