Synthetic Nicotine: What You Need to Know

At eJuices.com, we have no interest in selling our products to adults who do not currently vape or use traditional nicotine products. We also do our utmost to combat underage vaping. We use cutting-edge age verification software and adult signature required upon delivery. Our goal is to help traditional nicotine users make the switch to vaping and to help vapers reduce their nicotine intake with the eventual goal of a vaping free lifestyle.

To achieve this end, we sell nicotine e-liquids and the hardware used to vape these e-liquids. Nicotine is an addictive chemical. Nicotine is the primary active ingredient in combustible nicotine products. But it is the act of burning tobacco that is responsible for litany of health issues associated with traditional nicotine ingestion methods. 

Former-FDA commissioner Scott Gottlieb, no ally of the independent vaping industry, discussed this paradox in a September 2018 press release.  

“What primarily causes death and disease from tobacco use isn’t the nicotine in these products. It’s the act of lighting tobacco on fire to free that drug for inhalation.

While it’s the addiction to nicotine that keeps people smoking, it’s primarily the combustion, which releases thousands of harmful constituents into the body at dangerous levels, that kills people.”

-Former FDA Commissioner Scott Gottlieb

Tobacco-Derived Nicotine

The FDA’s own words establish that combustible tobacco, rather than nicotine, is the biggest risk. But is it possible to separate nicotine from tobacco? On one side, tobacco’s appeal is largely linked to the nicotine to it contains. But there is a flipside to the coin: Not all nicotine comes from tobacco.

For vapers, this is more than just an issue of semantics and sophistry. Most adult vapers are former traditional nicotine ingestion users and loathe to put any more money into the hands of Big Tobacco. Yet as their name suggests, Big Tobacco is responsible for almost all the tobacco sold commercially.

Until recently, vape juices used tobacco-derived nicotine grown by a core of companies  viewed as a scourge on the landscape by the average American. Not only does tobacco-derived nicotine put money in the pockets of the tobacco industry but it supports wide scale industrial agriculture than has an enormous environmental footprint. 

Thanks to technological breakthroughs by Next Generation Labs and other manufacturers, affordable nicotine free from tobacco is now available for use in vape juice. The technology to manufacture synthetic nicotine has been available for decades but patented breakthroughs have made it a viable and affordable option for most e-juice companies. 

What is Nicotine?

In nature, nicotine is found in members of the nightshade family. Due to selective breeding and natural botanical attributes, it is found in by far the highest concentrations in the tobacco plant. But nicotine is also present in other nightshades such as tomatoes, potatoes, green peppers, cocoa plants, and eggplants.

Tobacco is the only nightshade plant with enough nicotine (5% to 7%) in its leaves for commercial nicotine production. But it has been controversial since a cancer study in 1950 linked its consumption in traditional nicotine ingestion products (primarily combustible nicotine products) to lung cancer fatalities. The grim discovery led to the rise of government-sponsored campaigns aimed at reducing smoking rates and the deaths caused by smoking.

Nicotine is an alkaloid. This word may look scary, but this simply means it is a nitrogenous compound of organic plant origin that interacts physiologically with humans. Okay. That may sound a bit wonkish too.

Alkaloids can be found in quinine which is a common treatment for malaria. Atropine, which is used in such varied medical uses as treating low heart rate and mushroom poisoning, is another alkaloid. The pesticide strychnine is an alkaloid and so is morphine.

So why are people consuming nicotine? Once consumed it is addictive, but what is the reason for initiation? Peer pressure must play a role. Most traditional nicotine ingestion users begin before the age of 21. This is one reason why we feel the Tobacco-21 Laws were the best method of combating underage vaping.

Just as importantly, nicotine is viewed as an anxiolytic drug. While it can be argued that nicotine is a terrible anxiolytic and actually fuels anxiety, this is a major reason that people take up combustable nicotine usage.  Nicotine is also a stimulant. Even in an age where smoking is understood and justly criticized for its hazards, the number of butts littering the gutter outside of bars is proof of this appeal.

