July 2026: Synthetic Cooling Agents in E-Cigarettes Actively Enhance Nicotine Reinforcement and Dopamine Signaling
A recently published study1 is challenging a foundational assumption in the Electronic Nicotine Delivery Systems (ENDS) market. Researchers have discovered that synthetic cooling agents – most notably WS-3 and WS-23 – do far more than simply smooth out the harsh physical sensation of high-dose nicotine. Instead, these chemicals act synergistically with nicotine at a neurobiological level, significantly enhancing mesolimbic dopamine signaling and increasing behavioral reinforcement.
This finding shifts synthetic coolants from simple sensory additives into active pharmacological modulators. The research arrives at a delicate moment for the vaping sector, which has relied heavily on “iced” formulations to drive consumer retention and navigate shifting global regulatory frameworks.
Over the past decade, manufacturers faced escalating regulatory restrictions on characterizing menthol/mint flavors. In response, formulation teams turned to synthetic cooling agents. Unlike traditional menthol, compounds like WS-3 and WS-23 trigger the cold-sensing TRPM8 receptors in the airway without introducing strong minty odors or distinct tastes.
This strategy served a dual commercial purpose. First, it effectively eliminated the unpleasant throat hit associated with high-strength nicotine salts, facilitating consumer adoption and higher consumption frequency. Second, it created a lucrative regulatory arbitrage opportunity. Brands could offer an “iced” sensory experience while remaining compliant with bans aimed strictly at “characterizing flavors.”
The new research demonstrates that this commercial strategy carries unintended neurobiological consequences. By analyzing brain chemistry and behavioral patterns during nicotine exposure, the study revealed that synthetic coolants directly influence the brain’s reward machinery:
– Amplified Dopamine Release: Co-administration of synthetic coolants with nicotine generates a markedly higher surge of dopamine within the mesolimbic pathway – the brain’s central reward circuit – compared to nicotine administered alone.
– Heightened Reinforcement: This neurochemical spike directly translates to stronger behavioral reinforcement, meaning subjects in pre-clinical models demonstrated a significantly higher drive to repeat nicotine-seeking behavior when synthetic coolants were present.
– Direct Neurobiological Impact: The amplified reward signal operates independently of olfactory or flavor conditioning. The cooling molecules physically alter the neurochemical response to nicotine rather than simply tricking the senses through pleasant taste associations.
The revelation that coolants boost nicotine’s reinforcing power significantly alters the risk profile for ENDS manufacturers. Regulatory agencies, including the U.S. Food and Drug Administration’s Center for Tobacco Products, are progressively shifting their evaluation frameworks away from simple flavor definitions and toward comprehensive abuse liability metrics.
With empirical evidence showing that WS-3 and WS-23 increase addiction potential, regulators could develop a mandate to expand prohibitions to non-nicotine sensory additives. Formulations heavily reliant on synthetic coolants could face heightened scrutiny during Premarket Tobacco Product Application (PMTA) reviews and an elevated risk of retroactive market withdrawals.
August 2025: Modification of vapes by the users is widespread in the U.S.
A 2025 study published in Scientific Reports2 examines how commonly users of electronic nicotine delivery systems (ENDS) in the U.S. modify their devices, the types of modifications they make, and their motivations. Using data from a nationally representative 2021 survey of 1,947 ENDS users across three age groups – youth (13–17 years), young adults (18–29 years), and older adults (30 years and older) – the research found that modifications are widespread and often risky, particularly among youth.
The study revealed that 84.3% of youth, 84.1% of young adults, and 76.9% of older adults had modified their devices in some way. Youth reported the highest average number of modifications at 9.0, compared to 6.6 for young adults and 5.0 for older adults. E-liquid modifications were the most prevalent type of alteration, with 68.1% of youth, 61.2% of young adults, and 48.7% of older adults reporting actions such as adding flavorings, mixing e-liquids, or even creating their own e-liquids. Coil modifications, such as cleaning or replacing the coil, were similarly common across all age groups, while battery modifications -arguably the most hazardous – were most prevalent among youth (58.3%), followed by young adults (44.8%) and older adults (36.2%). 40% of youth reported rewiring batteries themselves, a practice that significantly increases the risk of device malfunction, fire, or explosion.
