Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide.
Advancing new smoking cessation therapies, including those targeting novel biological
mechanisms, is a critical public health priority. Accumulating evidence from preclinical
studies suggests that glucagon-like peptide-1 (GLP-1) receptor agonists reduce intake and/or
reinstatement of addictive drugs, including nicotine. However, translational work is
necessary to establish whether GLP-1 receptor agonists alter aspects of nicotine response and
smoking behavior in smokers. Human laboratory studies play a pivotal role in drug development
by providing a time- and cost-efficient means of validating preclinical findings, also
providing an ideal platform for studying mechanisms of medication effects. This is an
experimental investigation to examine the effects of an approved GLP-1 receptor agonist on
nicotine intake and reinstatement. Dependent smokers will be enrolled in a double-blind,
parallel-arm trial with laboratory endpoints. Laboratory procedures will include a validated
procedure for measuring smoking lapse/reinstatement after overnight abstinence. This study
will provide initial laboratory evidence for the potential efficacy of GLP-1 receptor
agonists as adjunctive treatments for smoking cessation.