In the past couple of years, “nicotine-like” products have hit the market in the U.S., Europe, Australia and South Korea. They look like nicotine vapes and pouches, with similar flavors and sleek designs. Some provide a nicotine-like buzz. 

But there’s a crucial difference: Outside Europe, these products aren’t subject to government oversight.

Researchers warn that at least one of these products’ nicotine-like chemicals, called nicotine analogs, may be more potent and addictive than nicotine itself — and that these products are sometimes marketed in misleading ways.

What’s in nicotine-like vapes and pouches?

Nicotine analogs are synthetic, chemical compounds that closely resemble nicotine. Some activate the same brain receptors as nicotine, with a similar buzz and addictive properties.

These compounds aren’t new; tobacco companies started researching nicotine analogs in the 1970s in anticipation of future regulations that could reduce how much nicotine would be allowed in their products, according to a study of industry documents. But the companies feared this research would trigger more regulation, so the studies were shelved. 

In 2022, the U.S. Congress acted in response to the proliferation of vapes containing synthetic nicotine. That lab-made compound has the same chemical structure and properties as nicotine extracted from tobacco, so lawmakers authorized the U.S. Food and Drug Administration to regulate products containing synthetic nicotine just as it does those containing naturally occurring nicotine. 

After that, the industry showed renewed interest in nicotine analogs. Products containing these compounds soon appeared on the market.

“These products were intentionally designed to bypass regulation,” said Sven Eric Jordt, a professor of pharmacology and cancer biology at Duke University who has studied nicotine analogs.

Though sales data is limited, research studies say the market for nicotine alternatives is growing. Some companies that produce vapes containing nicotine also produce vapes with nicotine-like ingredients. 

Charlie’s Holdings, a publicly listed company based in the U.S., has shifted its focus to products containing its proprietary nicotine analog as revenue from its nicotine products has dropped, according to its 2024 annual report. In its prior annual report, the company said nicotine alternatives “will give the Company an extraordinary opportunity to capture significant sales and market share in the vapor products marketplace.”

What do we know about the nicotine-like chemicals in these products?

Two nicotine analogs are primarily used in these products. 

6-methyl nicotine is very similar to nicotine; research has shown that it too produces a buzz and is addictive. Popular brands in the U.S., which appears to be the primary market for nicotine alternatives, include Spree Bar, SBX, Outlaw Dip, Happy Hippo and Kumi Six. Trademarked names for 6-methyl nicotine include Metanine, Imotine and NoNic6. 

Nicotinamide, commonly known as niacinamide, is a vitamin used in food supplements and medications to treat vitamin B3 deficiency, skin conditions and other health problems. While also similar to nicotine, studies show nicotinamide doesn’t activate brain receptors like nicotine, so there’s no buzz and it’s not addictive. 

Companies that sell nicotinamide products include Nicotine River, ECBlend and Oasis Vape. Trademarked names for nicotinamide include Nixodine, Nixamide and Nixotine.

The Examination sent requests for comment to Spree Bar and SBX maker Charlie’s Holdings, Kumi Six maker Well Versed, Oasis Vapes, ECBlend, Nicotine River and Happy Hippo. None responded. Outlaw Dip founder Jared Boyce said in an email that the company introduced 6-methyl nicotine products after testing found that it “produced a smoother sensation that many preferred.”

How do these nicotine-like compounds compare to nicotine?

Studies of 6-methyl nicotine’s effects on animals have found that it is several times more potent than regular nicotine. That suggests the same dose of 6-methyl nicotine could be more addictive and more toxic than nicotine, and a consumer would need a lower dose to get the same effect. 

Vapes with 6-methyl nicotine typically list the same dose on the label as those made with nicotine. That said, testing of 17 products from two companies found that most contained lower concentrations of 6-methyl nicotine and nicotinamide than their labels said. 

Nicotinamide doesn’t have the same effect on the brain as nicotine or 6-methyl nicotine.

Are nicotine analogs safe?

There is little safety data on these products, and the risks of inhaling them are unknown, researchers said. 

Although the FDA funds research into nicotine, researchers said it doesn’t fund studies of 6-methyl nicotine.

In animal experiments, 6-methyl nicotine can cause seizures, increased blood pressure and the same neurological and muscular changes seen with nicotine, even at lower dosages, Sairam V. Jabba, a senior research scientist of toxicology and pharmacology at Duke University, told The Examination. 

Irfan Rahman, a professor of environmental pulmonary health and disease at the University of Rochester, analyzed research studies of 6-methyl nicotine and found that it may cause more inflammation in lung capillary cells than nicotine. 6-methyl nicotine can damage those cells, potentially contributing to lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer, he said.

Some companies, such as Happy Hippo, Well Versed (owner of Kumi Six), ECBlend, Charlie’s Holdings and Oasis Vapes, do warn customers that nicotine alternatives could be addictive and carry health risks. 

