Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial.

This study examined the role of dopaminergic genes in prospective smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial. Smokers of European ancestry (N=418) provided blood samples for genetic analysis and received either bupropion or placebo (10 weeks) plus counseling. Assessments included the dopamine D2 receptor (DRD2) genotype, dopamine transporter (SLC6A3) genotype, demographic factors, and nicotine dependence. Smoking status was verified at the end of treatment (EOT) and at 6-month follow-up. The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT, independent of treatment condition. Such effects were no longer significant at 6-month follow-up, however. These results provide the first evidence from a prospective clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase.     

Representation and rationality

David Lewis (1974, 1994/1999) proposed to reduce the facts about mental representation to facts about sensory evidence, dispositions to act, and rationality. Recently, Robert Williams (2020) and Adam Pautz (2021) have taken up and developed Lewis's project in sophisticated and novel ways. In this paper, we aim to present, clarify, and ultimately object to the core thesis that they all build their own views around. The different sophisticated developments and defenses notwithstanding, we think the core thesis is vulnerable. We pose a dilemma by considering the two sides of a current epistemological controversy over the relation between evidence and rational belief: permissivism vs. uniqueness. As we argue, the prospects for the Lewisian project look dim when either supposition is clearly made.