Synthetic Nicotine: This Is All You Need to Know

Synthetic Nicotine: This Is All You Need to Know

Nicotine has shared tobacco's bad rap for years, being the primary active ingredient in traditional nicotine delivery sticks. Tobacco has had adverse health effects on smokers' health for years. 

However, synthetic nicotine or tobacco-free nicotine is now available, allowing the compound to step away from tobacco's murky shadow. Given the novelty of artificial nicotine production, consumers have questions, naturally. 

If you wonder what synthetic nicotine is, how it's made, where you can find it, and if it's better than regular nicotine, this post has you covered. Read on to find out! 

What is Synthetic Nicotine?

As the name implies, synthetic nicotine or tobacco free nicotine is artificially made nicotine manufactured in laboratories. Synthetic nicotine companies have designed their product to mimic the effects of that natural plant-based nicotine. However, to fully understand and appreciate synthetic nicotine vape juice, let's begin by understanding the contextual factors that inspired its production.  

Nicotine is one of the phytochemicals that occur naturally in plants. It is a chiral alkaloid found predominantly in plants from the nightshade or Solanaceae family. Over 2500 herbs, vines, and shrubs exist in the Solanaceae family, including dinner table staples like tomatoes, potatoes, eggplants, and bell peppers. However, the nicotine content in most of these plants is nowhere near enough for cost-effective commercial nicotine extraction.  

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 via traditional nicotine delivery systems (e.g. cigarettes) to lung cancer fatalities. The grim discovery led to the rise of government-sponsored campaigns aimed at reducing mortality rates related to traditional nicotine delivery methods. 

Another research study further established that nicotine in its pure alkaloid form is non-carcinogenic. The  study pointed out that other chemical compounds in the tobacco leaf, additives, and the delivery method were the real culprits. According to the study, such secondary compounds and additives, when heated to extreme temperatures during combustion, produce toxic chemicals, including known carcinogenic compounds.  

New technology based companies leveraged these later findings to market alternative nicotine consumption methods and stay relevant after the traditional nicotine delivery systems cessation campaigns. Nicotine vaporization via e-cigarettes and vape devices emerged as a great alternative, utilizing pharmaceutical-grade nicotine extracted from tobacco. 

However, the Food and Drug Authority (FDA) classified tobacco-extracted nicotine as a tobacco product alongside traditional nicotine delivery sticks under the  Center for Tobacco Products (CTP). The CTP regulates tobacco products' production, promotion, and distribution, imposing numerous restrictions on associated parties.  

A case in point is when the  FDA ordered specific e-cigarette manufacturers to recall and discontinue the production of some of their vape juice flavors. The reason behind this drastic action was that the said flavors seemingly attracted the younger side of the Gen Z spectrum. These arguments have been refuted in multiple consumer behavior studies, but the issues relating to flavors remain. Nevertheless, private industry has recognized the need to give adult consumers top-grade quality ingredients in a form that the consumers need. This need led to the production of synthetic nicotine.

Synthetic nicotine vape juice closely mirrors the structure of the tobacco-based nicotine. The primary reason for this similarity is that synthetic nicotine and nicotine derived from tobacco have the same molecular structure; 10 carbon atoms, 14 nitrogen atoms, and two nitrogen atoms (C₁₀H₁₄N₂). So, it attaches to the body's nicotinic receptors similarly to the plant-based nicotine.

Before you hit your search engine to look up synthetic nicotine for sale, check out how it’s made below. 

People in a lab wearing white coats and goggles making synthetic nicotine.

How is Synthetic Nicotine Made? 

Naturally-occurring nicotine sourced from plant sources belongs to the chiral alkaloids group. Chiral alkaloids feature chiral carbon molecules, meaning that although the two carbon molecules look exactly alike, they are opposites like an object and its reflected image.  

The two opposite molecules present in chiral alkaloids make a pair of carbon molecules called enantiomers. Nicotine molecules’ only two enantiomers are S-nicotine and R-nicotine, co-existing in a 1:1 ratio called a racemic mix.  

Although the S-nicotine and R-nicotine in a nicotine racemic mix share most physical and chemical properties, one research  study shows that S-nicotine is the more potent of the two enantiomers. Tobacco-based nicotine has a higher concentration of S-nicotine.

