Synthetic Nicotine: All You Need to Know
The Optics of Traditional Nicotine ingestion and Nicotine
In a September 2018 press release, then FDA commissioner Scott Gottlieb discussed the relationship between nicotine and combustible tobacco.
“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.”
Completely decoupling tobacco and nicotine is not possible. Especially since traditional nicotine ingestion and Legacy Nicotine Companies are viewed as an enemy to public health. Nicotine is part and parcel of the tobacco experience and is extremely addictive. If you do not vape or smoke already, we do not need or want your business.
The only potential rival for the dubious title as Public Health Enemy Number One, the alcoholic beverage industry, is largely shielded from criticism due to the failure of Prohibition a century ago and the fact that the wealthiest Americans continue to imbibe at a higher rate than any other group. This overlooks the CDC report that found 5,000 minors die annually from alcohol and the 130,000 who are admitted to the emergency room.
It has proven to be easy to take away vapes from the marginalized, even at the cost of funneling them back onto combustible tobacco products. Denying access to craft beers and wines enjoyed by the most powerful Americans is a whole different story.
Vaping in the Headlines
Vaping has been lumped in with traditional nicotine ingestion both in the national conversation and in terms of federal, state, and local regulations. A third of high school seniors smoked between 1980 and 2005, and it is no surprise that combustible tobacco products dominate the discussion of nicotine. With the nicotine used in e-liquids derived from the tobacco plant, perhaps it was impossible to expect a country like the US with its juxtaposition of puritanical traditions and progressive nanny state impulses to treat vaping and traditional nicotine ingestion as separate issues.
In the United States, vaping is treated as more than just an electronic nicotine delivery system (ENDs). It has been the target of unjustified bad press. Many of the attacks on vaping headlines have not stood up to scrutiny, but the retraction is never as big as the headline.
A study linking vaping and heart attacks was fully retracted and debunked. The USA Today describes how the scandal plagued researcher responsible for this debunked science, Stanton Glantz, attributed heart attacks that occurred years before the subject had ever vaped to e-cigs. Suffice it to say, the breathless articles and large font headlines that greeted this fundamentally flawed study were nowhere to be found when the results of the study crumbled.
The research of Glantz is largely funded by the Orwellian-named Truth Initiative and Bloomberg’s anti-vaping dollars. It proved very convenient for his sponsors that the huge errors in structure and execution all skewed the results in a way that benefitted his benefactors and hurt the image of vaping. Amazing how it never breaks the other way.
There was also the mysterious lung ailment in the fall of 2019. Blamed on “e-cigs” in the media, vitamin E acetate and THC carts were determined to be responsible. Leafly and assorted states, including some of the least nicotine vape friendly ones in the country such as New York and Utah, figured this out by Labor Day.
Michigan was slow to warn their citizens that nicotine vapes were cleared and THC carts were the issue. This had the advantage of not putting Governor Whitmer’s cannabis industry backers in a bad light. The disadvantage is that adults using THC carts were not warned about the potential peril.
The CDC finally conceded that the issue was THC carts and presented their findings on the Friday before Christmas. The CDC did not find vitamin E acetate in a single sample of commercially available nicotine e-liquid. Adding vitamin E or oils into the VG/PG formula used in nicotine e-liquids simply serves no purpose.
Then there are the flavor bans. Research shows most adult vapers prefer sweet (characterizing in FDA parlance) flavors. Moreover, the top selling product with minors was never an elaborate dessert vape, candy or Reagan-era breakfast cereal inspired e-liquid. A basic mint salt nic found in a prefilled pod and sold in brick and mortar stores dominated the underage market until it was pulled from store shelves.
Vaping versus Nicotine Replacement Therapy
Combustible tobacco products, dip tobacco and vapes are three common methods of ingesting nicotine. In the US, the only recommended method of titrating yourself off nicotine and ending these risky behaviors is nicotine replacement therapy (NRT).