Voltage and wattage adjustments were more common among adults, with over half reporting such modifications, while pod-related modifications – such as refilling pods not designed to be refillable – were more common among younger users. About one in five youth reported building ENDS devices from scratch, a rate significantly higher than among adults.
Users gave a range of reasons for modifying their devices. Enhancing flavor was consistently the most cited motivation, especially among youth, 90% of whom mentioned it when making their own e-liquids. Young people were also strongly influenced by social factors, such as peer behavior and online trends, while older users tended to emphasize cost-saving and increasing device longevity. Trying new things was a commonly shared reason across all groups.
The study also identified racial and ethnic disparities in modification behaviors. White non-Hispanic youth had the highest rates of e-liquid and coil modifications. Among adults, Black and Hispanic users were more likely to perform potentially dangerous modifications, such as wiring new batteries or adding cannabis to e-liquids. These findings suggest that both age and demographic factors influence not only the prevalence but also the nature of ENDS modifications.
Health risks associated with modifications could be significant. Youth in particular are engaging in behaviors not intended by manufacturers, such as altering voltage settings or adding unknown substances – including honey, fruit juice, cannabis, alcohol, and even cocaine – to e-liquids. These changes can increase exposure to harmful chemicals, raise the risk of acute intoxication or poisoning, and elevate the chance of mechanical failure.
The study concludes that the high rate of modifications among ENDS users should be factored into regulatory evaluation of ENDS products. The authors call for clearer product warnings, targeted educational campaigns, and policies that address both the technical and social drivers behind these practices. They also stress the need for further research into the frequency and regularity of such modifications and how regulations like flavor bans might influence user behavior.
June 2025: Elevated Toxic Element Emissions from Popular Disposable Vapes in the U.S.
Disposable vapes – single-use e-cigarette devices that have surged in popularity among adolescents and young adults- could pose unexpectedly serious toxicological risks due to metal emissions. In a recent study3 published by American Chemical Society (ACS), three leading disposable vape brands – ELF Bar, Flum Pebble, and Esco Bar – were subjected to metal-content analysis over their full lifespans (up to 1,500 simulated puffs). Analytical methods revealed that all devices emitted nickel (Ni), chromium (Cr), antimony (Sb), and notably high levels of lead (Pb). Lead and nickel levels escalated dramatically during use, often surpassing concentrations observed in conventional refillable e-cigarettes by as much as 100 folds. In Esco Bar devices, lead concentrations reached up to 175,000 µg/kg – comparable to or exceeding the daily lead exposure from smoking 20 packs of cigarettes.
Component-level investigations determined the origins of these toxic metals. Lead and nickel were traced to leaded bronze alloys in non-heating internal parts, while nickel also originated from the heating coils themselves. Antimony, initially present in unused e-liquid, lacked a clearly identified hardware source. Oxidation-state analysis showed that chromium was exclusively in the less-harmful Cr(III) state; however, antimony was present in both Sb(V) and carcinogenic Sb(III) forms. These findings underscore that toxic substances are introduced both from constituent materials and chemical reactions occurring during typical use.
Quantitative risk assessments compared the measured aerosol concentrations to established toxicity benchmarks. Nickel and Sb(III) in aerosols from several devices exceeded cancer risk thresholds; respiratory and neurological safety limits were surpassed for nickel and lead in four devices by up to ninefolds. Lead emissions from a single disposable device during a day’s use rivaled those from nearly 20 packs of traditional cigarettes – a stark indication of elevated toxic burden. The investigation spanned new, mid-life, and end-of-life product stages, demonstrating that metal emissions increased significantly with continued use, thereby intensifying health risks over time.