The  patent specification documentation filed for synthetic nicotine manufacturing reveals that its manufacturers rely on racemic mixture resolution to create racemic nicotine. Racemic resolution is the process of using catalysts to separate a racemic mixture into two individual enantiomers, each in its purest form. 

Two processes, chemical synthesis, and crystallography precede the racemic resolution process. Chemical synthesis entails the artificial formation of a mirror image of a single nicotine enantiomer. On the other hand, Crystallography allows the synthesized enantiomer to crystallize in a manner that mimics the rotational direction of the desired enantiomer. In the case of synthetic nicotine, the S-nicotine enantiomer is desirable due to its potency compared to the inactive R-nicotine enantiomer. 

However, note the above information is standard procedure in a branch of chemistry called stereochemistry that focuses on molecular structure and atom arrangement. Fine details like particular chemical reagents used and crystallization methods in the above processes remain a deeply-guarded secret. Most synthetic nicotine brands are currently busy applying for synthetic nicotine production patents and are not keen on divulging their in-house production methods.  

And that concludes our chemistry lesson on how to make synthetic nicotine. However, don’t try the above at home. But the chemistry lesson fails to answer whether synthetic nicotine products like synthetic nicotine vape juice are superior to tobacco-based nicotine products. So next, we explore the similarities and differences between tobacco-based and synthetic nicotine products and determine whether the differences are advantages or disadvantages.  

Vial with a liquid as an example of synthetic nicotine.

Synthetic Nicotine Vs Tobacco-based Nicotine

This content's primary purpose is to empower nicotine consumers and nicotine-curious individuals to make informed purchasing decisions. So, is synthetic nicotine all that, or is it a rip-off? Consider the value proposition below before deciding to buy synthetic nicotine. 

Similarities between Synthetic nicotine (Tobacco free nicotine) And Tobacco-based Nicotine 

Tobacco-free nicotine and tobacco-derived nicotine distillates share more than the word “tobacco hyphenated in their names. Below are their main similarities. 

Effects Tobacco Free Nicotine Has On the Body

Synthetic nicotine vape juice producers formulate it to mimic plant-based nicotine's effects on the body. The synthetic nicotine molecule is only able to do this because it is a replica of plant-based nicotine molecules.  

The synthetic racemic mixture (explained above) used as a template to derive tobacco-free nicotine matches tobacco-based nicotine's naturally-occurring racemic mixture. Using racemic mixture resolution and crystallography selectively to generate more of the S-nicotine enantiomer allows synthetic nicotine to match tobacco-based nicotine's potency.  

Given the two molecules' similarities in molecular structure and potency, they have the same effect on the nicotinic receptors. The nicotinic receptors now usher us into our biology lesson for the day. 

Nicotine receptors are crucial elements in a much larger body system called the  nicotinic cholinergic system. The Nicotinic cholinergic system is an extensive and intricate body system you've never heard of those functions by modulating activity in most parts of the brain. It utilizes neural activation and deactivation to induce various physiological processes. 

Since we cannot exhaust the nicotinic cholinergic system's functions in this post, we will focus on nicotine's interaction with the system. Remember, synthetic nicotine and tobacco-based nicotine molecules attach themselves to the nicotinic system's receptors similarly.  

Nicotinic receptors are present throughout the peripheral nervous system, the central nervous system, the muscles, and the brain. The said receptors function by transmitting signals to the sympathetic system (modulates fight-or-flight responses), and the parasympathetic system induces relaxation and calm, preventing overexertion. 

Nicotine molecules' effect on the nicotinic system receptors explains its contrasting effects. So, the nicotine concentration you purchase is the only factor that impacts the depth or intensity of your nicotine consumption experience. The synthetic or natural nature of the nicotine molecules has nothing to do with it. It feels good to know that you will get the exact stimulant and relaxation effect from a pocket-friendly synthetic vape pen as you would from pricier brands. 

Assembly line of glass bottles with synthetic nicotine inside.

Uses and Applications for Tobacco Free Nicotine 

With all the similarities between synthetic nicotine and tobacco-based nicotine in molecular structure, functionality, and induced effects, the two molecules have similar uses. As seen, nicotine distillate utilization emerged from the need for improved nicotine consumption methods.  

E-cigarette use facilitated the shift from traditional nicotine delivery systems to nicotine consumption, and decades later, vaping took a life of its own, morphing into a cultural phenomenon. The vaping industry utilizes both nicotine molecule types to make nicotine vape products for recreational use. However, synthetic nicotine ejuice and synthetic nicotine salts (called nicotine pouches) are gradually emerging as fan favorites despite their infancy in the vape market.  