It makes sense on paper. Researchers have established that nicotine in its pure alkaloid form is non-carcinogenic. NRT, usually gums, lozenges and patches containing synthetic nicotine, have been around for decades.
It was only at the start of the second decade of this century that the vaporization of nicotine via e-cigarettes became commonplace. Vaping emerged as an alternative to combustible tobacco products. Traditional nicotine ingestion rates have subsequently declined. And in the United States we are expressly forbidden from drawing any conclusions on this front.
This is not the case everywhere. A study published in the New England Journal of Medicine study found that vaping was twice as effective as nicotine replacement therapy for traditional nicotine ingestion cessation. Critics attempted to move the goal post and pointed out that vapers continued to vape rather than ceasing that activity in an appropriately timely manner.
UK a Beacon of Hope
It is worth noting that the gold standard of total nicotine abstinence demanded by critics of the NEJM study is not the policy of every government. The UK has taken a humane approach.
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.
Much like in the US, the wealthy in the UK have largely ceased traditional nicotine ingestion and did so two decades ago. Vaping is not on the radar as far as an upper-class vice.
Most smokers are from marginalized and underrepresented groups. It is from these groups that most vapers emerge. In the US, the LGBT community is the census defined group most likely to smoke and vape according to the CDC. With access to similar information and nearly identical trends in usage, the UK’s NHS concluded that covering the expense of vaping will save the country money.
The US took a different approaching, attempting to drive the independent vaping industry into the ground. This approach will leave the field open to Legacy Nicotine Companies and their allies. Vapes will be flavored like tobacco and sold on store shelves next to combustible combustible tobacco products
when this policy is executed to completion.
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 combustible tobacco 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 combustible tobacco products
after confirming that vaping prevents house fires. The UK has outperformed EU countries in traditional nicotine ingestion 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. The odds do not seem good.
Severing the Nicotine and Tobacco Connection
In the US, it has not proven as easy to uncouple nicotine and tobacco leaf products like combustible tobacco products. Yet for the typical adult vaper, the connection between nicotine and tobacco is slowly disintegrating. Studies have shown that not much more than a quarter of vapers engage in “dual use”. This describes an individual who vapes and continues to use combustible tobacco products. This number puts to rest the ridiculous myth that vaping is a gateway to traditional combustible tobacco products. While there are still too many vapers who continue to smoke, the number of individuals who transitioned from only vaping to combustible tobacco products is negligible.
In any event, 3 of 4 vapers no longer purchase actual combustible tobacco products. This does not mean that the tobacco industry does not still profit.
Legacy Nicotine Company Links
The most popular convenience store vapes, MyBlu, Vuse, NJoy and Juul, are all made either by tobacco subsidiaries or in partnership with Legacy Nicotine Companies. This is a great reason to support the independent vaping industry.
Until recently, the only source of nicotine for e-liquids was tobacco-derived nicotine. This made it almost impossible to purchase any vaping product without at least a small percentage of the proceeds making it back into the coffers of the tobacco industry. It was only cents on the dollar but still represented a tangible link between e-liquids and tobacco. But this situation is fast evolving.
Affordable non-tobacco and synthetic nicotine products are beginning to hit the market. Non-tobacco nicotine has a much smaller carbon footprint than tobacco extracted nicotine, is manufactured independently of Legacy Nicotine Companies, and has a more neutral flavor free from flavor impurities.
What is Nicotine?
Nicotine is a naturally occurring substance found in members of the nightshade family. It is present in tomatoes, potatoes, green peppers, cocoa plants, and eggplants. The plant with by far the highest concentration of nicotine is the tobacco plant.
Tobacco has been selectively bred for centuries and is the only nightshade plant with enough nicotine in its leaves for commercial nicotine production. The percentage ranges from 5 to 7 percent.
Nicotine is an alkaloid. An alkaloid is a nitrogenous compound of organic plant origin that interacts physiologically with humans. There is a wide range of alkaloids. Quinine, a treatment for malaria, is an alkaloid. Atropine has a wide array of uses as a medical treatment, ranging from mushroom poisoning to elevating low heart rates, is an alkaloid. Morphine is also an alkaloid.
