6-methyl nicotine is here

Did you know that a synthetic analog of nicotine has been developed and is on the market?

It’s called 6-methyl nicotine (6-MN).

Before we get into some of the more recent findings about 6-MN, it’s important to understand one specific term related to the research.

The term is “reactive oxygen species”, or ROS.

Here’s the basic description of ROS from Wiki, quoted, broken down as bullets:

“…reactive oxygen species (ROS) are highly reactive chemicals formed from oxygen, water, and hydrogen peroxide…
ROS are pervasive because they are readily produced from O₂, which is abundant.
ROS are important in many ways, both beneficial and otherwise.
ROS function as signals that turn on and off biological functions…
ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.”

With that out of the way, next we’ll briefly look at what became a 4-part series.

Initially, I simply posted a work titled “Nicotine”.
Part 2 was suggested in response to Part 1, and was titled “Vape”.
Part 3 was suggested in response to Part 2, and was titled “Pouch”.

Now, in this fourth and final installment, I’ll share some findings from four recent papers about the synthetic nicotine analog called “6-methyl nicotine”. I learned about this synthetic nicotine analog while reading for “Pouch”.

The first paper I’ll present discusses how the initial development of synthetic nicotine analogs including 6-MN was done back in the 1960’s.

The authors also review other nicotine analogs such as 2-MN, 4-MN, and 5-MN. In doing so they state…

“The commercial applications for neurologically active nicotine analogs that might have been in mind by the researchers and/or the sponsor may have included uses as: (1) substitutes for nicotine in consumer tobacco products; (2) therapeutic pharmaceuticals; and/or (3) insecticides…”

They discuss the advancement of technology from cigarettes to electronic nicotine delivery systems (ENDS), and then on to nicotine analogs, as follows:

“The commercial appearance of e-cigarettes (ENDS) in 2003 marked the end of the era of tobacco control and the beginning of an era of tobacco and nicotine control. Then, the appearance in 2023 of 6MN in commercial vaping systems began the current era, that of tobacco, nicotine, and nicotine analog control.”

Pankow, J.F., Luo, W., McWhirter, K.J. et al. Levels of the nicotine analog 6-methyl nicotine as a naturally formed tobacco alkaloid in tobacco and tobacco products. Sci Rep 15, 17945 (2025). https://doi.org/10.1038/s41598-025-01392-6

The second paper I’m sharing, from 2024, describes products containing 6-MN being introduced in Europe in 2019.

The authors state…

“A new nicotine delivery system in the form of tobacco‐free nicotine pouches was introduced in Europe in 2019.

These nicotine bags did not fall under the Tobacco Products Directive (TPD) II, which brought forward regulatory requirements for both cigarettes, related products, and e‐liquids.

As these pouches did not fall under the scope of the TPD, it was up to the member states to decide which action to be taken if any.

Some EU member states banned these nicotine pouches, while others put restrictions on the amount of nicotine, warning messages, and presentation and packaging of the product, and some member states did not take any action.

Early 2024, ‘NoNIC’ pouches, claiming to be tobacco‐ and nicotine‐free, became available on the European market.

These pouches are promoted online and clearly target a younger population with a youth‐appealing package design and enticing flavors.

Upon analysis…it was demonstrated that these pouches were indeed devoid of nicotine but contained the synthetic nicotine homolog 6‐methyl nicotine (6‐MN) and this up to 20 mg per pouch.

Nonetheless, a part of a likely unaware/misled young adult subpopulation has easy access to these products, containing a novel molecule for which limited to no clinical effects are known.”

Vanhee, C., Dill, M., Canfyn, M., Tuenter, E. and Barhdadi, S. (2024), The Emergence of a Novel Synthetic Nicotine Analog 6-Methyl Nicotine (6-MN) in Proclaimed Tobacco- and Nicotine-Free Pouches Available in Europe. Drug Testing and Analysis. https://doi.org/10.1002/dta.3841

The third paper is from 2025 and outlines some information about regulatory control and toxicity related to 6-MN.

The authors state…

“Nicotine-contained e-cigarettes (E-cigs) generate reactive oxygen species (ROS), volatile organic compounds, and heavy metals.

