Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States

Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States Sven E. Jordt, Sairam V. Jabba This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5110349/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: In 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from regulation. It is unknown whether the use of 6MN has spread to the oral nicotine pouch product category that has become increasingly popular. Methods: Industry reports and the USPTO database were searched for informationon 6-methyl nicotine products. The search terms “Metatine”, “Nixotine”, “Imotine” and “pouches” were shortlisted and used to identify US-marketed pouch products. Ingredient contents were compared to popular products, and safety warnings and regulatory statements assessed in context with US state and federal regulations. Results: Two US-based brands, "MG" and "Hippotine" pouches, were identified in August 2024, advertised to contain "Imotine"-trademarked 6MN. MG Pouches are marketed in four youth-appealing flavors. "Hippotine"-branded pouches are marketed in two flavors. 6MN contents ranged between 8mg - 25mg with almost identical ingredient lists otherwise. Products list extensive addiction and health warnings, including warnings not to operate vehicles. Vendors state that these are not a tobacco product, implicating that federal and state tobacco regulations do not apply. Conclusions: The spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially given the high 6MN contents that exceed nicotine contents in popular US-marketed oral nicotine pouch products. Legislators and regulators need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of tobacco flavor bans and other regulations. Epidemiology Marketing Health Policy Addiction Non-cigarette tobacco products Tobacco Industry Nicotine Nicotine analogue Figures Figure 1 Introduction In 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from FDA regulation [ 1 ]. Since then, several disposable e-cigarette products and refill liquids containing 6MN appeared on the US market, with the compound branded “Metatine” or “Nixotine”, the latter mixed with nicotinamide [ 2 ]. An additional trademark, “Imotine”, was registered for 6MN, marketed by the company Novel Compounds [ 3 – 5 ]. Oral nicotine pouches (ONP) represent a new tobacco product category with rapidly growing sales in the United States and worldwide [ 6 ]. It is unknown whether the use of 6MN has spread to this product category. Methods Industry reports, Google Patents and the USPTO database were searched for information, patent applications and trademarks for 6-methyl nicotine products. The search terms “Metatine”, “Nixotine”, “Imotine”, “6-methyl nicotine” (and variations thereof) and “pouches” were shortlisted and used to identify US-marketed pouch products. Products were purchased from web merchants to confirm availability. Ingredient contents were reviewed and compared with ingredients in market-leading Oral Nicotine Pouch products. Marketing and safety claims were reviewed and regulatory statements assessed in context with regulations of US states, especially California, and federal laws and regulations. Results and Discussion We used the search terms “Metatine”, “Nixotine” or “Imotine” and “pouch” to search for 6MN-containing oral pouch products marketed by web merchants. In August 2024, we identified two US-based brands, “MG” and “Hippotine” pouches, advertised to contain “Imotine”. No “Metatine”, or “Nixotine” pouch products were identified. “MG” pouches are marketed by Upperdeckys.com, a vendor of caffeine-containing “Energy” pouches. “Hippotine” pouches are marketed by the web merchant Happyhippo.com, a vendor of Kratom, an herbal extract containing opioid receptor agonists [7 8]. MG Pouches are marketed in four flavors, Cool Mint (8 mg Imotine per pouch), Buzzin Berry (8 mg), Wintergreen (15 mg) and Orange Creamsicle (25 mg) (Table 1 ). Hippotine-branded pouches are marketed in two flavors, Guava Juice (15 mg Imotine per pouch) and Wintergreen (25 mg) (Table 1 ). The listed 6-methyl nicotine contents of the newly introduced products are either identical (8 mg), or by far exceed (15mg, 25mg), the maximal nicotine contents of the most popular US-marketed nicotine pouch products (Zyn, Velo, On!). Both brands provide almost identical ingredient lists on the back of the cans, containing “Coconut Fiber” (MG) or “Coconut Coir” (Hippotine), “Vegetable Glycerin, Palm Oil, Xylitol, Natural Flavor, Water, Imotine™, Sodium Carbonate, Xanthan Gum, Stevia, Salt”, suggesting they are produced by the same manufacturer. Table 1 Brands, 6MN trademarks,flavors and listed 6MN contents in US-marketed oral pouch products Brand 6MN Trademark Flavor 6MN Strength/pouch MG Imotine Cool Mint 8 mg Buzzin Berry 8 mg Wintergreen 15 mg Orange Creamsicle 25 mg Hippotine Imotine Guava Juice 15 mg Wintergreen 25 mg Extensive addiction and health warning are provided: “Imotine™ is chemically distinct from nicotine. It may still be addictive, may have toxicity profile similar to Nicotine, and should only be used by current adult tobacco users and never by minors (Persons under the age of 21).