Vaping Destroys Nicotine Replacement Therapy in NEJM Study

Researchers have established that nicotine in its pure alkaloid form is non-carcinogenic. A study published on Cancer.org found chemical compounds in the tobacco leaf, additives and chemicals formed during the combustion process are the real culprits. 

In the first decade of this century, nicotine vaporization via e-cigarettes and vape devices emerged as an alternative to combustible nicotine products. Smoking rates have subsequently declined, although in the US we are forbidden from drawing any conclusions on this front. 

This is not the case everywhere. In a study conducted in the UK, vaping easily outperformed nicotine replacement therapy. This was not some bunk science like the Stanton Glantz’s retracted study that linked vaping and heart attacks. This research was published in a gold-standard, peer reviewed journal. It was not a letter to the editor, but the primary feature in the New England Journal of Medicine study.

Prescription Vapes in UK

In the United Kingdom, the National Health Service (NHS), hosts a website domain Using E-Cigarettes to Stop Smoking.  They have also started a program where vape juices and devices are covered in their national prescription plan. This is no small deal. The wealthy have largely ceased using traditional nicotine ingestion products and did so two decades ago. Most of these users are from marginalized and underrepresented groups. It is from these groups that the majority of vapes emerge. The NHS concluded that covering the expense of vaping will save the country money. 

Public Health England, an executive agency in the UK’s Department of Health and Social Care, views vaping as being 95 percent less harmful than other traditional nicotine ingestion products.

Keep in mind the NHS has skin in the game. They are funded by taxpayers and do not cover treatments willy-nilly. In fact, their standards of care are extremely exacting. Herbal medicine, chiropractic care, health supplements and homeopathy have long since been axed from their coverage plans. This occurred despite these treatments being very popular with the wealthiest and most influential Britons. 

Even the London Fire Brigade has gotten in on the action. They have endorsed e-cigs as an alternative to combustible nicotine products after confirming that vaping prevents house fires. The UK has outperformed EU countries in smoking cessation. They credit their scientific based approach to e-cigarettes and argue that countless lives could be saved if other countries were willing to follow their lead. It remains to be seen if the US will ever follow suit. But the numbers suggest that marginalized traditional nicotine users would benefit the most from an about-face.

US Vape Regulations

By using taxpayer dollars to support vaping, underwriting the vaping purchases of the most vulnerable and encouraging traditional nicotine users to switch to e-cigarettes, the UK has adopted an approach that is the opposite of the United States and our puritanical policies. Total nicotine abstinence is considered the gold-standard. Unlike alcohol, which kills 3000 minors annually and sends 130,000 to the emergency room according to the CDC, nicotine is simply not popular with the wealthiest Americans who wield the power 

The hundreds of millions of dollars dedicated by Michael Bloomberg to eradicate vaping has cost adult vapers and traditional nicotine users access to the flavors and ash-free nicotine alternatives they prefer. 

The Food and Drug Authority (FDA) has classified tobacco-extracted nicotine as a tobacco product. This is why the regulation of vapes falls under the purview of the Center for Tobacco Products (CTP).

Unlike the UK where vaping is viewed as an alternative to traditional nicotine ingestion methods, for all intents and purposes vaping is considered that way in America and regulated as such.

What is Synthetic Nicotine?

Hopefully the information above clarifies and demystifies nicotine a bit. It is still an addictive but context, especially regarding vaping versus other methods, is crucial.

As the name implies, synthetic nicotine is manufactured from starter materials in a laboratory setting and does not rely on any part of the tobacco plant.

Synthetic nicotine is not merely mimicking the effect of the nicotine found in tobacco. It is more than just chemically similar. Synthetic nicotine is molecularly identical to the nicotine found in nature; 10 carbon atoms, 14 nitrogen atoms, and two nitrogen atoms (C₁₀H₁₄N₂).

It attaches to the body's nicotinic receptors exactly as plant-based nicotine would.

The molecular formula for nicotine is C10 H14 N2. It doesn’t matter if it is in Grandma’s Pall Malls, extracted from a tomato or made in a factory in Germany, the active nicotine molecule remains unchanged.