Inhalation toxicology studies suggest that exposure to these toxicants may adversely impact human health.

These findings led to the U.S. Food and Drug Administration’s (FDA) regulation of nicotine-containing E-cigs under the Tobacco Regulation Act (TRA) of 2020.

Manufacturers aiming to sell nicotine products in the U.S. must submit a Premarket Tobacco Product Application (PMTA) and obtain FDA approval before marketing their products. However, due to the lengthy PMTA process, some companies have exploited a loophole in the TRA (2020) by introducing nicotine analogs, such as 6-methyl nicotine (6-MN) into E-cig products.

6-MN is marketed as a ‘safer’ alternative to nicotine, offering comparable satisfaction despite not being derived from tobacco or nicotine. Nonetheless, its safety profiles are unknown.

We observed that thermal degradation of 6-MN in e-liquids significantly generated more ROS in the aerosols than nicotine.

6-MN-contained e-liquids significantly increased cytotoxicity and intracellular ROS induction in a dose-specific manner compared to nicotine.

Further, we observed that 6-MN (pure compound) transiently increased metabolic activity significantly at all doses tested compared to nicotine.

Given the potential risks associated with 6-MN, it cannot be deemed ‘safer’ than nicotine.

Therefore, further primary toxicological research is urgently needed to provide regulatory agencies with more robust data to implement regulations.”

Felix Effah, Yehao Sun, Alan Friedman, Irfan Rahman. Emerging nicotine analog 6-methyl nicotine increases reactive oxygen species in aerosols and cytotoxicity in human bronchial epithelial cells, Toxicology Letters, Volume 405, 2025, Pages 9-15, ISSN 0378-4274, https://doi.org/10.1016/j.toxlet.2025.01.007.

The final paper I’ll share is from 2025. It discusses a product that was introduced in 2023.

The authors state…

“The tobacco industry is known for constantly probing FDA’s regulatory limits.

In 2023, an e-cigarette product was introduced that, instead of nicotine, delivers a nicotine analogue, 6-methyl nicotine (6MN), claimed to be outside of FDA’s regulatory authority.

Pre-clinical studies demonstrated that 6MN is more potent than nicotine, raising concerns about increased addictiveness and toxicity.

We aimed to identify additional e-cigarette products containing 6MN, chemically analyze their 6MN contents for risk assessment, and test the toxicological properties of 6MN in bronchial epithelial cells.

Additional trademarks for 6MN were identified, including “Imotine”, “Nixotine”, “NoNic” and “SFN” (Substitute For Nicotine).

Between July – October 2024, four new product brands advertised to contain 6MN were identified, including three disposable e-cigarette brands, and one refill liquid brand.

Concentrations of 6MN measured in e-liquids diverged widely from concentrations listed on product labels.

6MN was more effective than nicotine at inducing cell death of BEAS-2B cells…

6MN also reduced oxygen consumption and other metabolic health parameters at lower concentrations than nicotine.

The number of US-marketed 6MN-containing e-cigarette brands and model varieties is increasing, suggesting confidence in the strategy to use nicotine analogues to bypass federal and state regulations that restrict tobacco product flavors.

Actual contents diverge strongly from label information, raising concerns about adverse effects and addictiveness.

6MN is more potent than nicotine at eliciting toxicological effects in human bronchoepithelial cells…

Nicotine analogues should be urgently addressed by lawmakers and regulators, and FDA should be granted the authority to regulate products containing them as tobacco products.”

S.E. Jordt, A. Caceres, P. Silinski, and S.V. Jabba. 6-methyl Nicotine in Electronic Cigarettes: Chemical Analysis and Toxicological Properties. Am J Respir Crit Care Med 2025; 211:A7552. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A7552

Personally, it’s interesting to me that we start with tobacco, move to nicotine vape, then on to the nicotine pouch, and eventually drift to synthetic nicotine analogs.

And all along we see a consistent theme of:

harmful (and unknown) ingredients,
marketing to children and youth,
avoiding regulation via innovation, and
what amounts to a long-term population-sized experiment.

And so, I wonder what the reader’s answer might be to the following question: “On a scale from 0 to 10 how important is it to treat tobacco use in a patient with a substance use disorder? And why?”