Designer Nicotine, The new world of Nicotine Analogues

Introduction

Nicotine analogues are rapidly gaining attention in the vaping world, offering a legal workaround for companies to introduce new products without the same scrutiny from regulatory bodies like the U.S. Food and Drug Administration (FDA). These compounds are similar to nicotine in structure but fall outside the purview of current nicotine-specific regulations, particularly in the U.S. While the European Union (EU) covers these analogues under its broader tobacco laws, the situation in the U.S. is quite different, leaving potential gaps in consumer safety protections.

Nicotine Analogues and Regulatory Loopholes

The FDA's regulations specifically mention freebase nicotine, nicotine salts, and nicotine complexes. However, they do not cover "nicotine analogues"—chemically similar compounds that may behave like nicotine but are not explicitly mentioned in the laws. This regulatory gap has allowed vape manufacturers to market products that contain nicotine analogues without going through the FDA's rigorous premarket approval process.

One example is the compound 6-methyl nicotine, a structural analogue of nicotine. While it shares many of nicotine's biological properties, it is not regulated in the U.S. because it isn’t technically classified as nicotine. As a result, companies can market products with this compound, often labelling them as "nicotine-free" to avoid FDA scrutiny.

For example, a vape product called Spree Bar claims to be nicotine-free but contains 5% of the nicotine analogue 6-methyl-nicotine, which is sold under the tradename Metatine. Despite its chemical difference from nicotine, research has shown that Metatine may be even more potent and potentially more toxic than nicotine, raising concerns about its unregulated use.

The History of Nicotine Analogues

Nicotine analogues are not entirely new. Tobacco companies in the 1970s and 1980s explored these compounds as potential nicotine replacements, anticipating future regulations on nicotine. However, the expected restrictions did not materialize at the time, and research into these analogues faded. With the recent tightening of tobacco regulations, these compounds are making a comeback as manufacturers seek to sidestep the FDA's lengthy and costly approval process.

Uncharted Territory: The Unknown Risks

The biggest concern with nicotine analogues is the lack of research into their effects on human health. Unlike nicotine, which has been extensively studied for decades, very little is known about how these analogues affect the body. Neal Benowitz, a nicotine pharmacology expert, highlights this gap in understanding, pointing out that we lack data on their safety, addiction potential, and long-term health effects.

Preliminary research into 6-methyl nicotine suggests it has a high affinity for nicotinic receptors in the brain, similar to nicotine. However, it has shown to be more potent and toxic in animal studies, raising red flags about its potential dangers to human health. Compounding the issue, manufacturers are not always transparent about the exact concentration of these analogues in their products. For example, tests on Spree Bar found that the actual concentration of 6-methyl nicotine was only 0.6%, significantly less than the 5% listed on the label.

Other Nicotine Analogues on the Market

Another nicotine analogue that has recently emerged in vape products is nicotinamide, a water-soluble form of vitamin B3. While it can be a precursor for nicotine in certain environments, it has no biological activity similar to nicotine. Yet, some manufacturers have marketed vape liquids containing nicotinamide with names like "Nixotine" or "Nic-Safe," suggesting that they target the same receptors as nicotine, despite no scientific basis for these claims.

The real concern arises when these products are mixed with other nicotine analogues like 6-methyl nicotine. In some cases, researchers found that products labelled as containing only nicotinamide had actually been spiked with 6-methyl nicotine, further complicating the safety profile of these products.

The Global Regulatory Landscape

While the U.S. struggles to regulate nicotine analogues effectively, the European Union has broader protections in place. Under the Tobacco Product Directive 2014/40/EU, nicotine analogues have been recommended to fall under the same regulations as nicotine, ensuring they are subject to similar safety standards. This means that products like vitamin vapes, which claim to offer health benefits, would be automatically banned in the EU.

The UK is also moving toward stricter regulations on vape products. The Tobacco and Vapes Bill, introduced in 2024, aims to give UK regulators more power to control the ingredients, packaging, and marketing of vape products, including those containing nicotine analogues. While the incoming government has yet to fully implement these measures, the bill represents a significant step forward in closing loopholes that manufacturers have exploited.

The Future of Nicotine Analogues

As nicotine analogues continue to gain popularity, the debate around their safety and regulation is likely to intensify. The FDA has acknowledged the growing issue but faces challenges in keeping up with the rapid pace of innovation. Meanwhile, researchers like Sairam Jabba are urging regulatory bodies to take a more proactive approach, warning that regulating individual chemicals is a game of "whack-a-mole."

In the absence of clear regulations, consumers must remain cautious about the potential risks posed by nicotine analogues. Until more research is available, these compounds represent an uncertain frontier in the vaping industry, one that could have far-reaching implications for public health.