Alarm over the marketing of 6-methyl nicotine in disposable e-cigarettes

Figure 1: Chemical structures of (S)-nicotine (left), the main form of nicotine in tobacco, and (S)-6-methyl nicotine (right), marketed under the brand name Metatine, with a methyl substitution (blue) at position 6 of the pyridine ring (positions numbered in green). The red asterisk indicates the chiral centre of nicotine.[ii]

With 6-methyl nicotine (6-MN) we are dealing with a chemical substance developed in the laboratory, which is not nicotine in the strict sense of the term, but which has been constructed to imitate, or even reinforce, the psychoactive effects of nicotine.

Nicotine: Nicotine is a natural compound mainly found in tobacco plants. It is composed of two rings: a pyridine ring and a pyrrolidine ring. In the tobacco plant (Nicotiana tabacum), (S)-nicotine constitutes approximately 99% to 100% of the total nicotine. (R)-nicotine is either absent or present in negligible quantities (<1%).

6-Methyl Nicotine: 6-MN is a synthetic variant of nicotine where a methyl group is added to the 6-position of the pyridine ring of the nicotine molecule. This modification may influence how the molecule interacts with receptors and other biological targets. Like nicotine, 6-MN works by binding to nicotinic receptors in the human body. This interaction may be stronger, suggesting a greater addictive potential than nicotine. While one manufacturer-sponsored study claimed that 6-MN may be less addictive than nicotine,[iii] previous pharmacological studies have shown that 6-methyl nicotine is three times more potent in replacing [3H] nicotine in rat brain membranes and five times more potent in causing prostration behaviour.[iv] 6-MN is also always present in the form of salts, which facilitate the absorption of the substance by the brain.

For example, a concentration of 1mg/ml of 6-MN would produce an effect as satisfying as 3mg/ml of nicotine. 6-MN is also more toxic than nicotine. Studies in rats have shown that the median lethal dose (LD50), or the dose required to kill 50% of the test subjects, of 6-MN is up to three times lower than that of nicotine, indicating that 6-MN may be toxic at much lower doses.

6-MN is synthesised entirely in the laboratory from chemical compounds. Recent patents describe methods for synthesising 6-MN from petrochemical sources. Shenzhen Zinwi Biotech, a leading e-liquid manufacturer in China, holds one of these patents and sponsored a toxicology study at Guangdong Pharmaceutical University. The study found that 6-MN exhibits higher cytotoxicity than traditional nicotine in human bronchial epithelial cells, although it appears to have more moderate effects on proteins associated with lung cancer.[v] These findings are very concerning, especially coming from a study funded directly by the industry that markets the substance.

Another recent study, this time independent of the industry, draws explicitly more worrying conclusions regarding 6-MN. This study highlights the toxicological risks associated with 6-MN, which is increasingly used in e-cigarette products. The results show that 6-MN induces an increased production of reactive oxygen species (ROS) in the e-cigarette aerosol and inside cells, thereby increasing cytotoxicity in human bronchial epithelial cells compared to that of traditional nicotine. Flavoured e-liquids containing 6-MN showed a dose-dependent increase in cytotoxicity compared to nicotine. Furthermore, 6-MN as a pure compound significantly increased metabolic activity at all doses tested compared to nicotine. Thus, 6-MN cannot be considered in any case less dangerous (or “safer”) than nicotine. Furthermore, the study highlights potential gaps in current regulatory frameworks, which allow such products to be placed on the market without adequate safety assessment.[vi]

The first e-cigarettes with 6-MN appear to have been launched by Charlie's Holdings under the brand name Spree Bar. In response to questions from Reuters about 6-methyl nicotine and other nicotine alternatives, the US Food & Drug Administration (FDA) said in a statement:

"Although more research is needed, some emerging data show these nicotine analogs may be more potent than nicotine – which is already highly addictive, can alter adolescent brain development and have long-term effects on youth’s attention, learning, and memory."[vii]

A study of these products identified significant discrepancies between the reported and measured components of e-cigarette products containing nicotine alternatives. This discrepancy is misleading to consumers and raises concerns about manufacturing errors. 'SpreeBar' products also contained neotame, a high-intensity sweetener that is stable at high temperatures, likely increasing their appeal to youth and first-time users.[viii]

The Aroma King brand, which has several products containing 6-MN, manipulates the narrative to make people believe that this substance is not dangerous, when there is no scientific evidence to support this claim. We found information produced by Aroma King on the Finnish sales website Pussit.com. The website states that “The manufacture of synthetics, in this case, is a good thing because 6-methyl nicotine is not derived from tobacco or nicotine. It is therefore a compound that mimics the properties of natural nicotine, but reduces certain risks, such as carcinogenicity.” This claim is an absolute lie: just because a substance is synthesised in a laboratory does not mean that it is not dangerous. Furthermore, there is no scientific basis for claiming that it reduces the risk of cancer. Image 2 shows how Aroma King pretends to care about people's health by claiming without any scientific basis that 6-MN would have a significantly lower toxicity than nicotine, maintaining that this "innovative" product would be much safer for both older and young consumers! We do not have enough words to denounce such scientifically false and scandalous claims. It is obvious that Aroma King is targeting young people by encouraging them to consume its products without worry.