S-Isomer Nicotine

Nicotine is chiral molecule, meaning that it is not superimposable as a mirror image. There are two variations of the nicotine molecule: S-isomer and an R-isomer. In plant nicotine, R-isomer is only present in small quantities. Due to the way synthetic nicotine is manufactured, it is much cheaper to manufacture nicotine that is 50 percent R-isomer and 50 percent S-isomer.

The molecular formula may remain the same, but S-Isomer and R-Isomer have totally different biological effects. The R-isomer occurs in small amounts in whole leaf tobacco and is inert. S-Isomer has the biological effects associated with nicotine consumption.

As R-isomer is viewed as biologically inert, it takes twice the volume of a nicotine which is half R and half S-isomer to match the potency of pure S-Isomer.

The leading producer of pure S-Isomer is a Germany company: Contraf-Nicotex-Tobacco (CNT). Their spokesperson and VP Torsten Siemen takes a dim view of synthetic nicotine that contains R-Isomer: “We think R-S nicotine, which contains a significant amount of R nicotine, can only be considered to be an intermediate, which requires further purification to the S form. For these reasons, CNT does not sell R-S nicotine…In the best case, the same quantity of R-S nicotine can be considered to be only 50 percent effective.”

R-Isomer Nicotine

Before dismissing R-isomer nicotine as a waste product, it is worth considering the informed views of Next Generation Labs (NGL) founding member Ron Tully. NGL is the leading producer of non-tobacco nicotine currently found in vape juices. Their product, Tobacco Free Nicotine (TFN), largely dominates the US market.

“Nicotine has been studied extensively in its naturally derived tobacco form, which includes the naturally occurring S and R isomers, which are metabolized in the consumption of current cigarette, vape and smokeless tobacco products. There is nothing to indicate that the R isomer is anything other than a positive attribute to the nicotine molecule.”

A July 2021 press release by Next Generation Labs announced a had been granted patent for the use of TFN Combinational R- and S-Isomer synthetic nicotine in tobacco cessation products. In this release, NGL elaborated on their vision of a future that heavily features R-isomer nicotine. 

“Next Generation Labs believes future combinational R- and S-isomer nicotine formulations may prove to be less addictive than natural or biosimilar standalone S-isomer nicotine and could potentially help achieve the broader public health goal of providing adult consumers with a satisfying, but non-addictive form of nicotine to replace current products. These new variable isomeric ratios of synthetic nicotine products may ultimately assist adults in quitting or reducing their overall dependence on current tobacco, vape and nicotine products.”

“We are at an early stage in the evolution of isomeric nicotine and its utility. NGL is trying to ensure that companies have the option based on their evaluation of the utility and safety of synthetic nicotine in their products.”

Manufacturing Tobacco Free Nicotine

Without getting too far in the weeds, we have now covered how nicotine is consumed, how it is treated in the US and UK, and how tobacco-derived and non-tobacco nicotine are the same molecule. We learned that the nicotine molecule has two isomers. These two molecules,  S-nicotine and R-nicotine, are nearly identical chemically but that the biological impact of nicotine is attributed to the S-Isomer.

Despite tobacco nicotine containing mostly S-isomer nicotine, the first stage of the synthetic nicotine manufacturing process creates an equal percentage S and R-Isomer nicotine. This leaves two options, remove all the R-Isomer so that the potency by volume is the same as tobacco-derived nicotine or to use a greater amount of the R/S-Isomer nicotine to achieve the same potency. NGL provides a third method where some of the R-Isomer nicotine remains in the formulation.

There is competition in the synthetic nicotine marker. Not surprisingly, the German company that makes pure S-isomer nicotine is quick to claim that less expensive products with R-isomer are garbage. And the leading producer of S and R-Isomer nicotine is just as quick to counter this point.

The trade secrets behind the actual creation of synthetic nicotine are closely guarded. If you have any interest in completing the deep-dive, here is the patent for the manufacturing of S-isomer synthetic nicotine.

This document mostly covers that the end-product is racemic. Racemic just means that equal amounts of the left and right hand molecule are manufactured, i.e., R- and S-Isomer. This imbalance is resolved through use of catalysts to separate a racemic mixture into two individual enantiomers, each in its purest form.

