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Non-nicotine compounds that contribute to abuse liability of electronic nicotine delivery systems

Award Number: R01DA064914
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Non-nicotine compounds that contribute to abuse liability of electronic nicotine delivery systems - SUMMARY / ABSTRACT Nicotine and tobacco use disorder is among the greatest preventable threats to US public health. The rapid market growth of electronic nicotine delivery systems (ENDS) makes them of particular concern, especially given their popularity with youth and young adults. Accordingly, it is critical to understand the basis of the abuse liability (the likelihood that a tobacco product sustains long-term use and dependence) of ENDS. Abuse liability is driven by a balance between nicotine’s positive reinforcing, rewarding, and withdrawal-relieving effects on one hand, and nicotine’s aversive and reward-suppressing effects on the other. Specific nicotinic acetylcholine receptor (nAChR) subtypes mediate these effects. Our hypothesis, supported by an extensive literature, is that large numbers of non-nicotine compounds are pharmacologically active at nAChR subtypes associated with abuse liability and so contribute significantly to this balance (and, therefore, to abuse liability of tobacco products). ENDS liquids contain a wide and growing range of constituents; interactions of almost all of these compounds with relevant nAChR subtypes are wholly uncharacterized. Therefore, this application’s overall goal is to 1) use high-throughput screening (HTS) methods to accelerate the comprehensive identification and characterization of non-nicotine compounds in ENDS that have functional activity at nAChR subtypes with relevance to abuse liability, and 2) demonstrate those active compounds’ relevance to tobacco product abuse liability using a first- of-its kind, inhalation-only, preclinical ENDS exposure model. Published literature consistently indicates a significant effect of sex as a biological variable (SABV) on the balance of reasons that individuals choose to use tobacco products and how they experience withdrawal. Accordingly, we will investigate whether there are significant differences between ENDS preferred by males and females (regarding the presence of nAChR-active compounds), and in the outcomes recorded when testing the nAChR-active compounds using the preclinical model. Success will produce critically needed insights into the basis of abuse liability of the popular, and highly diverse, category of ENDS. By considering SABV, this study may also uncover important new differences in the bases of tobacco use disorder between male and female subjects. A unique advantage of using rapid, HTS methods is that it will allow us to keep pace with the constantly-evolving ENDS market. By continuously updating our knowledge of specific, novel, constituents in ENDS, we will be able to monitor for changes in the basis of abuse liability of ENDS products. While not our primary objective, this information could be used to inform tobacco product regulation to limit constituents that increase abuse liability, contributing to protection of public health. Further, this closely-integrated HTS and preclinical-testing platform can also be adapted as needed to address new and emerging categories of tobacco products.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $591,405 )
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	001	1	7/22/2026	NEW	$0
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	1	7/6/2026	NEW	$591,405
														Subtotal = $591,405

Grand Total All Awards = $591,405

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Non-nicotine compounds that contribute to abuse liability of electronic nicotine delivery systems

Award Number: R01DA064914

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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