Public health authorities have paid little attention until recently to the risks of nicotine analogues. However, on 29 May 2024, a group of leading US public health and tobacco control organisations (including the American Cancer Society, the American Heart Association, and the American Lung Association) wrote an urgent letter to the US Food and Drug Administration (FDA) to denounce the risks associated with these substances.[x]

Nicotine analogues circumvent laws

Today, at least three major Chinese e-cigarette companies (Hangsen International Group, Zinwi Biotech, and Smoore International) are researching nicotine-like chemicals. Hangsen International Group and Zinwi Biotech are currently studying at least 10 nicotine analogues, while acknowledging that the health risks associated with these substances are not yet known.[xi]

A significant commercial advantage of 6-MN products is that they allow companies to circumvent regulations targeting nicotine.[xii] This situation is reminiscent of the ban on nicotine as a pesticide. In the United States, the majority of nicotine-based insecticides were banned in 2009, followed by the European Union in 2013. Following these bans, the industry developed a new class of products, neonicotinoids, some of which were in turn banned by the EU in 2018. Today, with increasing restrictions on nicotine use, including bans on products such as disposable e-cigarettes, the industry is seeking to develop new substances to circumvent these bans.

Swiss law and 6-methyl nicotine

Tobacco (intended for smoking, inhaling after heating, or snuffing), nicotine products with or without tobacco intended for oral use, as well as herbal smoking products, are now regulated in the Tobacco Products Act (art. 3 al. 1 LPTab) in effect since 1 October 2024. All e-cigarettes, whether or not they contain nicotine, also fall within the scope of this law (art. 3 let. f LPTab).

Plant-based products for heating, nicotine snuff products, and non-tobacco waterpipe products, comparable in contents or consumption methods to tobacco products, have been designated as tobacco-like products (art. 3 OPTab in connection with art. 4 LPTab). However, products intended for oral or nasal use, also comparable in their contents or methods of consumption to tobacco products, but containing neither tobacco nor nicotine, have been omitted from the scope of the law.

The concept of nicotine in the LPTab is not defined by the legislature, but clearly designates nicotine and its salts, extracted both naturally and obtained synthetically. A synthetic analogue of nicotine that is chemically distinct from nicotine and is neither composed of nicotine nor derived from nicotine[xiii], 6-methyl nicotine could therefore not be considered a form of nicotine within the meaning of the LPTab. It is only when the latter substance is consumed through e-cigarettes that the law could be applicable to it, because this method of consumption is always subject to the law, regardless of the presence or absence of nicotine in the product.

The consumption of 6-methyl nicotine via e-cigarettes would however not be affected by the quantity restrictions of the LPTab applicable to liquids, i.e. a maximum of 10ml for each refill or 2ml for each disposable e-cigarette and each single-use cartridge (art. 9 LPTab). These restrictions are expressly limited by law to liquids containing nicotine. The limit of the nicotine level contained in liquids of a maximum of 20mg/ml (art. 7 al. 2 & Annexe 2 LPTab) would not be applicable either.

Even more surprising, given its addictive potential, is that the ban on advertising (art. 18 ss. LPTab) and on the delivery to minors (art 23 LPTab) would also only apply to 6-methyl nicotine consumed through e-cigarettes, but not to other forms of consumption.

As explained above, oral or snuff products that do not contain tobacco or nicotine are not subject to the LPTab and, consequently, such products without traditional nicotine or tobacco but containing 6-methyl nicotine also do not fall within the scope of this legislation.

Paradoxically, these products, which are not subject to the Tobacco Products Act, are taxed as substitute products under the Tobacco Tax Act in the same way as manufactured tobacco (art. 3 OlTab in connection with art. 2 LTab). Disposable e-cigarettes are also taxed by the law, regardless of their nicotine content (art. 10 al. 1bis let. b LTab), whereas liquids for rechargeable e-cigarettes containing only 6-methyl nicotine would be excluded from the tax (art. 10 al. 1bis let. a LTab).

