1 in 12 teens, young adults surveyed vape unregulated form of nicotine
- Among 1,760 adolescents and young adults (ages 14-25 years) surveyed, 20.1% recognized products with the synthetic nicotine analogue 6-methyl-nicotine, and 8.4% said they had ever used one.
- These prevalence levels were observed within less than a year since the predominant delivery system for 6-methyl-nicotine entered the U.S. market.
- Synthetic nicotine analogues are not regulated as tobacco and have little clinical evidence but some concerning animal data.
Unregulated synthetic nicotine analogues, namely 6-methyl-nicotine branded as Metatine in Spree Bar flavored vaping products, have gained "appreciable" awareness and youth among youth, the first prevalence survey showed.
In the survey of 1,760 people ages 14 to 25 years, 20.1% recognized 6-methyl-nicotine products, and 8.4% said they had ever used one, reported Adam M. Leventhal, PhD, of the Institute for Addiction Science at the University of Southern California (USC) in Los Angeles, and colleagues in Pediatrics.
"Notably, these prevalence levels were observed within less than a year since Spree Bar, a major delivery system for the nicotine analogue, 6-methyl-nicotine, entered the U.S. market in October 2023," the group wrote.
"These study findings emphasize the need for targeted regulatory activities addressing synthetic nicotine analogues to prevent uptake among young populations," Leventhal and colleagues concluded.
Synthetic nicotine analogues are marketed in flavored vaping products that anti-tobacco groups argue appeal to youth. While regulation of flavored vaping products in general has faced a tough battle, the synthetic nicotine analogues are bypassing U.S. tobacco regulatory safeguards altogether.
These products fall into what the researchers called a concerning gap both because they are exempt from premarket tobacco product application (PMTA) requirements and because of their pharmacologic impact.
While toxicity in humans remains unclear for these products that have recently entered the market, "animal studies indicate that 6-methyl-nicotine produces systemic toxicity, including neurotoxic effects, potentially at levels higher than nicotine," with methylation at points on the nicotine molecule that might enhance its addictive potential and biological effects.
"Indeed, the Spree Bar website claims that Metatine (i.e., 6-methyl-nicotine) provides 'pleasure and enjoyment,' 'combines well with flavors,' 'tastes great,' 'poses no additional risk,' and is 'half the price' and 'tax exempt,'" Leventhal's group pointed out.
The cross-sectional study used data from the USC Tobacco Center of Regulatory Science-Teen and Young Adult Tobacco Study, for which participants were recruited through the CINT online platform that connects researchers with opt-in panels of U.S. residents interested in participating in surveys for compensation.
From May to June 2024, 1,760 youth, ages 14 to 25 years, completed the survey across 48 states. Females accounted for 50.2% of the cohort, with 68.4% identifying as heterosexual.
The group was oversampled for tobacco use, with 1:1 sampling quotas by age group (55.6% adolescent vs young adult) and tobacco use (55.3% ever-users vs never-users). E-cigarette use was the most common tobacco product reported as having been used in the past 30 days, at 20.5%.
Current users of any tobacco product had higher awareness of nicotine analogue products compared with never-users in demographic covariate-adjusted models (28.9% vs 14.8%; adjusted OR 2.19, 95% CI 1.66-2.89). That nearly 15% of youth who had never used any tobacco products were "nonetheless aware of these nicotine analogue products ... suggests that the marketing reach of vaping products with nicotine analogues extends beyond traditional tobacco use groups," the researchers noted.
The only demographic factor associated with lower awareness was the "other" racial category that included non-Hispanic Asian, Native American, Middle Eastern, and other minority groups as compared with non-Hispanic white youth (8% vs 21.5%; aOR 0.33, 95% 0.19-0.60).
Current tobacco users also accounted for nearly all of the synthetic nicotine analogue use (20.2% vs 0.6% among never-users; aOR 37.74, 95% CI 15.22-93.60), particularly combustible cigarette users (25.2% vs 2.6%; aOR 12.91, 95% CI 7.85-21.25).
"This pattern reflects prior research indicating that multiple nicotine product use is increasingly prevalent among young people, a trend that carries substantial implications for public health," Leventhal and colleagues wrote, noting that the adolescent brain is particularly sensitive to the effects of intoxicating agents.
"Given that nicotine and nicotine analogues may interact through common neuropharmacological pathways, the long-term consequences of concurrent exposure are largely unknown and merit further investigation," they added.
Study limitations included the design that precluded temporal or causal conclusions, and possible reporting bias from the self-reported (albeit anonymous) sampling in a group not nationally representative.
"Updating federal policies to include nicotine analogues in the PMTA process would be impactful; however, states and localities can implement their measures in the meantime. For example, California recently enacted a law subjecting nicotine analogues to the same regulatory standards as other tobacco products," the researchers wrote. "Despite these efforts, federal action remains essential to ensure comprehensive regulation of synthetic nicotine analogue products."
Disclosures
The study was supported by the National Institute on Drug Abuse.
Leventhal and co-authors disclosed no relationships with industry.
Primary Source
Pediatrics
Source Reference: Sanchez LM, et al "Awareness and use of vaping products with a nicotine analogue among adolescents and young adults " Pediatrics 2025.
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