Background~Relapse to drug abuse or addiction is thought to result, in many cases, from exposure to cues that elicit drug-related memories. The term memories is used here not in its everyday sense, but in a sense that corresponds more closely to emotional associations for example, the association between the sight of a crack pipe and a set of responses such as rapid heartbeat and desire for cocaine. Studies in rodents and humans show that this type of memory is reconsolidated (actively re-stored) each time it is reactivated, and that the reconsolidation process can be disrupted by propranolol. Such disruption does not erase the autobiographical memory of an event, but instead weakens the link between that memory and an emotional response. Human studies are needed to determine whether propranolol disrupts reconsolidation of drug-cued memories in addicted individuals; this would present a novel and exciting therapeutic possibility for preventing craving and relapse.~Objective~To examine whether administration of propranolol interferes with reconsolidation of cocaine-related memories and reduces cravings and drug use in substance abusers.~Study population~Up to 200 (60 evaluable) individuals maintained on methadone and using cocaine will be recruited from local treatment programs. The target enrollment will include 40% women and 60% minorities.~Experimental design and methods~Participants will be randomized to one of two groups: propranolol (40 mg, oral, immediate-release formulation) or placebo. The study will include four laboratory sessions: (1) An information-gathering session that includes an interview to obtain information for development of a personalized drug script/cue set. (2) A two-hour intervention session in which there will be baseline measures, drug administration (propranolol or placebo, double blind), and, starting 60 min after drug administration, two script-guided imagery sets. Cue-responsivity data will be collected, but the main purpose of the session is interventional. This will be the only administration of propranolol during the study. (3, 4) Two follow-up test sessions, 1 and 5 weeks after the intervention session; participants responses to re-exposure to the personalized drug script/cue set will be measured. In addition to attending the four laboratory sessions, participants will make brief visits to our outpatient clinic for twice-weekly monitoring of ongoing drug use via urine screens and self-report, starting 1 week before the intervention session and ending 5 weeks later.~Outcome measures~Outcome measures will include subjective ratings of drug craving, autonomic responses (heart rate, blood pressure, galvanic skin response), and cocaine and heroin use (urine drug screens and self-reported drug use).
Background:~Relapse to drug abuse is thought to result, in many cases, from exposure to cues that trigger drug-related memories or emotional associations for example, the association between the sight of a crack pipe and a set of responses such as rapid heartbeat and desire for cocaine. This type of memory is reconsolidated (actively re-stored) each time it is reactivated; however, the reconsolidation process can be disrupted by the drug propranolol, which weakens the link between that memory and an emotional response.~Propranolol is traditionally used to treat high blood pressure and other heart-related conditions. Researchers are interested in studying whether propranolol disrupts reconsolidation of drug-cued memories in individuals who are addicted to cocaine.~Objectives:~- To examine whether propranolol can interfere with reconsolidation of cocaine-related memories and reduce cravings and drug use in substance abusers.~Eligibility:~- Individuals between 18 and 55 years of age who are current cocaine users enrolled in a methadone treatment program.~Design:~The study will involve four long sessions (visits 1, 4, 6, and 14) and 10 short sessions. The short visits will be for monitoring of participants use of drugs and alcohol; the longer visits will involve more tests and lab sessions. Participants will be randomized to either the propranolol or placebo group.~The long sessions will involve the following procedures:~An interview session to develop a personalized drug script/cue set.~A two-hour intervention session with baseline measures, drug administration (propranolol or placebo), and two script-guided imagery sets. This is the only administration of propranolol during the study.~Two follow-up test sessions, 1 and 5 weeks after the intervention session.~Participants will make brief visits to our outpatient clinic for twice-weekly monitoring of ongoing drug use via urine screens and self-report, starting 1 week before the intervention session and ending 5 weeks later.