Cocaine Dependence
Conditions
Keywords
cocaine, modafinil, self-administration, DRD4
Brief summary
Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment seeking cocaine-dependent individuals (n = 8).
Interventions
DRUGModafinil 0 mg
Modafinil (0 mg/day)
DRUGModafinil 200 mg
Modafinil (200 mg/day)
DRUGModafinil 400 mg
Modafinil (400 mg/day)
DRUGCocaine 0 mg
Cocaine (0 mg/day)
DRUGCocaine 12 mg
Cocaine (12 mg/day)
DRUGCocaine 25 mg
Cocaine (25 mg/day)
DRUGCocaine 50 mg
Cocaine (50 mg/day)
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Smokes cocaine 2. Has patterns of smoked cocaine use in terms of frequency and amount which parallel or exceed those administered in the study. 3. Age 21-50. 4. Able to give informed consent, and comply with study procedures. 5. Normal body weight Within normal weight range (for appropriate frame) according to 1983 Metropolitan Weight tables -
Exclusion criteria
1. Current seizure disorder, heart disease or a history of serious adverse effects due to cocaine. 2. Dependence on substances (other than cocaine or nicotine) or a history of dependence on alcohol 3. Request for drug treatment 4. Judged to be noncompliant with study protocol. 5. Current use of any psychotropic medication. 6. Clinical laboratory tests outside normal limits that are clinically unacceptable to the study physician (BP \> 140/90; BUN, creatinine, LFTs \> 3x ULN; hematocrit \< 34 for women, \< 36 for men; pseudocholinesterase deficiency) 7. History of myocardial infarction or ischemia, clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse 8. Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders other than transient psychosis due to drug abuse 9. Current parole or probation Self-report during interview -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Self-administration | 48 days | The number of purchased cocaine doses as a function of cocaine dose and modafinil maintenance condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drug Quality Cluster | 48 days | Visual analogue scale ratings on the 'Drug Quality' cluster as a function of cocaine dose and modafinil maintenance condition. A cluster score was derived by taking the arithmetic average of the items in the cluster. Scores range from 0-100, with higher scores indicating greater agreement with the term. The Drug Quality Cluster consisted of three items: 1. the choice was of high quality 2. the choice was potent 3. I liked the choice Higher scores indicate increasing agreement with the statement, which would indicate a poorer outcome. |
| Heart Rate | 48 days | Values for heart rate as a function of cocaine dose and modafinil maintenance condition. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Modafinil + Cocaine During this within-subjects, alternating in-patient/outpatient 48-day study, participants were maintained on modafinil (placebo, 200, and 400mg/day) and four doses of smoked cocaine (0, 12, 25, and 50mg). | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | abnormal ECG before meds | 1 |
| Overall Study | Arrested | 1 |
| Overall Study | rash while on placebo | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Modafinil + Cocaine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 38.5 years STANDARD_DEVIATION 2.8 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Cocaine Self-administration
The number of purchased cocaine doses as a function of cocaine dose and modafinil maintenance condition.
Time frame: 48 days
Population: Eight patients contributed to each condition, in a within-subjects manner.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil 0mg + Cocaine 0mg | Cocaine Self-administration | 0 Number of doses purchased | Standard Error 0 |
| Modafinil 200mg + Cocaine 0mg | Cocaine Self-administration | 0 Number of doses purchased | Standard Error 0 |
| Modafinil 400mg + Cocaine 0mg | Cocaine Self-administration | 0 Number of doses purchased | Standard Error 0 |
| Modafinil 0mg + Cocaine 12mg | Cocaine Self-administration | 2.2 Number of doses purchased | Standard Error 0.3 |
| Modafinil 200mg + Cocaine 12mg | Cocaine Self-administration | 1.5 Number of doses purchased | Standard Error 0.3 |
| Modafinil 400mg + Cocaine 12mg | Cocaine Self-administration | 2.1 Number of doses purchased | Standard Error 0.1 |
| Modafinil 0mg + Cocaine 25mg | Cocaine Self-administration | 4.1 Number of doses purchased | Standard Error 0.2 |
| Modafinil 200mg + Cocaine 25mg | Cocaine Self-administration | 2.5 Number of doses purchased | Standard Error 0.3 |
| Modafinil 400mg + Cocaine 25mg | Cocaine Self-administration | 2.6 Number of doses purchased | Standard Error 0.3 |
| Modafinil 0mg + Cocaine 50mg | Cocaine Self-administration | 4.5 Number of doses purchased | Standard Error 0.1 |
| Modafinil 200mg + Cocaine 50mg | Cocaine Self-administration | 3.5 Number of doses purchased | Standard Error 0.3 |
| Modafinil 400mg + Cocaine 50mg | Cocaine Self-administration | 3 Number of doses purchased | Standard Error 0.3 |
Secondary
Drug Quality Cluster
Visual analogue scale ratings on the 'Drug Quality' cluster as a function of cocaine dose and modafinil maintenance condition. A cluster score was derived by taking the arithmetic average of the items in the cluster. Scores range from 0-100, with higher scores indicating greater agreement with the term. The Drug Quality Cluster consisted of three items: 1. the choice was of high quality 2. the choice was potent 3. I liked the choice Higher scores indicate increasing agreement with the statement, which would indicate a poorer outcome.