Despite many brands being unapproved by the US FDA, disposable e-cigarettes are commercially ubiquitous, especially among youth, who are especially vulnerable to neurotoxic and carcinogenic exposures. The use of leaded materials and insufficient manufacturing oversight highlights a pressing regulatory gap. Authors emphasize the urgent need for stronger enforcement, noting that toxic exposures from disposables may even surpass those associated with traditional cigarettes and recommend broadening the scope of future studies to encompass a wider range of brands and flavors, investigating long-term usage patterns, and assessing in vivo biological impacts, to inform policy and protect public health.
Meanwhile, popular vape brands, Elf Bar and Lost Mary, stated that they recognize the role of alloy composition in the thermal stability of heating coils, which influences aerosol safety. They conducted in-depth research on how various metal ratios affect the performance of ceramic coils and their research suggests that an optimised nickel-chromium-iron alloy ratio in coils extends their lifespan and lowers heavy metal levels in vape aerossol. The findings also support improvements in ceramic coil composition, helping minimise users’ exposure to potentially harmful byproducts.
June 2025: A vast majority of popular disposable vapes in the U.S. contain neotame, a potent, unregulated artificial sweetener
According to a recent study conducted by the Duke University researchers4, a vast majority of popular disposable vapes in the U.S. contain a high-intensity, unregulated artificial sweetener that may enhance the appeal to youth and first-time users. The additive neotame is 7,000-13,000 times sweeter than sucrose (table sugar) and differs from the better-known aspartame in one molecular feature. Neotame is often used in vapes that come in fruity, candy and cool mint flavors.
Researchers selected 55 popular disposable vapes based on the 2024 U.S. market surveys. The selection included the popular brands like Elfbar, Geekbar, Mr. Fog and Breeze (27 products) and a range of products that contain no nicotine (8 products) or synthetic nicotine analog, 6-methylnicotine (20 products). For comparison, 11 FDA-authorized e-cigarette products, 2 JUUL products and Mentos mint candy product were also analyzed. The analysis employed Liquid Chromatography–Mass Spectrometry (LC-MS) to detect and quantify neotame, nicotine, 6-methyl nicotine, and cooling compounds such as menthol, WS-3 and WS-23.
Key study findings are:
– Neotame Detection: All 55 popular disposable vapes (nicotine, zero-nicotine, or nicotine analog) contained neotame, with an average neotame content that was almost five times higher than in a Mentos mint candy. Disposable vapes with nicotine analog, 6-methylnicotine, contained the highest average neotame content. In contrast, neotame was not detected in any of the 13 FDA-approved e-cigarette products or in JUUL products.
– Cooling Agents: The synthetic coolant WS-23 was present in the majority of tested products, while menthol and WS-3 were less commonly found.
– Nicotine Analogs: Notably, in certain products like “SpreeBar,” the actual concentration of 6-methyl nicotine was significantly lower than what was indicated on the label. No nicotine was detected in zero-nicotine or nicotine analog products.
The widespread presence of neotame in disposable e-vapes raises several concerns. The combination of high-intensity sweeteners like neotame with cooling agents and sweet flavors (e.g., fruit, candy) may enhance the appeal of these products to younger users, potentially increasing the risk of initiation and continued use. Moreover, neotame’s effects when inhaled, especially when heated and vaporized by an e-cigarette, are not well understood. Further research is necessary to evaluate the potential toxicological impacts of inhaling neotame and its degradation products.
The study underscores the high prevalence of neotame in U.S.-marketed disposable vapes, particularly those not approved by the FDA. The findings suggest a need for an increased FDA scrunity on neotame and comprehensive regulatory evaluation of such additives in vapes, especially considering their potential appeal to youth and unknown health effects upon inhalation.
Meanwhile, popular vape brands, Elf Bar and Lost Mary, stated that they have conducted extensive research on sweeteners and identified neotame as a safer alternative to sucralose. Their tests show that e-liquid samples with neotame have lower heavy metal content, generate fewer heavy metals in vape aeresol, and demonstrate reduced cellular toxicity compared to those with sucralose. Based on these findings, Elf Bar and Lost Mary are minimising the use of sucralose and other unvalidated sweeteners.