“ [ 8 ] “Do not use if you are pregnant, nursing or may become pregnant. Consult your doctor before using if you have any diagnosed health conditions. Consult a Doctor before initial and future use if you are on any medications.“ (Fig. 1 ) “Use Hippotine at your own risk.” (Fig. 1 ) Additionally, a warning usually not associated with tobacco products is included: “Warning: Do not operate a vehicle or heavy machinery when taking this product. “ (Fig. 1 ) Both brands state, either on their website (MG) or on the can (Hippotine) that “This product is not intended to diagnose, treat, cure, or prevent any disease or condition.”, likely to pre-empt regulation of the products by FDA as drugs (Fig. 1 ) [ 8 ]. The vendor also states that “Imotine™ is not considered a “tobacco product”.”, suggesting that tobacco regulatory restrictions do not apply [ 9 ]. Hippotine pouches are advertised as “Available to Californians (not subject to flavored pouch restriction)”, aiming to undermine California's ban on characterizing flavors that extends to oral nicotine pouches [ 7 ]. Conclusions The spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially because of the high listed 6MN contents of the newly introduced products. Given the higher potency of 6MN compared to nicotine in pharmacological studies, regulators need to rapidly assess the potential public health threats associated with these products [ 1 ]. Legislators and regulators also need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of flavor bans and other regulations. Declarations Disclaimer The funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; nor in the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the views of National institutes of Health or the Food and Drug Administration. Competing Interests The authors have no disclosures to report. Funding This work was supported by grants R01DA060884 and U54DA036151 (Yale Tobacco Center of Regulatory Science) to SEJ from the National Institute on Drug Abuse and by the United States Food and Drug Administration Center for Tobacco Products. Author Contributions SEJ and SVJ conceptualized and designed the study. SEJ wrote the first draft of the paper; SVJ provided advice on product choice and figures design. SEJ and SVJ contributed to revision of the manuscript. All authors critically reviewed, edited, and approved the final draft before submission. SEJ attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. References Jordt SE, Jabba SV, Zettler PJ et al (2024) Spree Bar, a vaping system delivering a synthetic nicotine analogue, marketed in the USA as 'PMTA exempt'. Tob Control. 10.1136/tc-2023-058469 Erythropel HC, Jabba SV, Silinski P et al (2024) Variability in Constituents of E-Cigarette Products Containing Nicotine Analogues. JAMA 332(9):753–755. 10.1001/jama.2024.12408 Bowen MD, IMOTINE:, USPTO Trademarks (2023) ; Available: https://uspto.report/TM/97838222 [Accessed 09/16/2024] Carmines E, Misra M, Benaim S, Imotine™: A Novel Non-nicotine Compound with CNS activity: 2023. Available: https://web.archive.org/web/20240102003453/https://chemular.com/2023/09/21/imotine/ [Accessed 12/20/2023] Novel Compounds L, Imotine.com (2023) Available: https://web.archive.org/web/20230731140615/https://imotine.com/ [Accessed 12/20/2023] Duan Z, Henriksen L, Vallone D et al (2024) Nicotine pouch marketing strategies in the USA: an analysis of Zyn, On! and Velo. Tob Control 33(2):154–163. 10.1136/tc-2022-057360 HappyHippo Hippotine (Imotine™): 2024. Available: https://happyhippo.com/products/buy-imotine [Accessed 09/13/2024] Upperdeckys MG by, Upperdeckys (2024) Available: https://upperdeckys.com/pages/mg [Accessed 09/13/2024] Upperdeckys. What Is ITM (2024) Available: https://upperdeckys.com/pages/imotine%E2%84%A2 [Accessed 08/21/2024] Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5110349","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":355877600,"identity":"8561ec2e-4e8a-47b7-8a82-9441a09a8b28","order_by":0,"name":"Sven E. Jordt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYNACHiA+wHxAguEAiJdArJZjbAmkaAGBYzwGxGmRn5F87AGDjE0+3/2ej7d5ztgw8LPnGODVYnAjLd2AgSfNcuYx3s3WPDfSGCR73hDQwnPGTIKB57CBwTHebdI8Hw4DDSFgi3zP+W9QLTzPgFr+M9gT0sJwvIcNpoVNmufGAQYDCUJ+Od5mJpHAk2YgeSzN2HLOmWQeiTPPCvA7rJn5mcTHHhsDvsOHH954c8xOjr89eQN+h4FAYg+CzUNYORj8IFLdKBgFo2AUjEwAAH/sRAicOJiYAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-6171-5622","institution":"Duke University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Sven","middleName":"E.","lastName":"Jordt","suffix":""},{"id":355877601,"identity":"31a66812-827f-423d-bea6-249bf4a32159","order_by":1,"name":"Sairam V. Jabba","email":"","orcid":"https://orcid.org/0000-0003-0646-3519","institution":"Duke University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sairam","middleName":"V.","lastName":"Jabba","suffix":""}],"badges":[],"createdAt":"2024-09-18 13:17:21","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5110349/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5110349/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64882161,"identity":"94a9d374-40c0-4a16-8f8f-d5f010544a09","added_by":"auto","created_at":"2024-09-20 03:43:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1530557,"visible":true,"origin":"","legend":"\u003cp\u003eOral pouch products containing \u003cstrong\u003e“\u003c/strong\u003eImotine”-branded 6-methyl nicotine\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003ePhotographs of Orange Creamsicle-flavored “MG” pouches can purchased by the authors, labelled to contain 25mg “Imotine” per pouch. Left: Front of can, Middle: Back of can, Right: “Imotine” content, ingredients list.