For tolerance, we considered age of initiation of daily smoking, as it is shown to predict earlier age at heaviest smoking (Kendler et al. 2013). Further, we considered CPD, max CPD ever smoked during a 24 h period, and CPD at the period of heaviest smoking, as smoking quantity may affect the development of tolerance; rodent studies show that rapid tolerance is related to frequency of nicotine administration and dose (Aceto et al. 1986).