February 2025: UK will investigate the health impact of vaping on children
The UK Government announced a comprehensive initiative to investigate the long-term health effects of vaping on children aged 8 to 18. This decade-long study, with a budget of £62 million, aims to address the rising trend of vaping among young individuals and its potential health implications.
– Study Scope and Objectives: The research will monitor 100,000 participants over ten years, collecting data on their behavior, biological changes, and health records. The primary goal is to gain a detailed understanding of how vaping affects the developing bodies and minds of children.
– Legislative Measures: In tandem with the study, the government plans to implement a ban on disposable vapes starting in June 2025. Additionally, the proposed Tobacco and Vapes Bill seeks to restrict flavors and packaging designs that appeal to children, aiming to curb the attractiveness of vaping products to the youth. For further details: Disposable E-cigarettes.
– Public Health Concerns: Health experts have raised alarms about the potential risks of vaping on young individuals. Airway inflammation, exacerbation of asthmatic conditions and adverse effects on brain development are most commonly highlighted concerns.
– Regulatory Actions: Unlike traditional cigarettes, which are heavily taxed and regulated, vapes have not been subject to similar ‘sin taxes’ and often feature colorful designs and enticing flavors. To address this, the Government plans to introduce a flat-rate duty on vaping liquids starting as of October 2025. A nationwide campaign targeting youth will also be launched, primarily utilizing social media platforms and influencers to disseminate information about the potential risks associated with vaping.
Trends in Long-term vaping among adults in England, 2013-2023
According to the findings of a study based the data drawn from a monthly cross-sectional survey of a representative sample of adults in England5, the prevalence of long-term vaping (i.e. currently vaping for a period of more than six months) increased non-linearly among adults in England during 2013-2023. The proportion of long-term vapers among adults increased from 1.3% in October 2013 to 10.0% in October 2023, with a particularly pronounced rise from 2021. According to The Office for National Statistics (ONS), 12.7% of adults (people aged 18 years and over) smoke in England.
Growth is especially more pronounced in young adults (prevalence reaching 22.7% among 18-year-olds vs. 4.3% among 65-year-olds) and among people with a history of regular smoking: up from 4.8% (in October 2013) to 23.1% (in October 2023) among current smokers, from 5.7% to 36.1% among who recently quit smoking and from 1.4% to 16.2% among ex-smokers. An increase also occurred among people who never regularly smoked, especially the young adults: prevalence reaching 16.1% among 18-year-olds who had never regularly smoked vs. 3.0% among all never smokers.
Much of the growth occurred from 2021, coinciding with the rise in popularity of disposable e-cigarettes. Half of long-term vapers now mainly or exclusively use disposable devices. Between October 2013 and March 2021, most long-term vapers used refillable e-cigarettes (2.5% of adults) and a few (0.1% of adults) used disposable devices. However, prevalence of long-term vaping using disposable devices subsequently rose rapidly and, as of October 2023, similar proportions of adults mainly or exclusively used disposable (4.9%) and refillable (4.6%) devices.
Trends in Vaping & Smoking in England following the rise of Disposable Vapes
According to the findings of a study based on nationally-representative monthly survey data (July 2016 – May 2023)6, post-disposables, the overall prevalence of inhaled nicotine use (smoking & vaping combined) in England increased across all age groups. Pre-disposables (before June 2021), the prevalence of inhaled nicotine use had been stable or declining.
Following the launch of modern disposable vapes (i.e. effective – in terms of nicotine delivery, affordable, convenient, concealable), use of e-cigarettes increased sharply in England – with the most pronounced rise observed among the young adults. Vaping prevalence among the 18-24-year-olds increased from 9% in May 2021 to 29% in May 2023 (from 10% to 17% for the 25-44-year-olds and from 5% to 6% for those aged 45 or older).