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB. \u003c/strong\u003eWintergreen-flavored “Hippotine” pouches can, labelled to contain 25mg “Imotine” . Left: Front of can, Right: Back of can.\u003c/p\u003e","description":"","filename":"Figure1png.png","url":"https://assets-eu.researchsquare.com/files/rs-5110349/v1/248e68cef12ec460e942075c.png"},{"id":64882162,"identity":"1f4b7fa2-c0b1-41a1-9a38-69781aa2f1b9","added_by":"auto","created_at":"2024-09-20 03:43:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2543346,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5110349/v1/afbe030b-5731-4223-8100-451984a57c8f.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eIntroduction of Nicotine Analogue-Containing Oral Pouch Products in the United States\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from FDA regulation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Since then, several disposable e-cigarette products and refill liquids containing 6MN appeared on the US market, with the compound branded \u0026ldquo;Metatine\u0026rdquo; or \u0026ldquo;Nixotine\u0026rdquo;, the latter mixed with nicotinamide [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. An additional trademark, \u0026ldquo;Imotine\u0026rdquo;, was registered for 6MN, marketed by the company Novel Compounds [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOral nicotine pouches (ONP) represent a new tobacco product category with rapidly growing sales in the United States and worldwide [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It is unknown whether the use of 6MN has spread to this product category.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eIndustry reports, Google Patents and the USPTO database were searched for information, patent applications and trademarks for 6-methyl nicotine products. The search terms \u0026ldquo;Metatine\u0026rdquo;, \u0026ldquo;Nixotine\u0026rdquo;, \u0026ldquo;Imotine\u0026rdquo;, \u0026ldquo;6-methyl nicotine\u0026rdquo; (and variations thereof) and \u0026ldquo;pouches\u0026rdquo; were shortlisted and used to identify US-marketed pouch products. Products were purchased from web merchants to confirm availability. Ingredient contents were reviewed and compared with ingredients in market-leading Oral Nicotine Pouch products. Marketing and safety claims were reviewed and regulatory statements assessed in context with regulations of US states, especially California, and federal laws and regulations.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eWe used the search terms \u0026ldquo;Metatine\u0026rdquo;, \u0026ldquo;Nixotine\u0026rdquo; or \u0026ldquo;Imotine\u0026rdquo; and \u0026ldquo;pouch\u0026rdquo; to search for 6MN-containing oral pouch products marketed by web merchants. In August 2024, we identified two US-based brands, \u0026ldquo;MG\u0026rdquo; and \u0026ldquo;Hippotine\u0026rdquo; pouches, advertised to contain \u0026ldquo;Imotine\u0026rdquo;. No \u0026ldquo;Metatine\u0026rdquo;, or \u0026ldquo;Nixotine\u0026rdquo; pouch products were identified. \u0026ldquo;MG\u0026rdquo; pouches are marketed by Upperdeckys.com, a vendor of caffeine-containing \u0026ldquo;Energy\u0026rdquo; pouches. \u0026ldquo;Hippotine\u0026rdquo; pouches are marketed by the web merchant Happyhippo.com, a vendor of Kratom, an herbal extract containing opioid receptor agonists [7 8].\u003c/p\u003e \u003cp\u003eMG Pouches are marketed in four flavors, Cool Mint (8 mg Imotine per pouch), Buzzin Berry (8 mg), Wintergreen (15 mg) and Orange Creamsicle (25 mg) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hippotine-branded pouches are marketed in two flavors, Guava Juice (15 mg Imotine per pouch) and Wintergreen (25 mg) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The listed 6-methyl nicotine contents of the newly introduced products are either identical (8 mg), or by far exceed (15mg, 25mg), the maximal nicotine contents of the most popular US-marketed nicotine pouch products (Zyn, Velo, On!). Both brands provide almost identical ingredient lists on the back of the cans, containing \u0026ldquo;Coconut Fiber\u0026rdquo; (MG) or \u0026ldquo;Coconut Coir\u0026rdquo; (Hippotine), \u0026ldquo;Vegetable Glycerin, Palm Oil, Xylitol, Natural Flavor, Water, Imotine\u0026trade;, Sodium Carbonate, Xanthan Gum, Stevia, Salt\u0026rdquo;, suggesting they are produced by the same manufacturer.