Evidence map›Paper›PMID 41520411›Full record

ArticleDrug and alcohol dependence2026

β-Nicotyrine and e-cigarette abuse liability II: Behavioral economic demand and intracranial self-stimulation in rats.

J R Smethells, S Wilde, P Muelken, A C Harris, M G LeSage

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Article in Drug and alcohol dependence, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

J R SmethellsHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA. Electronic address: smet0011@umn.edu.
S WildeHennepin Healthcare Research Institute, Minneapolis, MN, USA.
P MuelkenHennepin Healthcare Research Institute, Minneapolis, MN, USA.
A C HarrisHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
M G LeSageHennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.

Funding

An evaluation of Beta-nicotyrine as a potential contributor to the abuse liability of e-cigarettesR01DA053608 · NIDA · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI SMETHELLS, JOHN RICHARD · 2021 to 2023
$989k
NIDA NIH HHS R01 DA053608
6 · The paper itself

Abstract

backgroundGiven the prominence of electronic nicotine delivery systems (ENDS), understanding the product characteristics that underlie ENDS abuse liabilty is a public health research priority. β-Nicotyrine (β-Nic) is a uniquely prevalent constituent (up to 25 % of nicotine [Nic] levels) in ENDS aerosols that may contribute to ENDS abuse liability. Previously, we found clinically relevant concentration of β-Nic doubled the elimination half-life and prolong the interoceptive (discriminative stimulus) properties of Nic in rats, but that it had little or no psychoactive effects itself. The present study used i.v. self-administration (23 hrs/day) and intracranial self-stimulation (ICSS) paradigms to further evaluate if β-Nic alone has abuse liability or if it enhances the abuse liability of Nic.

methodsWe examined if β-Nic (> 25 % of Nic levels) substitutes for Nic (0.03mg/kg/inf) during drug self-administration, and whether combinations of Nic and β-Nic alter the acquisition and behavioral economic demand of i.v. Nic. Reinforcement-enhancing and aversive effects of β-Nic alone or in combination with Nic were also evaluated using ICSS.

resultsModerately high β-Nic doses (0.03 & 0.10mg/kg/inf) increased demand for Nic (0.03mg/kg/inf). β-Nic alone did not maintain self-administration, affect ICSS, or influence the effects of Nic on ICSS.

conclusionβ-Nic itself does not have abuse potential in either i.v. self-administration or ICSS models, but it does increase the reinforcing efficacy of self-administered Nic. As such, β-Nic may play a role in the abuse liability of ENDS, which has important treatment and regulatory implications.

Indexed as

Electronic Nicotine Delivery SystemsNicotineNicotinic AgonistsSelf StimulationAnimalsConditioning, OperantMaleRatsRats, Sprague-DawleySelf AdministrationNicotineNicotinic AgonistsAbuse liabilityBehavioral economic demandBeta-NicotyrineIntracranial, self-stimulationNicotineRat

Identifiers

PMID41520411
PMCPMC12950280

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.