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.
Guide to Non-Tobacco Nicotine
Now that we have provided the lay of the land, it is time to deep-dive synthetic nicotine, non-tobacco nicotine and Tobacco Free Nicotine. We have divided this section into five parts.
- What is Synthetic Nicotine?
- Who Makes Synthetic Nicotine?
- How is Synthetic Nicotine Made?
- How Much Does Synthetic Nicotine Cost?
- Why Make Synthetic Nicotine?
Whether it a Pall Mall, tobacco leaves or a laboratory, the molecular structure of nicotine is always the same: C10H14N2. No matter the source, nicotine always works on the same biological channels.
Non-tobacco nicotine is a purer product than tobacco-derived nicotine due to the extraction process but is otherwise indistinguishable.
Nicotine is chiral molecule, meaning that it is not superimposable as a mirror image. There are two nicotine isomers. The S-Isomer and R-Isomer have totally different biological effects. The R-isomer is inert and occurs in only small amounts in whole leaf tobacco. S-Isomer is the molecule that impacts the nicotine user.
It is easier and cheaper to manufacturer nicotine that is half R and half S isomer nicotine. But as the R-Isomer is inert, it takes twice the quantity of R and S-Isomer nicotine to match the potency of pure S-Isomer.
Who Makes Synthetic Nicotine?
There are two leading producers of non-tobacco nicotine: Contraf-Nicotex Tobacco (CNT) and Next Generation Labs (NGL). CNT is a German based company that makes pure S-Isomer nicotine and has done so since the 1980s. They are responsible for the nicotine used in research and the synthetic nicotine used in nicotine replacement therapy.
These are not fly by night operators. Both companies have patented processes and carefully guarded secrets. Both using cutting-edge technology. Synthetic nicotine is not being manufactured in trailers in Michigan or the Mojave. These are major industrial players creating high-quality products.
NGL is based in California and announced as far back as 2018 that they would be doubling their yearly production capacity in anticipation of increasing demand. NGL producers two types of non-tobacco nicotine.
- R+S isomer combination Tobacco Free Nicotine
- Pure S-Isomer Synthetic Nicotine
NGL is the manufacturer of Tobacco Free Nicotine (TFN). This product is currently the dominant non-tobacco nicotine in the vape juice industry.
Heilbronn, Germany based Contraf-Nicotex-Tobacco or CNT has been manufacturing synthetic nicotine since 1982. Their product is high-end and originally intended for research, and medical purposes. It eventually found its way into nicotine replacement therapies. The price point has dropped over the decades, but its primary uses remain unchanged.
CNT only manufacturers pure synthetic nicotine that contains no R-Isomer nicotine. They consider R-Isomer byproduct. CNT synthetic nicotine is EU certified for pharmaceutical purposes.
CNT’s Torsten Siemen does not think much of R-Isomer nicotine or any non-tobacco nicotine the contains a combination of S- and R-Isomers.
As discussed in a feature in Tobacco Asia, “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.”
“Currently, CNT has a vast production capacity of over 500 metric tons of tobacco-derived nicotine per year, but since synthetic nicotine is made in an industrial setting using various chemical raw materials, there really is no cap as to how much we can potentially produce.”
Cutting the cord with Legacy Nicotine Companies should be a goal of the independent vaping industry and vapers. A move to non-tobacco nicotine would reduce the carbon footprint of e-liquids and help vape juice companies achieve independence from the industrial agriculture machine behind tobacco.
Next Generation Labs
Next Generation Labs and their affordable TFN product currently controls much of the non-tobacco nicotine vape juice market. But what about the presence of R-Isomer nicotine? It is inert and CNT pulled no punches when claiming it was a waste product.
Tobacco Free Nicotine
A July 2021 press release by Next Generation Labs announced the granting of a 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 for the future of S- and R-isomer nicotine formulas.
“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.”
“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.”