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBrands, 6MN trademarks,flavors and listed 6MN contents in US-marketed oral pouch products\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrand\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6MN Trademark\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFlavor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6MN Strength/pouch\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImotine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCool Mint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBuzzin Berry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWintergreen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOrange Creamsicle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHippotine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImotine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuava Juice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWintergreen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 mg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eExtensive addiction and health warning are provided:\u003c/p\u003e \u003cp\u003e\u0026ldquo;Imotine\u0026trade; is chemically distinct from nicotine. It may still be addictive, may have toxicity profile similar to Nicotine, and should only be used by current adult tobacco users and never by minors (Persons under the age of 21).\u0026ldquo; [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e\u0026ldquo;Do not use if you are pregnant, nursing or may become pregnant. Consult your doctor before using if you have any diagnosed health conditions. Consult a Doctor before initial and future use if you are on any medications.\u0026ldquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u0026ldquo;Use Hippotine at your own risk.\u0026rdquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAdditionally, a warning usually not associated with tobacco products is included: \u0026ldquo;Warning: Do not operate a vehicle or heavy machinery when taking this product. \u0026ldquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBoth brands state, either on their website (MG) or on the can (Hippotine) that \u0026ldquo;This product is not intended to diagnose, treat, cure, or prevent any disease or condition.\u0026rdquo;, likely to pre-empt regulation of the products by FDA as drugs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The vendor also states that \u0026ldquo;Imotine\u0026trade; is not considered a \u0026ldquo;tobacco product\u0026rdquo;.\u0026rdquo;, suggesting that tobacco regulatory restrictions do not apply [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Hippotine pouches are advertised as \u0026ldquo;Available to Californians (not subject to flavored pouch restriction)\u0026rdquo;, aiming to undermine California's ban on characterizing flavors that extends to oral nicotine pouches [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially because of the high listed 6MN contents of the newly introduced products. Given the higher potency of 6MN compared to nicotine in pharmacological studies, regulators need to rapidly assess the potential public health threats associated with these products [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Legislators and regulators also need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of flavor bans and other regulations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eDisclaimer\u003c/h2\u003e \u003cp\u003eThe funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; nor in the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the views of National institutes of Health or the Food and Drug Administration.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors have no disclosures to report.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by grants R01DA060884 and U54DA036151 (Yale Tobacco Center of Regulatory Science) to SEJ from the National Institute on Drug Abuse and by the United States Food and Drug Administration Center for Tobacco Products.\u003c/p\u003e\u003ch2\u003eAuthor Contributions\u003c/h2\u003e \u003cp\u003eSEJ and SVJ conceptualized and designed the study. SEJ wrote the first draft of the paper; SVJ provided advice on product choice and figures design. SEJ and SVJ contributed to revision of the manuscript. All authors critically reviewed, edited, and approved the final draft before submission. SEJ attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJordt SE, Jabba SV, Zettler PJ et al (2024) Spree Bar, a vaping system delivering a synthetic nicotine analogue, marketed in the USA as 'PMTA exempt'. Tob Control. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/tc-2023-058469\u003c/span\u003e\u003cspan address=\"10.1136/tc-2023-058469\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErythropel HC, Jabba SV, Silinski P et al (2024) Variability in Constituents of E-Cigarette Products Containing Nicotine Analogues. JAMA 332(9):753\u0026ndash;755. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2024.12408\u003c/span\u003e\u003cspan address=\"10.1001/jama.2024.12408\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBowen MD, IMOTINE:, USPTO Trademarks (2023) ; Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://uspto.report/TM/97838222\u003c/span\u003e\u003cspan address=\"https://uspto.report/TM/97838222\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 09/16/2024]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarmines E, Misra M, Benaim S, Imotine\u0026trade;: A Novel Non-nicotine Compound with CNS activity: 2023. