Category: Nicotine

  • The Promise of Synthetic Nicotine

    The Promise of Synthetic Nicotine

    Photo: Oksana Fedorchuk

    As consumer demand for healthier and more environmentally friendly alternatives to combustible cigarettes increases, we should expect greater focus on the benefits of this man-made alternative.

    By Derek Yach

    Tobacco-derived nicotine has been the sole source of nicotine used by pharmaceutical and tobacco companies until recently. The naming of the sector (tobacco sector), the naming of companies (British American Tobacco for example) and the framing of public health policies as tobacco control all show how pervasive and deeply embedded the word tobacco has become despite its scientific name being Nicotiana.

    The dominance of tobacco plants started to wane when pharmaceutical companies developed nicotine-replacement therapies (NRTs) as cessation products. That highlighted the fact that while nicotine is addictive, it is not the source of death and disease caused by the products of combustion. The advent of a wide range of consumer-facing products that also use nicotine (especially e-cigarettes and nicotine pouches) to help smokers switch and/or quit has further increased the focus on nicotine.

    Initially, there was no debate about the source of nicotine since it was assumed to come from the plant. In recent years, several companies have started using patented laboratory processes to develop nicotine from scratch. Many, like Zanoprima, use green chemistry to convert plant-based molecules into synthetic nicotine. Other companies, such as Contraf-Nicotex-Tobacco (CNT), begin with plant-based molecules used in cosmetics and derived from vitamin B.

    Nicotine, like many molecules, exists in two orientations: S-nicotine and R-nicotine; however, nicotine that occurs naturally in the tobacco plant is entirely S-nicotine. Prior to the popularization of synthetic nicotine, this distinction had not been of great practical importance due to its naturally occurring form. Pharmaceutical-grade synthetic nicotine manufacturers such as CNT and Njoy therefore treat R-nicotine as a byproduct of the S-nicotine manufacturing process while Zanoprima’s patented process does not produce R-nicotine at all. Other manufacturers may use methods that may well not meet the high-quality standards of the pharmaceutical industry.

    What Benefits Does It Bring to Consumers and the Environment?

    Consumers increasingly demand information about the supply chain of end products. Leading food companies have led in being transparent about the source of all ingredients in their products with a shift toward those where labor conditions on the farm are known, addition of chemicals are reported, water and greenhouse gas use associated with products are made public and the traceability of food product ingredients is independently audited. Investors are more likely to invest in companies with sound records on these issues.

    So it will be for all future nicotine products.

    For many combustible users, the incentive to switch to a reduced-risk product usually starts with a desire to lower health risks. But for a considerable number, environmental issues are fast becoming reasons to switch, often independent of their health concerns. Again, this has its analogy in the food sector, where companies like Whole Foods have built their main value proposition on an environmental benefit, with health credentials being dubious.

    The tobacco industry emits 84 million metric tons of carbon dioxide (CO2) a year, which is equivalent to 0.2 percent of global CO2 emissions, according to researchers at Imperial College London. Of the total, 20.87 million tons of CO2 come from cultivation, and 44.65 million tons of CO2 come from curing, together amounting to 78 percent of all tobacco industry emissions. Synthetic nicotine has the potential to virtually eliminate these.

    Synthetic nicotine brings tangible benefits to consumers: A better sensorial experience, assurances about the absence of contaminants and a stamp of quality good enough for pharmaceutical companies, to name a few.

    The recent World Health Organization report Tobacco: Poisoning Our Planet paints a vivid picture of the harms of tobacco farming, curing and processing for the environment. More recently, the Foundation for a Smoke-Free World provided a qualitative summary of the potential sources of environmental harm associated with reduced-risk products. Both the WHO and the foundation advocate for the reduction in global tobacco farming, outlining the harms caused by tobacco growth and cultivation on arable land, workers’ rights and malnutrition. It is likely that products created with synthetic nicotine can mitigate many concerns in the product lifecycle. And as companies selling clean nicotine push harder to ensure their products are recyclable and/or reusable, the overall negative environmental footprint will decline further.

    Where Is It Likely to Grow Fastest?

    Today, synthetic nicotine is used in next-generation nicotine products by emerging nicotine pouch companies like NIIN and by mainstream vape companies like Njoy. This trend is set to continue and will gain traction as e-cigarettes and nicotine pouch companies seek medical licensing using synthetic nicotine.

    One example is SMOOD, an up-and-coming next-generation e-cigarette and NRT company based in New York City. SMOOD creates its products as a comprehensive approach to address both health and environmental issues simultaneously. Synthetic nicotine, recyclable hardware and design features to support smokers to quit may well be a signal of what is to come. “We always used nontobacco nicotine due to the absence of minor tobacco alkaloids and metals, both of which are inherent in agricultural production,” says Martin Steinbauer, chief engineer of SMOOD. “Together with repeatable pharmaceutical production processes, nontobacco nicotine improves the toxicological safety of our devices and eliminates carbon emissions, water use and deforestation from tobacco growing. Most importantly, it offers a clean break of nicotine from tobacco finally.”

    Snus and heated-tobacco products are unlikely to shift away from tobacco in the medium term but are lowering the health risks of the tobacco they use through processing changes in the case of snus and by eliminating combustion in the case of heated-tobacco products. For decades to come, tobacco plants will be used in these products as well as in combustibles like cigarettes and cigars where a significant demand from consumers is likely to remain even as overall demand declines.