If the independent vaping industry moves totally away from tobacco-derived nicotine, the battle between CNT and NGL may shape up as the vape industry’s version of BETA MAX versus VHS.
How is Synthetic Nicotine Made?
Neither CNT or NGL are willing to share their production processes, or the materials they use to manufacture non-tobacco nicotine. Millions have been invested, methods perfected, patents granted, and valuable trade secrets are at stake.
CNT’s process for purification of R-S Isomer synthetic nicotine is available online. Here is a link to their patent.
Synthetic Nicotine Manufacturing
The synthetic nicotine end-product is racemic. Racemic 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 CNT’s patent are the specific raw materials and processes used to create synthetic nicotine in the first place.
Competitive Advantage of Synthetic Nicotine
Not only are the manufacturers unwilling to divulge secrets. Many vape juice and disposable vape makers are not eager to share their source of nicotine. With the more neutral flavor of synthetic and non-tobacco nicotine allowing e-liquid flavors to shine more intensely, this can be viewed as an effort to maintain a competitive advantage.
Here is a statement from Puff Bar: "Our nicotine-based products are crafted from a patented manufacturing process, not from tobacco." The company didn't specify the origins of their non-tobacco nicotine.
The clarity of flavors, often cited as a feature of disposables like the Puff Bar, is proof of concept and non-tobacco nicotine’s potential appeal to adult vapers.
How Much Does Synthetic Nicotine Cost?
Vape juice companies and vapers who want to cut the cord with Legacy Nicotine Companies are surely interested in the comparative cost of tobacco derived and non-tobacco nicotine.
The R&D, logistics, expertise, production cost, and raw materials required to produce Tobacco Free Nicotine are significantly higher than the tobacco extraction process. This is no surprise, as Legacy Nicotine Companies have been churning out liquid tobacco nicotine for decades.
When you compare the costs, one liter of 100mg tobacco-derived nicotine, sufficient for the production of 18,000ml of 6mg vape juice, stands at about $100 (consumer price). For the same amount of e-liquid containing Tobacco Free Nicotine from NGL, the price is around $259.99.
While this difference is significant, the fact that non-tobacco nicotine has cut Legacy Nicotine Companies’s advantage to 2.5 to 1 suggests that with greater scale it could end up being the much cheaper product. It certainly places a smaller strain on the environment and the money spent acquiring non-tobacco nicotine does not go straight into the coffers of Legacy Nicotine Companies.
Why Make Synthetic Nicotine?
Having understood what synthetic nicotine means and the cost involved, let's look at why it is being made in the first place. One advantage is flavor. The neutral flavor of non-tobacco and synthetic nicotine can potentially provide a competitive advantage when compared to tobacco-derived nicotine. A second advantage is that it cuts the vaping industry’s last tie with Legacy Nicotine Companies. The final reason are the endless waves of regulations.
Escalating regulations on the independent vaping industry have proven devastating over the last two years. Restrictions that benefit Legacy Nicotine Companies continue to arrive in the form of the PACT Act, additional vape taxes, PMTAs and other onerous restrictions. That these restrictions seem laser focused on small vape companies has created a scenario that is beginning to mirror regulatory. Regulatory capture is a form of corruption. It occurs when a regulatory agency created to act in the public interest instead advances the interests of the stakeholders they were tasked with regulating.
The vaping industry has naturally responded by shifting away from tobacco products such as tobacco-derived nicotine. Legacy Nicotine Companies clearly have a homefield advantage when tobacco is involved and there is little reason to expect fair treatment.
The Tobacco Control Act states that a tobacco product is "any product made or derived from tobacco and intended for human consumption, including any component, part, or accessory of a tobacco product. Synthetic nicotine is not tobacco-derived and allows small vaping companies to exit a rigged game and hopefully receive fairer treatment in the future.
In other news, traditional nicotine ingestion rates are up for the first time in decades. New restrictions that deny adult vapers their preferred e-liquid flavors and hardware have finally taken hold.