Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial

Hatsukami, Dorothy K.; Jensen, Joni A.; Carroll, Dana Mowls; Luo, Xianghua; Strayer, Lori G.; Cao, Qing; Hecht, Stephen S.; Murphy, Sharon E.; Carmella, Steven G.; Denlinger-Apte, Rachel L.; Colby, Suzanne; Strasser, Andrew A.; McClernon, F. Joseph; Tidey, Jennifer; Benowitz, Neal L.; Donny, Eric C.

doi:10.1016/j.lana.2024.100796

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Several studies have shown that smokers who switch from conventional tobacco cigarettes (e.g., 15 mg Nic) to very-low Nic content cigarettes (VLNC; e.g., 0.5 mg Nic or %0.33 of full flavor) still maintain considerable smoking levels (15-20 VLNCs/day; Benowitz et al, 2012;Donny et al, 2007Donny et al, , 2015, although more recent studies show lower rates of smoking VLNCs when alternative nicotine products (e.g. ENDS) are available (Hatsukami et al, 2024).…”

Section: Introductionmentioning

confidence: 99%

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

Smethells,

Wilde,

Muelken

et al. 2024

Preprint

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Backgroundβ-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm.MethodsThe pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 – 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic.Resultsβ-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ∼50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine’s discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal.Conclusionβ-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.

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Section: Introductionmentioning

confidence: 99%

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

Smethells,

Wilde,

Muelken

et al. 2024

Preprint

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Leveraging information from secondary endpoints to enhance dynamic borrowing across subpopulations

Wolf,

Vock,

Luo

et al. 2024

Biometrics

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Randomized trials seek efficient treatment effect estimation within target populations, yet scientific interest often also centers on subpopulations. Although there are typically too few subjects within each subpopulation to efficiently estimate these subpopulation treatment effects, one can gain precision by borrowing strength across subpopulations, as is the case in a basket trial. While dynamic borrowing has been proposed as an efficient approach to estimating subpopulation treatment effects on primary endpoints, additional efficiency could be gained by leveraging the information found in secondary endpoints. We propose a multisource exchangeability model (MEM) that incorporates secondary endpoints to more efficiently assess subpopulation exchangeability. Across simulation studies, our proposed model almost uniformly reduces the mean squared error when compared to the standard MEM that only considers data from the primary endpoint by gaining efficiency when subpopulations respond similarly to the treatment and reducing the magnitude of bias when the subpopulations are heterogeneous. We illustrate our model’s feasibility using data from a recently completed trial of very low nicotine content cigarettes to estimate the effect on abstinence from smoking within three priority subpopulations. Our proposed model led to increases in the effective sample size two to four times greater than under the standard MEM.

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Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial

Cited by 2 publications

References 26 publications

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

Leveraging information from secondary endpoints to enhance dynamic borrowing across subpopulations

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