“…Here, recent evidence indicates that people differ in their ability to metabolize opioids [52,53]. Smokers probably because of enzyme induction by nicotine have been reported to have less pain efficacy from propoxyphene [54], demonstrate increased metabolic clearance of pentazocine [55], require high doses of pentazocine [56], and have significantly lower levels of hydrocodone [31] vs nonsmokers. Thus, the requirement for more opioids in smokers and actual demonstration of ADTBs (the fourth line of evidence) could be a result of differences in the metabolism of opioids between smokers and nonsmokers [20].…”