Opioid Use and Rate of Nicotine Metabolism among Pregnant Smokers

Author Department


Document Type

Article, Peer-reviewed

Publication Date




Smokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers.


We recruited pregnant women who smoked ≥ 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (3-hydroxycotinine (3HC)/cotinine) (NMR)-a biomarker of nicotine metabolism-OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking.


Among 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n=14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p=0.0007), serum 3HC (81.0 vs. 42.0 ng/mL, p=0.0001), and NMR (0.63 vs. 0.43, p<0.0001). Additionally, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p=0.0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p=0.012), specifically methadone-maintained smokers (p=0.024), than non-OU smokers.


Our preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance.


Among pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users-the majority of whom were on methadone maintenance-compared to non-users, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.