Time frame: 48 days
Population: Eight subjects participants in each condition in a within-subjects fashion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil 0mg + Cocaine 0mg | Drug Quality Cluster | 2 units on a scale | Standard Error 0.5 |
| Modafinil 200mg + Cocaine 0mg | Drug Quality Cluster | 2 units on a scale | Standard Error 0.5 |
| Modafinil 400mg + Cocaine 0mg | Drug Quality Cluster | 2 units on a scale | Standard Error 0.5 |
| Modafinil 0mg + Cocaine 12mg | Drug Quality Cluster | 30 units on a scale | Standard Error 5 |
| Modafinil 200mg + Cocaine 12mg | Drug Quality Cluster | 28 units on a scale | Standard Error 4 |
| Modafinil 400mg + Cocaine 12mg | Drug Quality Cluster | 29 units on a scale | Standard Error 3 |
| Modafinil 0mg + Cocaine 25mg | Drug Quality Cluster | 44 units on a scale | Standard Error 4 |
| Modafinil 200mg + Cocaine 25mg | Drug Quality Cluster | 35 units on a scale | Standard Error 4 |
| Modafinil 400mg + Cocaine 25mg | Drug Quality Cluster | 35 units on a scale | Standard Error 2 |
| Modafinil 0mg + Cocaine 50mg | Drug Quality Cluster | 60 units on a scale | Standard Error 3 |
| Modafinil 200mg + Cocaine 50mg | Drug Quality Cluster | 55 units on a scale | Standard Error 4 |
| Modafinil 400mg + Cocaine 50mg | Drug Quality Cluster | 55 units on a scale | Standard Error 4 |
Secondary
Heart Rate
Values for heart rate as a function of cocaine dose and modafinil maintenance condition.
Time frame: 48 days
Population: Eight patients participated in each condition in a within-subjects fashion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modafinil 0mg + Cocaine 0mg | Heart Rate | 88 BPM | Standard Error 2 |
| Modafinil 200mg + Cocaine 0mg | Heart Rate | 86 BPM | Standard Error 2 |
| Modafinil 400mg + Cocaine 0mg | Heart Rate | 91 BPM | Standard Error 2 |
| Modafinil 0mg + Cocaine 12mg | Heart Rate | 102 BPM | Standard Error 3 |
| Modafinil 200mg + Cocaine 12mg | Heart Rate | 101 BPM | Standard Error 2.5 |
| Modafinil 400mg + Cocaine 12mg | Heart Rate | 97 BPM | Standard Error 3 |
| Modafinil 0mg + Cocaine 25mg | Heart Rate | 130.5 BPM | Standard Error 2 |
| Modafinil 200mg + Cocaine 25mg | Heart Rate | 110 BPM | Standard Error 3 |
| Modafinil 400mg + Cocaine 25mg | Heart Rate | 115 BPM | Standard Error 2.5 |
| Modafinil 0mg + Cocaine 50mg | Heart Rate | 141 BPM | Standard Error 2 |
| Modafinil 200mg + Cocaine 50mg | Heart Rate | 125 BPM | Standard Error 4 |
| Modafinil 400mg + Cocaine 50mg | Heart Rate | 122 BPM | Standard Error 2 |