Unlike in Swiss legislation, the concept of nicotine defined in the EU Tobacco Products Directive 2014/40/EU (art. 2 let. 19) explicitly includes all nicotine alkaloids within the regulatory framework and therefore 6-methyl nicotine would be subject to it.[xiv] E-cigarettes imported into Switzerland under the Cassis de Dijon principle would therefore have to comply with the quantity and volume limits set by the EU. (The LPTab has taken up these same limits. See above).

These limits are set for nicotine based on the well-studied and therefore known addictive potential of this substance. The question arises as to the relevance of applying these same limits to 6-MN, whose addictive potential is unknown but could be even higher than that of nicotine.

Marketing these products which, due to their intended use, come into contact with the body, teeth, and mucous membranes, subjects them to the Foodstuffs Act (art. 2 & 5 let. b LDAl). According to this act, only safe products can be placed on the market (art. 15 al. 1 LDAl) and adding substances that have a pharmacological effect, such as nicotine and therefore also 6-methyl nicotine, is prohibited (art. 61 al. 2 ODAlOU).

Products intended for oral or nasal use containing 6-methyl nicotine, which are not subject to the tobacco product duty, would therefore in principle be prohibited by the law on foodstuffs and everyday objects. However, in accordance with the EU Cassis de Dijon principle, the import of these products is possible if they are legally marketed in a member state of the EU or the EEA. Exceptions to this are products on the Swiss Federal Council’s “negative list” of items that cannot be imported into Switzerland, despite the Cassis de Dijon principle (article 16 LETC); 6-méthyl-nicotine is not listed on the Council’s negative list (art 2 let. c ch. 13 & 14 OPPEtr).

Chemical substances and preparations may be placed on the market under the principle of self-control without prior administrative authorisation. Any new substance must be registered (art. 6 LChim), unless, among other exceptions, it is already listed in the EU REACH register or, among other exceptions, imported in quantities of less than one tonne per year per importer (art. 26 al. A let. c OChim).

6-methyl nicotine is registered only according to Regulation (CE) nº 1272/2008 on classification, labelling, and packaging of substances and mixtures (CLP) under its IUPAC nomenclature but it does not appear in the REACH register.

Clearly, 6-MN largely escapes the rules of consumer protection as well as those of youth protection currently anchored in Swiss legislation.

Market presence of products containing 6-methyl nicotine

Spree Bar-branded products containing 6-MN were first launched on the US market in 2023. Spree Bar’s website clearly claims that its products do not require FDA authorisation and can therefore be freely sold.[xv] Today, following the actions of the Trump administration, it is unclear whether an agency such as the FDA will still be able to regulate or control anything. The Spree Bar website also points out that, since Metatin is not subject to any taxation, its brand products are therefore much cheaper on the market. This reveals a clear strategy to circumvent nicotine restrictions, also complemented by an element that we do not hesitate to call tax evasion.

In 2024, 6-MN appeared massively on the European market, thanks to the company Aroma King, which registered the NoNic brand in the EU and the USA.[xvi] The presence of several products with 6-MN was also detected on the Australian market, which had managed to regulate the sale of e-cigarettes in an exemplary manner until now.[xvii] These products are now on sale on several websites, with the indication "0 mg (5% nicotine effect)" while on the product it is written "NoNic 20mg effect". Aroma King's NoNic disposable e-cigarettes also always exceed the European e-liquid volume limits of 2ml, such as the Aroma King NoNic Galaxy 15000 Puffs, which has an 18ml tank.

On the internet we find the promotion of the "New NoNic molecule" as a sales pitch. The indications "NoNic" or "0% nicotine" are misleading and deceptive. The product simply contains another chemical form of nicotine. This synthetic nicotine, also present in salt form, cannot be considered less addictive or less dangerous than traditional nicotine. As highlighted previously in our text, 6-MN and other nicotine analogues have not been scientifically studied for their health hazards and could present even more serious risks than traditional nicotine, both in their addiction potential and in their toxicity.

We also remind the reader that the capacity of a disposable system must be a maximum of 2ml of liquid, whether it contains nicotine or not. The 18ml disposable pod of the Aroma King NoNic Galaxy product can produce 15,000 puffs. Since 2014 we have been denouncing closed-system e-cigarettes with tanks larger than 2ml as being illegal in Switzerland, according to the European Directive of 2014.[xviii] This ban was taken up and confirmed by the new Swiss legislation, LPTab.[xix]

On the amazon.fr website we find another product, the Aroma King NoNic Galaxy 20mg effect 20000 Puffs. Like the previous one, it displays a warning on the front of the packaging, which leaves us perplexed, to say the least. Indeed, the warning first emphasises that "This product does not contain nicotine", but in a rather incoherent way goes on to indicate that "Nicotine is highly addictive".

