– People who smoke and have opioid use disorder have a lower likelihood of drug use several months after initiating smoking cessation treatment if they are treated with nicotine replacement therapy rather than varenicline, new research suggests.

“Differences were not due to the pretreatment differences in drug use, which were covaried,” wrote Damaris J. Rohsenow, PhD, and colleagues at Brown University’s Center for Alcohol and Addiction Studies, Providence, R.I. “Results suggest it may be preferable to offer smokers with opioid use disorder [nicotine replacement therapy] rather than varenicline, given their lower adherence and more illicit drug use days during follow-up when given varenicline compared to [nicotine replacement therapy].”

They shared their research poster at the annual meeting of the College on Problems of Drug Dependence.

About 80%-90% of patients with OUD smoke, and those patients have a particularly difficult time with smoking cessation partly because of nonadherence to cessation medications, the authors noted. Smoking increases the risk of relapse from any substance use disorder, and pain – frequently comorbid with smoking – contributes to opioid use, they added.

Though smoking treatment has been shown not to increase drug or alcohol use, varenicline and nicotine replacement therapy have different effects on a4b2 nicotinic acetylcholinergic receptors (nAChRs). The authors noted that nicotine offers greater pain inhibition via full agonist effects across multiple nAChRs, whereas varenicline has only a partial agonist effect on a single nAChR.

“Smokers may receive more rewarding dopamine effects from the full nicotine agonist,” they wrote. The researchers therefore aimed to compare responses to nicotine replacement therapy and varenicline among smokers with and without OUD.

Ninety patients without OUD and 47 patients with it were randomly assigned to receive transdermal nicotine replacement therapy with placebo capsules or varenicline capsules with a placebo patch for 12 weeks with 3- and 6-month follow-ups. At baseline, those with OUD were significantly more likely to be white and slightly younger and have twice as many drug use days than those without the disorder.

Differences also existed between those with and without OUD for comorbid alcohol use disorder (55% vs. 81%), marijuana use disorder (32% vs. 19%) and cocaine use disorder (70% vs. 55%).

Those without OUD had slightly greater medication adherence, but with only borderline significance just among those taking varenicline. Loss to follow-up, meanwhile, was significantly greater for those with OUD in both treatment groups.

Most striking was the significantly higher number of drug use days among those with OUD who took varenicline vs. all other groups. Those patients had 16.5 drug use days at 4-6 months’ follow-up, compared with 0.13 days among those with OUD using nicotine replacement therapy (P less than .026). Among those without OUD, nicotine replacement therapy patients had 5 drug use days, and varenicline patients had 2.5 drug use days.

“Given interactions between nicotine and the opioid system and given that [nicotine replacement therapy] binds to more types of nAChRs than varenicline does, it is possible that [nicotine replacement therapy] dampens desire to use opiates compared to varenicline by stimulating more nAChRs,” the authors wrote. “Increasing nicotine dose may be better for smokers with opioid use disorder,” they added, though they noted the small size of the study and the need for replication with larger populations.

The research was funded by the National Institute on Drug Abuse and the Department of Veterans Affairs. The authors reported no disclosures.