Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence

SPECIFIC AIMS

• 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.
• 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.
• 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.
• . 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.
• 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 Carbon monoxide.

To achieve these aims, we will conduct a double-blind, randomized, placebo-controlled trial in a convenience sample of 50 smokers.

Inclusion:

• Healthy smokers aged 18-65 who have smoked at least 10 cigarettes/day for the past 3 months

Exclusion:

• Age <18 or >65
• Systolic blood pressure <100 mm Hg;
• Medical condition that contraindicates the administration of propranolol, e.g., history of congestive heart failure, heart block, insulin-dependent diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criterion may be overly restrictive. Therefore, asthma attacks will only be exclusionary if they a.) occurred within the past ten years, b.) occurred at any time in life if induced by a B-blocker, or c.) are currently being treated, regardless of the date of last occurrence. Cardiological consultation will be obtained as necessary;
• Previous adverse reaction to, or non-compliance with, a B-blocker;
• Current use of medication that may involve potentially dangerous interactions with propranolol, including, other B-blockers, antiarrhythmics, or calcium channel blockers.
• Use of drugs of abuse other than nicotine or caffeine, such as opiates, marijuana, cocaine, or amphetamines, as determined by saliva or urine testing;
• Pregnancy (in women of child-bearing potential, a pregnancy test will be performed) or breast-feeding;
• Current PTSD, or psychotic, melancholic, or bipolar disorder
• Diagnosis of major depressive disorder in the past 6 months or HAM-D score >15 at screening
• Current participation in any additional nicotine dependence treatment.
• An urgent need to stop smoking: subjects who receive placebo may not achieve optimal smoking cessation results.
• Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation;
• Subject candidate does not understand English