Because nicotinamide is a vitamin, the benefits and side effects of ingesting it have been well studied. When swallowed, nicotinamide is quite safe at doses under 3 grams per day, said Eun Seong Hwang, a retired professor who researched biology and cancer at the University of Seoul. High dosages may cause insulin resistance, liver damage, kidney disease or nerve damage, according to a study he published in 2020. 

One safety concern has to do with how some nicotine analogs are sold. Some companies sell bulk e-liquids that allow customers or vape manufacturers to create custom blends with different strengths, Jordt said. 

“I'm just concerned that there may be products being made at home or sold by stores that have concentrations that might be really high and toxic,” Jordt told The Examination. 

Meanwhile, there are questions about vape flavorings. Those chemicals, like those used in nicotine vapes, are approved for digestion, not for inhalation. 

“We just don't know what it does when you inhale them for years on a daily basis,” said Hanno Erythropel, a lecturer at the Yale School of the Environment.

Who are these products targeted at?

Though companies say these products should be used only by adults, researchers said their bright, colorful packages appeal to youth. Spree Bar’s packages, for instance, feature an attractive cartoon character for each flavor, each with their own backstory.

Like other types of vapes, those containing nicotine analogs come in flavors such as banana, “blueberry 'n crème,” apple pie and bourbon. “What makes it attractive to the youth is the mango flavor, or whatever other crazy flavors you can buy,” Erythropel said.

While companies’ claims that these products are nicotine-free or tobacco-free are accurate, researchers said that doesn’t mean they are risk-free.

People often buy these products “based on color, flavor and all these kinds of things," Jordt said. "So they may not actually know there is an analog in there. That's the problem." 

What do researchers say about how these products are marketed?

Researchers said there are a couple of ways some companies mislead consumers about how these products affect them: by suggesting that products containing only nicotinamide can provide a buzz like nicotine, and by implying that their products provide a similar effect as nicotine but are less addictive. 

Outlaw Dip says on its website that the 6-methyl nicotine in its pouches “appears to deliver stimulation and satisfaction without gripping your brain as tightly” as nicotine, “making it easier to enjoy casually rather than compulsively.”

The company claims that 6-methyl nicotine gives a “cleaner buzz” that is “smoother and less jittery than nicotine” and “without the sharp crash or cravings.”

These claims are “highly misleading,” with no evidence to support them, Jabba said.

In response to researchers’ statements about the health risks of 6-methyl nicotine, Boyce told The Examination that “we do not make claims about medical outcomes, safety levels, or addiction risk.” 

Some manufacturers market products containing nicotinamide in a way that suggests it has some of the same effects as nicotine, despite no evidence for this claim, researchers said.

Outlaw Dip’s website says that Nixamide, its proprietary form of nicotinamide, has “the same natural effects” as nicotine, including lightheadedness, “‘nicotine buzz,’ elated mood, relaxation, ease of mind, focus, and in some cases spurts of energy.”

Hwang said nicotinamide doesn’t have those effects on the brain. “Nicotinamide is not an alternative to nicotine and does not cause nicotine buzz,” he said.

Researchers are concerned that nicotinamide is being mixed with other analogs to provide a nicotine-like buzz. One study found that six out of eight products listing nicotinamide as an ingredient also contained 6-methyl nicotine, which wasn’t disclosed on the label. 

Researchers told The Examination they suspect some companies use nicotinamide’s designation as a vitamin to appear safe and add 6-methyl nicotine to provide consumers with the buzz they want. 

Jordt said listing only nicotinamide and not 6-methyl nicotine confuses consumers.

What are regulators doing about products containing nicotine analogs? 

In Europe, nicotine analogs in vapes are regulated under the 2014 Tobacco Products Directive. However, the directive does not cover nicotine pouches. An update up for debate this year could change that; in the meantime, it’s up to member states to regulate nicotine analog pouches.

Australia has no regulations on nicotine analogs in particular, but in July 2024, it banned all e-cigarettes and pouches unless they are prescribed by doctors. Even so, one study found that nicotine analogs were for sale in Australia on the black market.

Nicotine analog products are likewise not covered by nicotine regulations in South Korea. 

In the U.S., the FDA told The Examination that nicotine analogs are not “subject to regulation as a tobacco product.” 

On Outlaw Dip’s website, the company celebrates that as a “solid win” that allows it to sell to consumers “without Big Brother stepping in.” Many companies say on their websites that their products are exempt from excise taxes in many states because they aren’t regulated like products with tobacco or nicotine.

Some states are trying to crack down on nicotine alternatives. In January, California imposed new restrictions on flavored products containing “nicotinic alkaloids and nicotine analogs.” 

Jordt said that’s the simplest fix, but he doesn’t think it addresses the potential danger of 6-methyl nicotine because it’s more powerful and there’s not enough data about its long-term risks.