Before the advent of vaping, drug dependency treatment centers and individuals utilized products containing nicotine extracts to replace other harmful habits via nicotine replacement therapy. One  research overview shows that NRT has a 50% to 70% success rate in helping individuals trapped in traditional nicotine delivery methods dependency drop the habit.  

NRT products like sprays, chewing gums, sublingual tablets, transdermal (skin) patches, inhalers, and candy-like lozenges relieve nicotine withdrawal symptoms. They help facilitate a seamless transition as the body recalibrates and relearns how to function effectively without nicotine. NRT products’ producers may also use synthetic nicotine in making their products if approved for NRT purposes. 

Unicorn bottle with a drop of synthetic nicotine liquid on the tip.

Differences Between Synthetic Nicotine and Tobacco-based Nicotine 

After establishing the similarities between synthetic nicotine vape juice and tobacco-based nicotine, you probably wonder whether there are distinguishing features of tobacco-free nicotine from tobacco-based nicotine.  

Here are some of the notable differences.  

Production Processes 

We have seen synthetic nicotine production processes using racemic mixture resolution and crystallization to make artificial nicotine molecules. The process exclusively utilizes chemical catalysts and no biological compounds. In contrast, tobacco-based nicotine production utilizes plant matter and organic compounds. Solvent extraction is the most prevalent method used in making tobacco-based nicotine extracts.  

The process entails soaking chopped fresh or cured tobacco leaves in an organic solvent like ethanol, water, or petroleum products like petroleum ether. Such organic extraction solvents soak up the alkaloid molecules from tobacco leaves. The alkaloid extraction duration and the resulting distillate's potency depend on the extraction 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.  

Besides distillation, for alkaloid compounds like nicotine that naturally exist as salts, utilization of an aqueous (water-diluted) mineral acid can replace distillation. The introduction of aqueous mineral acid in the organic solution above causes the alkaloid salt and the acid to form chemical bonds. They create a salt 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.  

Although the production processes for tobacco-free and tobacco-based nicotine are vastly different, one fact cuts across both methods. Do not attempt any of them at home because pure nicotine is highly toxic, and the reagents used in making it are highly corrosive. 

Product Purity 

Did you notice that the word nicotine is missing from the explanation above? Well, there’s a reason for that. While S-nicotine is the dominant alkaloid in tobacco leaves, the plant contains other minor alkaloids including, anabasine, anatabine, and nornicotine. Such alkaloids may bypass the nicotine purification processes highlighted above and make it to the final pharmaceutical-grade nicotine extract. 

The possibility that minor 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. Pristine nicotine quality is a major selling point for synthetic nicotine suppliers selling vape products.  

While the value proposition of exceptional purity is true, synthetic nicotine vape juice and other products are only 1% purer than tobacco-based nicotine vapes. However, that 1% purity level may matter in pharmaceutical applications like neuroprotection research, where precision is crucial. 

Synthetic nicotine vape juice typically features a clear appearance compared to the dark tint in tobacco-based nicotine. Therefore, some synthetic nicotine vape juice sellers may use the clear appearance to position tobacco-free nicotine as a superior form of nicotine. 

Note that the color variations in tobacco-free nicotine and tobacco-based nicotine products are purely cosmetic and have nothing to do with product purity levels. For instance, pharmaceutical nicotine acquired via the alkaloid salt formation process explained above is also clear due to ammonia's bleaching effect. So, when buying tobacco-free vapes and other products, ensure you do not get ripped off with phony value propositions. 

Flavor-carrying Capacity 

Besides alkaloid content purity, another factor that denotes synthetic alkaloids' purity is their characteristic lack of flavor and aroma. Tobacco may not have an elaborate flavor and aroma profile to suit diverse palates, but it has a distinct smell and taste. 

Sadly, (or fortunately for those who like it) the extraction process for tobacco-based nicotine rids it of all impurities except tobacco's characteristic taste and smell. The taste and smell present difficulty when making flavored nicotine vape juices as they come out too strong, resulting in off-flavors in some flavor combinations. Such issues with tobacco-based nicotine's characteristic odors may explain why most nicotine e-cigarettes are either flavorless or menthol flavored. 