Despite a tripling in vaping among young adults, smoking continued to decline at the same rate pre- and post-disposables. As a result, downward trends in inhaled nicotine use have reversed – with prevalence of inhaled nicotine use being up from 28% in May 2021 to 35% in May 2023 among the 18-24-year-olds.
Researchers conclude that prior to June 2021, UK’s lenient approach towards e-cigarettes seemed to encourage adults to switch from smoking to vaping while avoiding excessive nicotine use among young people. However, launch of disposables (e.g. Elf Bar, Puff Bar, Lost Mary) resulted in the rapid increase of vaping prevalence among young adults, including among those who have never regularly smoked cigarettes.
Recall: Disposable vapes will be banned in the UK from April 2025. For further details, refer to Regulation: E-cigarettes.
Study Links E-Cigarette Use with Higher Risk of Heart Failure
According to the findings of a large study presented at the American College of Cardiology’s Annual Scientific Session7, people who use e-cigarettes are 19% more likely to develop heart failure compared with those who have never used them. Breaking the data down by type of heart failure, risk increase was significant for heart muscle becoming stiff and failing to properly fill with blood between contractions.
For the study, the researchers used data from a large national study of US adults to analyze associations between e-cigarette use and new diagnoses of heart failure in 175,667 study participants (an average age of 52 years and 60.5% female). Of this sample, 3,242 participants developed heart failure within a median follow-up time of 45 months. While calculating the heart failure risk increase, researchers accounted for a variety of demographic factors (age, sex), socioeconomic factors, other heart disease risk factors and participants’ substance use history (alcohol and tobacco products).
The findings are claimed to be in line with previous studies conducted in animals (i.e. e-cigarette use affecting the heart in ways that are relevant to the heart changes involved in heart failure). Other human studies to date have also shown links between e-cigarette use and some risk factors associated with developing heart failure – however, coming short of establishing a direct connection between e-cigarette use and heart failure (allegedly, due to the study design and sample size limitations).
Trends in Harm Perceptions of E-Cigarettes
University College London researchers examined how the harm perceptions of e-cigarettes (compared with cigarettes) have evolved since 2014 among the adult smokers in England8. They found that harm perceptions of e-cigarettes have worsened substantially over the last decade: the proportion of adult smokers, who believed e-cigarettes were less harmful than cigarettes, declined from 44.4% in Q4 2014 to 26.7% in Q2 2023. In the same period, the proportion, who thought e-cigarettes were more harmful, doubled to 23.3% (- the weight of “equally harmful” also increased slightly to 33.7%). Thereby, majority of the adult smokers (57%) in England now believe that e-cigarettes are equally or more harmful than cigarettes.
The evolution of perception over time was nonlinear. The timing of the two most notable changes in harm perceptions coincided with the EVALI outbreak in 2019 (short-lived, returning to pre-2019 levels by the end of 2020) and the recent increase in youth vaping in England since 2021.
Researchers observe that public health statements and media reports have often overstated the potential risks of e-cigarettes – resulting in substantial misperceptions about the harms of vaping (compared with smoking). They underscore the need to clearly communicate the risks so that adult smokers can make informed choices about the nicotine products.
In the UK, National Health Service (NHS) lists e-cigarettes as a “Stop Smoking Treatment”. To read more: Smoking Cessation Products
References:
- https://www.nature.com/articles/s41386-026-02485-0 ↩︎
- https://www.nature.com/articles/s41598-025-08722-8 ↩︎
- https://pubs.acs.org/doi/full/10.1021/acscentsci.5c00641 ↩︎
- https://www.researchsquare.com/article/rs-6074654/v1 ↩︎
- https://www.bmj.com/content/386/bmj-2023-079016 ↩︎
- https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00091-7/fulltext ↩︎
- https://www.acc.org/About-ACC/Press-Releases/2024/04/01/21/51/study-links-e-cigarette-use-with-higher-risk-of-heart-failure ↩︎
- Trends in Harm Perceptions of E-Cigarettes vs Cigarettes Among Adults Who Smoke in England, 2014-2023 | Public Health | JAMA Network Open | JAMA Network ↩︎
