Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving

Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving, Reactivity and Use

The investigators' recently completed study has provided the first evidence that administration of the medication propranolol, following exposure to cocaine cues, can alter drug-associated memories and reduce craving and other drug cue-elicited responses in cocaine addicted persons. The investigators will attempt to augment this effect by a) doubling the number of propranolol-medicated cocaine cue exposure (CCE) retrieval sessions and b) increasing the dose of propranolol. It is expected that propranolol treated groups, relative to placebo treated groups, will evidence greater reduction of craving, cue reactivity and cocaine use during follow-up cocaine cue exposures. Also, these effects will be greater for those who receive 80mg of propranolol as opposed to 40mg.

Three groups of CD (cocaine dependant) participants will receive two sessions of cocaine cue exposure (CCE), each separated by a 24 hr. period and both conducted while the participants remain in hospital. One group (PBO) will receive placebo following each CCE session while the second (40PP) and third (80PP) group will receive 40 mg and 80 mg propranolol, respectively. Participants will return two days, and 1, 3, and 6 weeks after discharge and will be administered a CCE session to assess for maintenance/generalization of disruption of reconsolidation (DoR) effects on craving and cue reactivity to familiar and novel cocaine cues. Participants will also be assessed 3 times weekly for cocaine use (self-report & urine drug screen) during follow-up.

Inclusion Criteria:

• Participants must meet DSM-IV criteria for current cocaine dependence (within the past month). Participants may meet criteria for abuse, but not dependence, for any other substance with the exception of nicotine. Because of the high comorbidity of cocaine and nicotine dependence, excluding nicotine dependence would seriously compromise the feasibility of recruitment (nicotine patch will be provided to participants during the course of their involvement in the laboratory procedures). Although individuals who meet criteria for alcohol abuse will be accepted for study participation, anyone who has a measurable blood alcohol level on the day of testing will be excluded as acute alcohol intake can lower seizure threshold.
• Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.Exclusion Criteria:
• Use of one of the following methods of birth control by female participants: barrier methods (diaphragm or condoms with spermicidal or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse.
• Individuals must live within a 50-mile radius of our research program and have reliable transportation.
• Individuals must consent to remain abstinent from all drugs of abuse (except nicotine) for 72 hours immediately prior to CTRC inpatient admission.
• Individuals must consent to random assignment to one of three study groups (the two propranolol-treated groups or the placebo-treated group).

Exclusion Criteria:

• Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
• Individuals with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect heart rate or skin conductance measurement.
• Individuals with significant liver impairment as propranolol is hepatically metabolized.
• Individuals with a history of or current psychotic disorder, current major depressive disorder, bipolar affective disorder or a severe anxiety disorder as these may impact cue reactivity.
• Individuals currently taking anti-arrythmic agents, psychostimulants or any 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, as the use of propranolol is contraindicated in these individuals.
• Individuals with any physical condition or disability that would compromise optimal sensory processing of the cues (e.g., blindness).