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Developing and validating a human laboratory model to screen medications for smoking cessation.

Sherry A McKee1, Andrea H Weinberger, Julia Shi

  • 1Department of Psychiatry, Yale University School of Medicine, 2 Church Street South, Suite 109, New Haven, CT 06519, USA. sherry.mckee@yale.edu

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
|April 12, 2012
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Summary

A new human laboratory model of smoking lapse behavior effectively screens smoking cessation medications. This model, sensitive to nicotine deprivation and medication effects, shows promise for developing new treatments for nicotine dependence.

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Area of Science:

  • Behavioral Science
  • Pharmacology
  • Addiction Medicine

Background:

  • Developing effective smoking cessation medications requires reliable translational research tools.
  • A human laboratory model simulating smoking lapse behavior is needed to bridge preclinical and clinical studies.
  • This model captures key aspects of lapse, including resistance to the first cigarette and subsequent smoking.

Purpose of the Study:

  • To develop and validate a human laboratory model of smoking lapse behavior.
  • To assess the impact of nicotine deprivation and monetary reinforcement on smoking lapse.
  • To evaluate the model's sensitivity to known smoking cessation medications.

Main Methods:

  • Study 1: Developed model parameters using varying nicotine deprivation (1-18 hours) and monetary reinforcement levels.
  • Study 2: Validated the model by randomizing subjects (n=62) to varenicline, bupropion, or placebo.
  • Assessed ability to resist smoking and subsequent ad libitum smoking, with craving, mood, and withdrawal as secondary outcomes.

Main Results:

  • Increased nicotine deprivation and decreased monetary reinforcement reduced smoking resistance in Study 1.
  • The lapse model detected medication effects in heavy, automated smokers in Study 2.
  • Secondary outcome measures (craving, mood, withdrawal) aligned with clinical findings.

Conclusions:

  • The developed smoking lapse model shows potential as a translational tool for screening novel smoking cessation medications.
  • The model's sensitivity to medication effects in specific smoker phenotypes was demonstrated.
  • Future research will focus on evaluating the predictive validity of this smoking lapse model.