As for Aroma King’s Swiss website, we have not yet found any products with 6-MN. However, products containing 6-MN can already be easily purchased on other European websites and we cannot exclude that they are already on sale on the Swiss market (because our association simply does not have the capacity to conduct in-depth monitoring of all products placed on the market). The Aroma King brand is well-established in Switzerland, with its own sales website, but also with products sold by Coop. We would also like to point out that these products are currently exempt from the new taxation on nicotine in e-cigarettes.

Nicotine pouches with 6-methyl nicotine

The market for nicotine pouches is booming, and some countries are also considering banning them. In the European Union, nicotine pouches have been widely used to circumvent the ban on snus, which is legal only in Sweden for historical reasons. Now, some European countries (such as Belgium) have already banned nicotine pouches or have announced their intention to do so (such as France and Poland). Thus, developing pouches containing nicotine analogues represents another way to circumvent legislation.

It is mainly the Aroma King brand that is returning to the forefront. Its pouches are presented as "NoNic", but it is claimed that NoNic is five times more powerful than traditional nicotine (20mg of NoNic is presented as the equivalent of 100mg of nicotine).

An English site presents the substance contained in Aroma King pouches as: “NoNic® is a non-toxic, non-addictive and non-psychoactive substance, and has an effect like nicotine. Patented substance.”[xxi] On another English site, PodPlug, Aroma King Super Kick NoNic cans are presented as: “Have the same nicotine buzz without the nicotine, this brand new revolutionary product is much less toxic, non-addictive and stimulates the same effect.”[xxii] Another page of the same site clearly states that “NoNicTM is a non-toxic, non-addictive and non-psychoactive substance, and has an effect just like nicotine. It can be used in both disposable e-cigarettes and nicotine pouches.”[xxiii] This site mentions as a reference an abstract presented at a conference. It should be noted that this is a conference organised annually by the tobacco industry, the Tobacco Science Research Conference.[xxiv] The abstract in question has never been published in a scientific publication, and there is no way to know who exactly funded this research. We consider the claims that 6-MN is not addictive or dangerous to be simply scientifically false and misleading.

At the moment, these products are mainly on sale on English or European websites at prices around 4 or 5 euros for a box of 25 pouches. It is possible to order them online without difficulty and have them delivered to Switzerland. We also see them in French TikTok videos that openly promote them as nicotine-free, non-addictive, and non-psychoactive products, presented as ideal before a football match or physical effort!

Note that Aroma King is a company created in 2019, based in Katowice, Poland, with a presence in more than 50 countries and a wide range of products, of which it claims to have sold more than 100 million units.[xxvi] The company seems to focus mainly on the European market, which is experiencing an annual growth of 30% in the nicotine pouch market. Aroma King has its own Swiss sales site, but these products are also distributed by Coop.

Continued presence of illegal products on the Swiss market

Throughout 2024, we repeatedly denounced the massive presence on the Swiss market of completely illegal e-cigarettes, as well as the inaction of public health authorities.[xxvii] We identified more than 100 websites selling disposable e-cigarettes exceeding the legal volumes of 2ml of e-liquids containing nicotine. Since the new LPTab legislation came into effect on 1 October 2024, it is clear that to date, most of these websites continue to sell products containing volumes of liquids far exceeding the legal standards.[xxviii] For example, the product "Aroma King 5500 Metallic Pink Orange Fizz 20mg" has a tank of 10ml of e-liquid, i.e. five times more than the legal standard of 2ml.

Numerous other websites continue to sell such products, such as WeVappy, which sells for example Puff Gear 10000 Strawberry Kiwi Vozol – 10000 Puffs – Disposable, for the price of CHF 24.90, with a 20ml tank, 10 times more than the legal volume of 2ml.[xxix]

If no effective measures are being taken to enforce a very clear law, how can we hope for action against nicotine analogues?

Conclusion: The need to ban all products containing nicotine analogues is urgent!

Products containing nicotine analogues, such as 6-MN, have been developed to circumvent existing legislation in various countries. Companies marketing these products often try to evade these regulations, mainly targeting young consumers with marketing strategies that falsely suggest that the absence of nicotine (NoNic) makes these products safe. The health risks and addictive potential of these analogues remain largely unknown, but it is plausible that they are at least as concerning, if not more so, than those associated with traditional nicotine. In the absence of robust scientific data on their addictive effects, particularly for young people, as well as on their health hazards, it is irresponsible to allow such products to be marketed. Companies should be required to prove the safety of these products before they are authorised to be sold on the market.

We call on the federal authorities to intervene urgently to clarify the situation regarding these substances and their uses, stipulating that their sale must be completely banned, in particular due to the principles of youth protection, and the precautionary principle in the face of the risks they present.