Beta-blockade Effects on Memory for Cocaine Craving

The purpose of this study is to examine the effects of propranolol versus placebo on responses to cocaine cues in cocaine dependent individuals.

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.

cocaine, cocaine-dependent, propranolol, craving, beta-blockade, cue exposure, drug, addiction, memory, addictive behavior

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.

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