Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence
Status:
Completed
Trial end date:
2011-01-01
Target enrollment:
Participant gender:
Summary
Smoking is the leading cause of preventable morbidity and mortality in the US. While
approximately 70% of smokers attempt to quit each year, only 5-15% maintain abstinence for 12
months, even with effective pharmacological and psychological interventions. Novel therapies
are needed for smoking cessation and relapse prevention. Previous studies show that early
post-cessation craving or urge to smoke is a powerful predictor of relapse. A current model
of the pathogenesis of addiction maintains that a substance of abuse causes a marked increase
release in phasic dopamine release, which in turn strengthens or increases the salience of
the memory of the drug experience, leading to a powerful and persistent memory that is easily
activated, leading to drug craving and often to drug use. This highly salient memory is also
implicated in the physiological arousal associated with craving responses to smoking cues.
This process is thought to be implicated in relapse to drug use after even long periods of
abstinence. Recent animal research indicates that retrieval returns a consolidated memory
such as those associated with drug craving, to a labile state from which it must be
restabilized to persist in a process termed reconsolidation. If memories of drug-related
experiences are labile when reactivated, this could represent a window of opportunity in
which the memory of drug use that underlies drug craving can be influenced pharmacologically.
Our hypothesis is that post-reactivation administration of the B-adrenergic blocker,
propranolol, following retrieval of drug-associated memories will reduce the strength or
salience of the memory by influencing reconsolidation, a process called memory
reconsolidation blockade. In this study we will test the hypothesis that a single dose of
propranolol given one hour prior to smoking-related cue exposure (post-reactivation
treatment) will decrease psychophysiological responses to smoking cues one week later and
will predict clinical response to an ensuing series of 6 post-reactivation treatments with
script-driven imagery and propranolol. In order to do so, we propose to conduct a randomized,
double-blind, placebo-controlled trial of post-reactivation treatment with propranolol in 50
adult smokers. Outcome measures will include in physiological responses to smoking-related
cues after one and six post-reactivation treatments and smoking behavior during the treatment
and during a 3-month follow-up period.