{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:40:23Z","timestamp":1792190423062,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Mandated reduction of the nicotine content of cigarettes to reduce addictiveness to minimal levels has the potential to substantially reduce combusted cigarette use and promote public health. This paper examined the hypothesis that when people who smoke cigarettes are switched to very low nicotine content (VLNC) cigarettes and provided with access to non\u2010combusted alternative nicotine delivery systems (ANDS), they will titrate nicotine to maintain baseline levels of nicotine intake with the use of ANDS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a secondary analysis of a recently published randomized clinical trial. Clinical trial number NCT03272685.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Multicenter clinical trial conducted in the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>438 individuals who smoked 5 to 40 cigarettes per day, mean age 44 (range 20\u201373).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Smokers were randomized 1:1 for 12\u2009weeks of smoking Spectrum brand research cigarettes containing VLNC (0.4\u00a0mg nicotine\/g tobacco) or normal nicotine content (15.8\u00a0mg nicotine\/g, NNC). Participants purchased tobacco products from an experimental marketplace containing non\u2010combusted ANDS, including electronic cigarettes, nicotine replacement medications and oral nicotine products.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Measures taken at baseline, 4, 8 and 12\u2009weeks included cigarettes smoked per day (CPD) and measures of ANDS use, assessed using past 3\u2010day daily diary data, which would roughly account for nicotine intake as measured by urine total nicotine equivalents (TNE). Based on self\u2010report and biomarker data at weeks 4, 8 and 12, we characterized three product\u2010using groups of participants as cigarette\u2010only users, ANDS\u2010only users and dual users. Nicotine titration was assessed as the ratio of urine TNE at various research cigarette study weeks compared with baseline (smoking their own cigarettes). Combusted product abstinence was examined using expired carbon monoxide (CO) and adherence to smoking VLNC by urine anatabine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Median titration at 12\u2009weeks in cigarette\u2010only participants was 0.84 (interquartile range 0.68\u20131.18) in the NNC group and 0.05 (0.01\u20130.12) in the VLNC group. Median titration at 12\u2009weeks in ANDS\u2010only participants was 0.81 (0.69\u20131.16) in the NNC group and 0.89 (0.49\u20131.58) in the VLNC group. Median titration at 12\u2009weeks in dual use participants was 1.0 (0.78\u20131.29) in the NNC group and 0.91 (0.61\u20131.25) in the VLNC group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Most adults who smoke, when switched to very low nicotine content cigarettes, will use available alternative nicotine delivery systems (ANDS) to supplement their intake of nicotine. Provision of ANDS appears to be associated with a high degree of nicotine titration. Making less harmful ANDS widely available may make a mandated nicotine reduction intervention more acceptable to people who smoke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70385","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:19:33Z","timestamp":1773908373000},"page":"1899-1906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Titration of nicotine intake in smokers switching to reduced nicotine content cigarettes with access to alternative nicotine systems: Secondary analysis of a randomized clinical trial"],"prefix":"10.1111","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-8124","authenticated-orcid":false,"given":"Neal L.","family":"Benowitz","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, School of Public Health University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-6582","authenticated-orcid":false,"given":"Xianghua","family":"Luo","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, School of Public Health University of Minnesota  Minneapolis MN USA"},{"name":"Masonic Cancer Center University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Joseph","family":"McClernon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, School of Medicine Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tidey","sequence":"additional","affiliation":[{"name":"Center for Alcohol and Addiction Studies, School of Public Health Brown University  Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Strasser","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2027-5936","authenticated-orcid":false,"given":"Suzanne","family":"Colby","sequence":"additional","affiliation":[{"name":"Center for Alcohol and Addiction Studies, School of Public Health Brown University  Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Donny","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, School of Medicine Wake Forest University  Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-2609","authenticated-orcid":false,"given":"Dorothy K.","family":"Hatsukami","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center University of Minnesota  Minneapolis MN USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Medical School University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1714617"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199407143310212"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1502403"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/jama.2018.11473","article-title":"Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial","volume":"320","author":"Hatsukami DK","year":"2018","journal-title":"JAMA"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntz101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0275522"},{"key":"e_1_2_10_8_1","unstructured":"Department of Health and Human Services Food and Drug Administration.Tobacco Product Standard for Nicotine Yield of Cigarettes and Certain Other Combusted Tobacco Products [Internet].2025; 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