All of this is standard procedure in a branch of chemistry called stereochemistry that focuses on molecular structure and atom arrangement. What you will not find in this patent are the specific raw materials and processes used to create synthetic nicotine in the first place.

Tobacco-Derived Nicotine Production

If the idea of laboratory and synthetic molecules seems a bit off-putting, it is worthy considering how the tobacco-derived nicotine found in your vape juice is made. Keeping in mind that the actual S-Isomer heavy nicotine blend is bioidentical. Hopefully, this information will help illustrate the “appeal to nature” fallacy. The earth is filled with very dangerous natural substances and very useful synthetic ones. It is the dose that makes the poison.

Industrial scale cultivation of tobacco requires considerable energy inputs and acreage. Pesticides, fossil fuels, fertilizer run-off and all manner of other concerns are closely tied to the cultivation of the tobacco plant.

Once the tobacco is harvested, the leaves are either chopped fresh or cured. Flue-cured tobacco is one of the traditional methods of tobacco processing. Cured tobaccos are sweeter, less caustic and usually associated with Virginia or North Carolina. Rather than some rustic shed, Big Tobacco is curing leaves in warehouse sized facilities. 

Once cured, tobacco leaves are processed with an organic solvent such as ethanol, water, or a petroleum products like petroleum ether. Such organic extraction solvents soak up the alkaloid molecules from tobacco leaves. The potency of the nicotine distilled from the tobacco leaves depends on the duration of the process and the solvent used.

Once the extraction step is complete, the resulting alkaloid solution undergoes distillation to remove all extraction solvent residue. The resulting distillate is pharmaceutical-grade nicotine, which is 99.9% pure.

In a second method,  water-diluted mineral acid can replace distillation. This aqueous mineral acid forces the alkaloid salt and the acid to form chemical bonds. The result is a residue that separates itself from the impurities present in the organic solution.

Adding a base like ammonia into the alkaloid salt solution causes the mineral acid to separate from the alkaloid and bind to the base in a neutralization reaction. Finally, a simple evaporation procedure results in the formation of a pure alkaloid. 

Clearly, neither the manufacturing of synthetic nicotine nor the extraction of purified nicotine from the tobacco plant is a DIY project.

Product Purity

S-nicotine is the dominant alkaloid in tobacco leaves, the plant contains other minor alkaloids including, anabasine, anatabine, and nornicotine.  These alkaloids may bypass the nicotine purification processes highlighted above and make it to the final pharmaceutical-grade nicotine extract.

The possibility that minute quantities of tobacco alkaloids exist in pharmaceutical-grade tobacco-based nicotine explains why it is 99.9% pure. However, most of these minor alkaloids mimic nicotine's effects on the body and are unlikely to alter tobacco-based nicotine's effects in any way.

On the other hand, synthetic nicotine contains nothing but pure S-nicotine molecules; hence it is 100% pure. Tobacco Free Nicotine (TFN) by Next Generation Labs contains R-isomer nicotine due to the racemic manufacturing processes but not the other alkaloid materials associated with the tobacco plant.

Vape juices made with TFN or synthetic nicotine may have a slightly clearer appearance compared to the dark tint found in more potent tobacco-derived nicotine formulas.

Synthetic Nicotine Flavor

TFN and synthetic nicotine have a more neutral flavor profile as well. This makes them ideal for vape juices. Tobacco has a distinct flavor and aroma that are not entirely wiped from the slate during the process that extracts nicotine from the leaves.

In contrast, synthetic nicotine is 100 percent flavorless and odorless. This is great news for adult vapers. Most adult vapers prefer fruit and beverage vape flavors over tobacco. This was demonstrated conclusively in a study by Dr. Farsalino.

There are many reasons for this. The obvious one should be mentioned first. Who does not prefer delicious flavors? Tobacco is a vehicle for nicotine that traditional users have grown accustomed to. When attempting to transition from combustible nicotine products to electronic cigarettes, it makes sense not to embrace flavors that remind you of smoking.

TFN and synthetic nicotine are better platforms for the flavors that adult vapers love. The nostalgic 1980s flavors which dominate the vaping landscape such as blue raspberry, never have tasted better.

