Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence
| Status: | Archived |
|---|---|
| Conditions: | Smoking Cessation, Tobacco Consumers |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | April 2008 |
| End Date: | January 2011 |
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.
SPECIFIC AIMS
1. To evaluate, in current smokers, the efficacy of a single dose of study medication
given an hour prior to smoking-related cue exposure (post-reactivation treatment) on
psychophysiological response to smoking cues one week later.
2. To evaluate, during the smoking cessation process, the clinical effect of study
medication in an ensuing series of 6 post-reactivation treatments on psychophysiologic
response to smoking cues measured one week after the last post-reactivation treatment.
3. To evaluate whether medication effect on psychophysiologic response during a single
memory reactivation session with script-driven imagery will predict clinical response
to an ensuing series of 6 post-reactivation treatments with script-driven imagery and
study medication.
4. . To assess whether a single post-reactivation treatment or series of six
post-reactivation treatments is associated with reduction in self-reported craving for
cigarettes as assessed with the Tiffany QSU.
5. To assess whether a series of six post-reactivation treatments is associated with
reduction in smoking as assessed with self-report of cigarettes smoked per day and
expired air CO.
To achieve these aims, we will conduct a double-blind, randomized, placebo-controlled trial
in a convenience sample of 50 smokers.
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