Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving

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).