Salt Nicotine Juice

There is no better time than now to briefly address nicotine salts. Salt nic juices and regular freebase e-juices can be made from tobacco-derived and synthetic nicotine.

Nic salts are the potent e-juices found in disposable vapes, refillable vape pods and sold in 30ml bottles for use in a refillable vape pod kit.

Nicotine salts are manufactured from the regular nicotine (freebase), which can come from either tobacco or non-tobacco sources.

Regular nicotine has a high-pH level. This makes no difference in low-potency max-VG juices but begins to make itself known with harshness when the nicotine strength rises above 12 to 18mg.

Max-VG juices, vaped in powerful devices, are consumed in such large vapor clouds that the lower strength does not mean an unsatisfying final product. There is no reason less potent nic salt formulas could not be manufactured. Apart from crossing the blood brain barrier more readily, it is still just nicotine.

But freebase nicotine is cheaper. Except for TruNic, One Hit Wonder and a couple of other vape juice companies, the demarcation line is very clear: salt nic juices have high concentrations of nicotine. Freebase nicotine is used in less potent e-liquids.

The reason for this line in the sand is that nic salts have a lower pH and can be added in greater quantity without creating a harsh product. They are created by adding benzoic acid to freebase nicotine. This nicotine can be TFN, synthetic, or tobacco derived.

Uses and Applications for Tobacco Free Nicotine

Before it became more widely used in vape juice, synthetic nicotine was primarily used  for nicotine replacement therapy. First appearing as the Patch, there are now a wide range of lozenges, gums, and sprays available. As outlined in the NEJM study cited above, vaping was shown to be more effective than all these methods.

Outside of other traditional methods, vaping and the less than effective nicotine cessation tools promoted by the US pharmaceutical industry, points to nicotine as a potential treatment for autoimmune neurodegenerative diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis.

Researchers established nicotine’s neuroprotection effect, meaning that the alkaloid can help prevent the death of neural cells and facilitate neuron cell regeneration. Synthetic nicotine and tobacco-based nicotine are ideal for research studies and clinical trials to generate robust treatment for the above neurodegenerative illnesses.

Final Thoughts

A lot of ground has been covered here. The upshot is that synthetic nicotine is molecularly identical to tobacco-derived nicotine. The manufacturing process does result in an imbalance of R and S-Isomers not found in nature. This issue is resolved before it synthetic nicotine or TFN ever appear in your vape juice.

Synthetic nicotine is not a tobacco product. It is nearly odorless and imparts less flavor into a given vape juice. This makes it ideal for adult vapers who are looking for optimal flavor clarity.

The materials used to make synthetic nicotine are proprietary, but it is an above-board industry. The laboratories involved in its manufacture are known, reputable and go to great steps to main their supply chain and the purity of the product.

It would be a net gain if the vaping industry could move away from Big Tobacco sourced nicotine, even though synthetic nicotine is a slightly more expensive product. The good news is that Next Gen Lab’s TFN nicotine has dropped the cost to the point where it is now a very viable alternative.

Unfortunately, the rabid anti-vaping lobby and their bottomless check book has targeted synthetic nicotine products. Litigation is probably in the pipeline, as they continue to attack the flavors that adult vapes prefer and funnel former traditional users back onto combustible tobacco products.

We are fast approaching a situation where the only vaping products left on the market will be manufactured by Big Tobacco and their allies. Another term for this is regulatory capture. 

Regulatory capture is not unheard of. It describes a form of corruption where the regulatory agency created to act in the public interest instead advances the commercial interests of the largest stakeholders who dominate the industry.

If you have ever wondered by the waves of regulations like the PACT ACT, flavor bans and PMTAs disproportionately impact the independent vaping industry, while the company considered by most to be responsible for the teen vaping epidemic is prominently displayed at your local gas station, consider this possibility for moment.

Ask yourself why forcing vapers to obtain their electronic nicotine delivery systems (ENDS) at brick-and-mortar stores, whose shelf space dominated is dominated by Big Tobacco made vapes and traditional nicotine ingestion products, was considered a step in the right direction by the federal government.

Synthetic nicotine is their next target.