Presentation of cues involved in prior learning can elicit retrieval of memory for the learning. Retrieved memories are unstable before they are reconsolidated back into long-term storage. While unstable, the memories can be altered such that behaviors previously supported by the memories are significantly altered or eradicated. Nicotine addiction is multi-determined but one major etiological factor in the initiation and maintenance of smoking behavior is memory for smoking-related learning that develops as a consequence of frequent pairings between cues (e.g., sight and smell of cigarettes) and nicotine reward. The craving and other reactions that are elicited by exposure to these conditioned cues represent a significant threat to sustained cessation. Cue exposure therapy, which involves the repeated presentation of smoking cues in the absence of nicotine reward, was developed to extinguish cue-elicited craving and reactivity. Enthusiasm for this therapy waned as research revealed that extinguished responses would often reemerge with passage of time or if a smoking lapse occurred. The proposed exploratory study developed out of a recent Science publication that reported on the effects of a novel retrieval-extinction intervention on craving an cue reactivity in detoxified heroin addicts. The retrieval-extinction intervention consisted of two sessions in which brief heroin cue presentations, designed to elicit retrieval, were followed closely in time by protracted heroin cue exposure. Remarkably, this brief intervention led to significant reductions in heroin craving and cue reactivity that were sustained for 6-months. One explanation for these finding is that the brief 'retrieval'cue exposure initiated reconsolidation, thereby opening a window of opportunity in which protracted cue exposure could update the memories with information that would lead to dampened responsiveness to heroin cues. Given these initial and impressive findings, we propose to examine the effects of two sessions of retrieval-extinction training in smokers who are making a quit attempt. Retrieval will be initiated by a brief (5-min.) video with smoking-related content and the extinction will consist of protracted (1 hr.) exposure to smoking cues. A control group receiving the same treatment except that the retrieval video will have nonsmoking/neutral content will serve to demonstrate that retrieval is a key feature of retrieval-extinction training. Effects of the training on smokin craving and cue reactivity will be assessed 1-day, 2-weeks and 4-weeks post-training. The effects of the training on indices of smoking will also be preliminarily assessed. It is expected that the smoking-cue retrieval feature of this training will result in significant and enduring reductions in craving and reactivity to smoking cues and have a favorable impact on smoking. Positive findings from this study could lead to a safe and effective behavioral intervention that will help smokers overcome the threat to cessation posed by cue-elicited craving and reactivity, and thereby reduce the burden levied against society by this most costly addiction. Additionally, this treatment could be modified to address addiction to other substances of abuse.

Public Health Relevance

Smoking is a prevalent and treatment resistant addictive behavior and it remains the single greatest substance-related public health problem. The proposed innovative research will attempt to demonstrate that the memory processes underlying smoking addiction may be altered, with a brief behavioral intervention, to achieve lasting reductions in craving and other reactions to smoking cues. The results of this investigation could lead to the development of brief therapy that will not only enhance treatment outcomes for smokers, but also be generalizable to other substance use disorders.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Risk, Prevention and Intervention for Addictions Study Section (RPIA)
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Grossman, Debra
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Medical University of South Carolina
Other Health Professions
Sch Allied Health Professions
United States
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Germeroth, Lisa J; Baker, Nathaniel L; Saladin, Michael E (2018) Intolerance for smoking abstinence among nicotine-deprived, treatment-seeking smokers. Addict Behav 84:13-19
Germeroth, Lisa J; Carpenter, Matthew J; Baker, Nathaniel L et al. (2017) Effect of a Brief Memory Updating Intervention on Smoking Behavior: A Randomized Clinical Trial. JAMA Psychiatry 74:214-223