Cocaine Dependence
Conditions
Keywords
cocaine, cocaine-dependent, propranolol, craving, beta-blockade, cue exposure, drug, addiction, memory, addictive behavior
Brief summary
The purpose of this study is to examine the effects of propranolol versus placebo on responses to cocaine cues in cocaine dependent individuals.
Detailed description
This study will employ cocaine-dependent individuals to investigate the acute effects of propranolol vs. placebo, administered immediately after a retrieval session of cocaine cue exposure, on the subjective and physiological responses occurring during a subsequent test session of cocaine cue exposure. Participants (N=52) will be randomly assigned to receive 40 mg propranolol or placebo immediately after the first of two cocaine cue exposure sessions scheduled to occur on consecutive days of an inpatient stay at MUSC's General Clinical Research Center (GCRC). The first session will serve as a retrieval session where cocaine cue exposure will putatively elicit retrieval and reconsolidation of memories about the association between the cues and cocaine administration; the second session of cocaine cue exposure will be a test session to examine the potential modulatory role of propranolol on the reconsolidated memories putatively elicited during the previous cue exposure session. It is assumed that changes in craving and physiological reactivity during the test session will reflect propranolol's effects on memory reconsolidation processes elicited by cue exposure during the retrieval session. Medications will be administered in a double-blind fashion. Craving and physiological arousal (heart rate, skin conductance, blood pressure) will be obtained at baseline and at regular intervals during and after both cue exposure sessions. Approximately 7 days following discharge from the inpatient stay at the GCRC, participants will return to the GCRC to undergo a 1-week follow-up cue exposure session that will be identical to the previous two sessions (no medications will be administered). The goal of the follow-up will be to examine if any craving and/or physiological reactivity differences identified during the test session were sustained and to assess if the groups differed in their cocaine use during the intervening 7-day period.
Interventions
DRUGPropranolol
40 mg administered once
DRUGPlacebo
administered once
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Current cocaine dependence (within past month) * Able to provide informed consent * Use of birth control by female participants (barrier methods, surgical sterilization, IUD, or abstinence) * Live within 50-mile radius of research site * Consent to remain abstinent from all drugs of abuse (except nicotine) for 24 hours prior to inpatient admission and follow-up assessment * Consent to random assignment to propranolol or placebo
Exclusion criteria
* Women who are pregnant, nursing or are of childbearing potential and not practicing/using birth control * Evidence or history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal or neurological disease * Significant liver impairment * History of or current psychotic disorder, current severe major depressive disorder, bipolar affective disorder or a severe anxiety disorder * Currently taking anti-arrhythmic agents, psychostimulants or other agents known to interfere with heart rate and skin conductance monitoring * Known or suspected hypersensitivity to propranolol * Individuals taking medications that could adversely interact with the study medication, including, but not limited to albuterol, insulin, or significant inhibitors of CYP2D6 * Individuals with bronchial asthma or chronic obstructive pulmonary disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single Item Craving Test Session Difference Scores | Both days of cue exposure | Mean of the difference of Session 1 and Session 2 cocaine craving scores (Session 2-Session 1). Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving. The difference score was found by subtracting session 1 mean SICs during cue exposure from session 2 mean SICs during cue exposure. Therefore the mean of the difference could have ranged anywhere from -100 to 100. Negative mean difference scores reflect a decrease in craving for cocaine from session 1 (test) to session 2 (retrieval). The lower the mean difference score, the greater the decrease in craving. |
Countries
United States
Participant flow
Recruitment details
Individuals who met DSM-IV criteria for current cocaine dependence (within the past month) but who were not dependent on any other substance, with the exception of nicotine, served as participants. The primary method of recruitment was media advertisement (radio, local papers) which ran from January of 2009 until July of 2011.
Pre-assignment details
Exclusion criteria included severe psychiatric comorbidity (e.g., psychotic disorder, bipolar disorder, severe major depressive disorder with suicidal ideation) or medical illness or use of medications that might interact with propranolol. Individuals with other substance dependence (with exception of nicotine) were also excluded at initial visit.
Participants by arm
| Arm | Count |
|---|---|
| Propranolol 40mg Propranolol : 40 mg administered once. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2). | 26 |
| Placebo Placebo : administered once. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2). | 24 |
| Total | 50 |
Baseline characteristics
| Characteristic | Propranolol 40mg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 39.1 years STANDARD_DEVIATION 1.6 | 40.8 years STANDARD_DEVIATION 2 | 39.9 years STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 0 / 24 |
| serious Total, serious adverse events | 0 / 27 | 0 / 24 |
Outcome results
Primary
Single Item Craving Test Session Difference Scores
Mean of the difference of Session 1 and Session 2 cocaine craving scores (Session 2-Session 1). Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving. The difference score was found by subtracting session 1 mean SICs during cue exposure from session 2 mean SICs during cue exposure. Therefore the mean of the difference could have ranged anywhere from -100 to 100. Negative mean difference scores reflect a decrease in craving for cocaine from session 1 (test) to session 2 (retrieval). The lower the mean difference score, the greater the decrease in craving.
Time frame: Both days of cue exposure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol 40mg | Single Item Craving Test Session Difference Scores | -25.0 units on a scale | Standard Error 4.5 |
| Placebo | Single Item Craving Test Session Difference Scores | -10.5 units on a scale | Standard Error 4.7 |