In contrast, synthetic nicotine is 100% flavorless and odorless, making it an ideal flavor carrier like diluting juice with pure distilled water. Synthetic nicotine and tobacco-free nicotine's odorless and tasteless characteristic explains the influx of diverse nicotine vape flavors lately. Vape enthusiasts can choose from extensive synthetic nicotine vape juice flavor profiles, including fruity-floral flavors, confectionery flavors, coffee, dessert, and other bespoke flavors. 

The zoomers are especially pleased about this influx of flavors, explaining why synthetic nicotine vaping has high prevalence levels and an ever-growing fan base. Probably, more companies will switch to producing synthetic nicotine vape juice to tap into the vibrant Gen Z vape market soon.  

Does Synthetic Nicotine Impact The Cost of Vape Juice? 

Cost is undoubtedly the most significant difference between synthetic nicotine and naturally-acquired nicotine. The synthetic nicotine production process accounts for the dramatic difference in the cost of production and retail prices between tobacco-based and synthetic nicotine vape juice and other products. 

While synthetic nicotine production seems pretty straightforward, making a complex, naturally-occurring molecule from scratch is no small feat. One of the most notable challenges of artificial nicotine production is getting the final product to have a similar concentration to natural nicotine extracts. The challenge arises because, unlike tobacco leaves' 93% S-nicotine concentrations, the ratio of S-nicotine to R-nicotine synthetic nicotine racemic mixtures is 1:1. 

Moreover, decades of traditional nicotine delivery system production companies investing vast resources in tobacco genetic modification to increase yield means a higher, more potent alkaloid yield from fewer crops. The repetitive procedures and cost of expanding an expensive operation may explain the current cost of synthetic nicotine. Hopefully, future advancements in stereochemistry will lead to the development of significantly more cost-effective production processes. 

Synthetic Nicotine Regulation 

The Food and Drug Authority (FDA) is the regulatory body that oversees the production, marketing, distribution, and sale of tobacco products. And according to the Tobacco Control Act, all tobacco-derived products, including nicotine vapes, fall under the Center for Tobacco Products regulation. One of the rules requires tobacco-based nicotine product manufacturers seeking to launch new products must submit a Pre-market Tobacco Products Application (PMTA) to relevant regulatory authorities. 

However, synthetic nicotine products present a conundrum to the FDA because they technically do not fit into the Center for Tobacco Products' mandate. Moreover, the FDA is hesitant to classify them as drugs under the Center for Drug Evaluation and Research since nicotine is not controlled.  

The regulatory stalemate presents loopholes that synthetic nicotine vape juice companies utilize to launch new products without conforming to PTMA regulations.  

In other developments, the FDA approved the marketing of e-cigarettes and e-cigarette products in an unprecedented move, on 12th October 2021. The regulatory authority cited e-cigarettes' role in facilitating giving up the use of traditional nicotine delivery systems as the primary reason for the move. However, the regulatory authority continues to deny approval applications for flavored e-cigarette products that it deems a threat to public health. 

Flavored synthetic nicotine vape products would fit squarely among e-cigarette products that the FDA deems threatening public safety. The primary reason behind this is that the FDA views the synthetic nicotine vape flavor varieties as targeting a young and vulnerable population.  

Various public interest groups and a section of legislative leaders have echoed the FDA's sentiment about flavored nicotine vapes in general. However, due to the regulatory stalemate over tobacco-free nicotine products, companies making such products can continue to bypass PTMAs. As things stand, the FDA and synthetic nicotine vape companies will be locked in a regulatory tussle for a while. 

Is Synthetic Nicotine and Tobacco Free Nicotine Safe? 

Given the similarity between synthetic nicotine vape juice and nicotine plant extracts in molecular structure and effect on the nicotinic receptors, tobacco-free nicotine is comparatively safe. Generally, nicotine is not the safest compound to consume, and its consumption comes with well-known associated risks. So, the key to staying safe while consuming any nicotine product is moderation. 


Synthetic nicotine and tobacco free nicotine are above-board products, with potential for numerous applications, especially in the vape industry. Many companies are seeing the merits of synthetic nicotine and have switched to using it as the main form of nicotine for their flavored vape juice product lines.


However, the differences between it and tobacco-based nicotine are primarily cosmetic. Regardless, life is too short to spend being thrifty all the time, so splurge in synthetic nicotine and tobacco-free nicotine products once in a while and savor the difference.  



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