Trial Tests E-Cigarettes Against Nicotine Replacement for Smokers in Opioid Treatment

Smoking rates among people receiving treatment for opioid use disorder are exceptionally high, and a new randomized controlled trial now underway aims to determine whether electronic cigarettes could serve as a practical harm-reduction tool for this population. The study, described in a protocol published in Harm Reduction Journal, compares a standardized research electronic cigarette developed by the National Institute on Drug Abuse against combination nicotine replacement therapy, with both groups also receiving telehealth counseling.

The trial is multi-site, open-label, and randomizes 302 participants who smoke combustible cigarettes and are enrolled in opioid use disorder treatment programs. Participants are assigned in a 1:1 ratio to either the electronic cigarette arm or the nicotine replacement therapy arm. Everyone receives up to five telehealth counseling sessions grounded in motivational interviewing and harm-reduction principles, a design intended to isolate the effect of the nicotine delivery device itself while providing identical behavioral support across both groups.

The primary outcome is the proportion of participants achieving a 100% reduction in cigarettes per day at the end of the eight-week intervention, verified objectively by an exhaled carbon monoxide level below 6 parts per million. Secondary outcomes extend the picture over a longer horizon and include the proportion achieving complete cigarettes-per-day reduction at six-month follow-up, reductions in cigarettes per day at both time points, and self-reported health outcomes such as health-related quality of life.

A distinctive feature of the trial is its biomarker component. Among participants who report at least a 50% reduction in cigarettes per day, the researchers will measure changes in urinary NNAL — 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol — a metabolite that reflects exposure to tobacco-specific carcinogenic toxicants, comparing levels at eight weeks against baseline. This allows the study to assess not just whether people smoke fewer combustible cigarettes, but whether their exposure to harmful combustion products actually declines.

The rationale for testing e-cigarettes in this group rests on two points highlighted by the investigators: combustible cigarette smoking is exceptionally common among people in opioid use disorder treatment, and e-cigarettes may deliver nicotine while replicating the behavioral rituals of smoking, potentially offering an alternative to nicotine replacement therapy that some smokers find easier to adopt.

It is important to note that this publication is a study protocol, not a results paper. Recruitment and treatment are ongoing, and no efficacy findings are yet available. The authors state their hypothesis that the electronic cigarette arm will show higher combustible cigarette abstinence and greater cigarettes-per-day reduction than the nicotine replacement therapy arm, with parallel improvements in toxicant exposure and secondary outcomes, but these remain expectations to be tested rather than observed results.

If the hypotheses are borne out, the findings could clarify whether electronic cigarettes combined with telehealth counseling constitute a viable harm-reduction strategy for adults in opioid use disorder treatment programs who smoke, and could inform future tobacco treatment guidelines. The trial is registered at ClinicalTrials.gov under identifier NCT05722561, and the article was published open access on 8 October 2026.

Subject of Research: A randomized controlled trial protocol comparing e-cigarettes with nicotine replacement therapy for smoking reduction among people in opioid use disorder treatment

Article Title: Electronic cigarettes as a harm reduction strategy for combustible cigarette smoking among people in opioid use disorder treatment programs: protocol for an open-label two-arm randomized controlled trial

Article References: El-Shahawy, O., Abbasi-Kangevari, M., Gallardo Castillo, I., Wint, A., He, M., Stevens, E. R., Nicholson, A., Benowitz, N. L., Lynn, M., Simon, R., Bhakta, H., Sherman, S. E., Schatz, D., Cleland, C. M., Lee, J. D., & Nahvi, S. (2026). Electronic cigarettes as a harm reduction strategy for combustible cigarette smoking among people in opioid use disorder treatment programs: protocol for an open-label two-arm randomized controlled trial. Harm Reduction Journal. https://doi.org/10.1186/s12954-026-01536-5

Image Credits: AI Generated

DOI: 10.1186/s12954-026-01536-5

Keywords: electronic cigarettes, opioid use disorder, harm reduction, nicotine replacement therapy, randomized controlled trial, smoking cessation, telehealth counseling, NNAL, carbon monoxide, tobacco toxicants, study protocol, Harm Reduction Journal