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://web.archive.org/web/20240102003453/https://chemular.com/2023/09/21/imotine/\u003c/span\u003e\u003cspan address=\"https://web.archive.org/web/20240102003453/https://chemular.com/2023/09/21/imotine/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 12/20/2023]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovel Compounds L, Imotine.com (2023) Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://web.archive.org/web/20230731140615/https://imotine.com/\u003c/span\u003e\u003cspan address=\"https://web.archive.org/web/20230731140615/https://imotine.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 12/20/2023]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuan Z, Henriksen L, Vallone D et al (2024) Nicotine pouch marketing strategies in the USA: an analysis of Zyn, On! and Velo. Tob Control 33(2):154\u0026ndash;163. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/tc-2022-057360\u003c/span\u003e\u003cspan address=\"10.1136/tc-2022-057360\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHappyHippo Hippotine (Imotine\u0026trade;): 2024. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://happyhippo.com/products/buy-imotine\u003c/span\u003e\u003cspan address=\"https://happyhippo.com/products/buy-imotine\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 09/13/2024]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUpperdeckys MG by, Upperdeckys (2024) Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://upperdeckys.com/pages/mg\u003c/span\u003e\u003cspan address=\"https://upperdeckys.com/pages/mg\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 09/13/2024]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUpperdeckys. What Is ITM (2024) Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://upperdeckys.com/pages/imotine%E2%84%A2\u003c/span\u003e\u003cspan address=\"https://upperdeckys.com/pages/imotine%E2%84%A2\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed 08/21/2024]\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"361e58ec-1931-479b-8372-30d27ce5d24e","identifier":"10.13039/100000026","name":"National Institute on Drug Abuse","awardNumber":"R01DA060884","order_by":0},{"identity":"2979f456-5d2d-4b28-bc21-7d386cff2b6d","identifier":"10.13039/100000026","name":"National Institute on Drug Abuse","awardNumber":"U54DA036151 ","order_by":1}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Duke University School of Medicine","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Addiction, Non-cigarette tobacco products, Tobacco Industry, Nicotine, Nicotine analogue","lastPublishedDoi":"10.21203/rs.3.rs-5110349/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5110349/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e In 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from regulation. It is unknown whether the use of 6MN has spread to the oral nicotine pouch product category that has become increasingly popular.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Industry reports and the USPTO database were searched for informationon 6-methyl nicotine products. The search terms “Metatine”, “Nixotine”, “Imotine” and “pouches” were shortlisted and used to identify US-marketed pouch products. Ingredient contents were compared to popular products, and safety warnings and regulatory statements assessed in context with US state and federal regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e\u0026nbsp;Two US-based brands, \"MG\" and \"Hippotine\" pouches, were identified in August 2024, advertised to contain \"Imotine\"-trademarked 6MN. MG Pouches are marketed in four youth-appealing flavors. \"Hippotine\"-branded pouches are marketed in two flavors. 6MN contents ranged between 8mg - 25mg with almost identical ingredient lists otherwise. Products list extensive addiction and health warnings, including warnings not to operate vehicles. Vendors state that these are not a tobacco product, implicating that federal and state tobacco regulations do not apply.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially given the high 6MN contents that exceed nicotine contents in popular US-marketed oral nicotine pouch products. Legislators and regulators need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of tobacco flavor bans and other regulations.\u003c/p\u003e","manuscriptTitle":"Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-20 03:43:27","doi":"10.21203/rs.3.rs-5110349/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6674280f-b610-42e3-b954-1ceec1e82cab","owner":[],"postedDate":"September 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":37837189,"name":"Epidemiology"},{"id":37837190,"name":"Marketing"},{"id":37837191,"name":"Health Policy"}],"tags":[],"updatedAt":"2024-09-20T03:43:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-20 03:43:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5110349","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5110349","identity":"rs-5110349","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}