For the subjective responses, both 0.5 and 1.0 mg nicotine/70 kg, compared to saline, increased the ratings of the “stimulatory” (main effect for dose: F(2,2643)=123.5; P<0.0001) and “feel good” (main effect for dose: F(2,2644)=124.6; P<0.0001) domains but not the “negative” domain (main effect for dose: F(2,2644)=0.31; P>0.05). The 1.0 mg nicotine/70 kg dose also increased subjective responses relative to the 0.5 mg nicotine/70 kg dose for ratings of “stimulatory” (main effect for dose: F(1,1811)=9.4; P<0.005) and “feel good” (main effect for dose: F(1,1810)=6.6; P<0.05) effects but not “negative” effects. Smokers who were C- carriers reported lower levels of “negative” effects than A-homozygotes in response to saline administration (main effect for group: F(1,192)=5.2; P<0.05 and group-by-dose interaction: F (2, 2640)=8.52; P<0.0005) (Figure 2A). There was a modest genotype-by-dose interactive effect on reports of “feel good” effects (group-by-time interaction; F(1,192)=4.0; P<0.05), with no significant group differences for the saline or nicotine doses (Supplementary Figure S2).
