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Virtual reality (VR) enables controlled cue exposure while capturing real-time multimodal data, including subjective experiences, behavioral patterns, and physiological responses, which offer a more implicit and dynamic approach to identifying addiction risk.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This pilot study examines whether subjective craving and psychophysiological responses (eg, eye gaze, heart rate, and electrodermal activity) to vaping-related cues in VR can distinguish young adults who vape from those who do not. Our secondary objective is to explore associations between these multimodal biomarkers and self-reported measures of craving, dependence, motivation to quit, and susceptibility to initiate vaping.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Bespoke VR scenes were developed with input from a youth advisory board to ensure ecological validity. Forty young adults aged 18 to 21 years (20 vapers and 20 nonvapers) will complete a single laboratory session. Participants will experience 3 VR scenes (neutral baseline, vaping cues without social pressure, and vaping cues with social pressure in counterbalanced order). Eye gaze, heart rate, and electrodermal activity will be recorded continuously. Participants will complete standardized assessments of craving, sense of presence, and social presence in VR after each cue scene, followed by a short interview at the end. Quantitative data will be analyzed using mixed-model ANOVAs, correlation metrics, and exploratory regularized regression analyses to examine relationships between physiological responses, behavioral measures, and vaping status.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The project received institutional review board approval in August 2025 and was registered publicly in the Open Science Framework in November 2025. Development of the VR stimuli was completed in December 2025. Participant recruitment and data collection began in February 2026, and 7 participants have been enrolled as of March 2026.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This protocol outlines a pilot study integrating immersive VR and multimodal biometrics to examine vaping cue reactivity in young adults. The findings will guide the development and evaluation of VR-based psychophysiological tools for identifying early markers of nicotine use risk. This work will also lay the foundation for adapting the approach to younger adolescents to support scalable early detection and prevention of nicotine addiction and initiation.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/89382","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:35:06Z","timestamp":1773048906000},"page":"e89382-e89382","source":"Crossref","is-referenced-by-count":2,"title":["Psychophysiological Responses in Virtual Reality for Assessing Current Nicotine Use and Future Addiction Risk Among Young Adults: Protocol for a Mixed Methods Study"],"prefix":"10.2196","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-2488","authenticated-orcid":false,"given":"Shu","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3171-4922","authenticated-orcid":false,"given":"Shawn","family":"Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5121-095X","authenticated-orcid":false,"given":"Chris","family":"Shia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9453-3888","authenticated-orcid":false,"given":"Michael","family":"Gancz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-4507","authenticated-orcid":false,"given":"Deepa","family":"Camenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5792-3605","authenticated-orcid":false,"given":"Kammarauche","family":"Aneni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-9912","authenticated-orcid":false,"given":"Asher","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-7767","authenticated-orcid":false,"given":"Kimberly","family":"Hieftje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"11","key":"R1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.40671","article-title":"Nicotine addiction and intensity of e-cigarette use by adolescents in the US, 2014 to 2021","volume":"5","author":"Glantz","journal-title":"JAMA Netw Open"},{"issue":"2","key":"R2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/npp.2008.96","article-title":"Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats","volume":"34","author":"Counotte","journal-title":"Neuropsychopharmacol"},{"issue":"12","key":"R3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012120","article-title":"Short- and long-term consequences of nicotine exposure during adolescence for prefrontal cortex neuronal network function","volume":"2","author":"Goriounova","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"1","key":"R4","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02961-5","article-title":"Tobacco and COPD: presenting the World Health Organization (WHO) Tobacco Knowledge Summary","volume":"25","author":"Lu","journal-title":"Respir Res"},{"issue":"1","key":"R5","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-021-10935-1","article-title":"Association between electronic cigarette use and tobacco cigarette smoking initiation in adolescents: a systematic review and meta-analysis","volume":"21","author":"O\u2019Brien","journal-title":"BMC Public Health"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpeds.2024.100190","article-title":"The adverse effects of vaping in young people","volume":"9","author":"Meehan","journal-title":"Glob Pediatr"},{"key":"R7","unstructured":"Key substance use and mental health indicators in the United States: results from the 2024 National Survey on Drug Use and Health. 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