    Most major tobacco companies already support farmers to diversify. It will be interesting to watch the dynamic within companies with large and growing reduced-risk portfolios who will continue to sell combustibles even as they shift to reduced-risk products to a greater extent in later numbers for several decades. Altria’s purchase of Njoy, Philip Morris International’s acquisition of Swedish Match and BAT’s dominance in the U.S. vape space all signal that these companies will take a twin track approach to nicotine sourcing.

    Who Makes It and How Do They See the Future?

    CNT has stated that synthetic nicotine is currently a niche product with enormous potential. “We see enormous demand there and the capacity for the synthesis of chemical is unlimited.”

    Zanoprima, the only company to use myosmine as the starting material believe that in time synthetic nicotine will become the main source of nicotine in pharmaceutical products as well as in products likely to be sold as both medically approved cessation products, and as recreational products for ex-smokers to use.

    Isn’t It Expensive To Use?

    No—prices have been dropping recently and will continue to do so as demand increases.

    Conclusion

    Health and environmental consumer demand combined with benefits in terms of quality and safety, suggest that synthetic nicotine is set to meet its potential in the coming years.

  • Broughton Adds Extractables and Leachables

    Broughton Adds Extractables and Leachables

    Photo courtesy of Broughton

    Broughton has launched a new extractables and leachables (E&L) testing service for the reduced-risk nicotine industry. The new service will offer tailored E&L studies for products aimed at the premarket tobacco product application (PMTA) and the marketing authorization application (MAA) pathways. 

    According to Broughton, regulatory bodies increasingly focus on the interactions between manufacturing components, nicotine delivery devices and container-closure systems, and the final product formulation. Producers must identify and assess any toxicological risks that could arise via such interactions via E&L studies.

    Aimed at supporting reduced-risk nicotine product categories such as electronic nicotine delivery systems, Modern Oral nicotine pouches and nicotine replacement therapy, the service is available across all stages of the product development lifecycle.

    The new testing service includes study design, extractables studies, extractables toxicology assessments, leachables method development and validation, leachables shelf-life studies and leachable toxicology evaluation.

    “Extractable and leachable studies are essential to the PMTA and MAA regulatory pathways for reduced-risk nicotine products to ensure their safety and demonstrate evidence of mitigating risk. Even in emerging categories, where regulations may not exist, such as nicotine pouches, they should be adopted as a best practice approach to product understanding and stewardship,” said Chris Allen, CEO of Broughton.

    “Our scientific experts and toxicologists have years of combined experience conducting E&L studies across a range of reduced-risk nicotine product and device categories. By offering a one-stop solution for E&L studies, we can ensure a fully integrated approach across study design, extractables study delivery, leachables method development and toxicology assessment with our specialized consultants available to troubleshoot, problem-solve and develop analytical solutions to issues that may arise.”

  • NGOs Challenge Nicotine Delisting

    NGOs Challenge Nicotine Delisting

    Photo: Purilum

    Three groups have sued the government of Malaysia for removing liquid nicotine from the list of controlled substances, reports Bloomberg, citing local media reports.

    Malaysia is preparing legislation that seeks to ban the sale of all tobacco products, including e-cigarettes, to those born after 2007. The NGOs contended that removing nicotine from the list of controlled substances before the tobacco-control rules are in place would allow vape products to be sold openly and legally to anyone, including children.  

    Malaysia’s health ministry removed the restrictions on nicotine liquids and gels on March 31, which allowed the government to tax vape products containing them starting April 1.

    The NGOs argue that the move is unconstitutional, arguing that it went against the recommendation of the Poisons Board.

    The plaintiffs in the suit are the Malaysian Council for Tobacco Control, Malaysian Green Lung Association and Voice of the Children.

  • From Plantations to Nicotine ’Plants’

    From Plantations to Nicotine ’Plants’

    Photo: Taco Tuinstra

    Synthetic nicotine could help promote global food security.

    By Sudhanshu Patwardhan

    The tobacco industry is undergoing rapid transformation. Companies are increasingly offering safer nicotine alternatives to current consumers of risky forms of tobacco. Is it time for them to reassess their supply chains to procure nicotine from nonagricultural sources and in the process free up land for growing crops that can feed the world’s 8 billion people? A study of the economics of tobacco cultivation and nicotine consumption may give us practical answers.

    Millions of hectares of rich, fertile land are used for growing tobacco to meet the nicotine needs of over 1.1 billion tobacco users globally. Except for Swedish-style snus and tobacco used in novel heated-tobacco products, most of the tobacco grown eventually harms public health due to the toxicants arising out of its curing and manufacturing (e.g., tobacco-specific nitrosamines, added chemicals in smokeless tobacco products) and use (e.g., harmful smoke components). On May 31, the World Health Organization marks World No Tobacco Day (WNTD) with an interesting theme: “We need food, not tobacco.”

    Last year, for the first time ever, two U.N. bodies—the WHO and the U.N. Environment Programme)—published a list of the environmental harms from tobacco-related farming, manufacturing, supply chain and consumption. Tobacco-related harms to the environment start from the seed and go well beyond the cigarette and bidi smoke. The WHO notes that globally, an additional 200,000 hectares of land is cleared annually for growing tobacco and curing tobacco leaves that are used in making smoked and smokeless tobacco products. Rich and diverse natural habitats, including pristine rainforests, are being lost to meet the global tobacco demand. It is estimated that 3.7 liters of water are used to make one cigarette. Worldwide, trillions of cigarettes are sold and burned annually. The environmental pollution is not limited to the emitted smoke and the ash but also the cigarette butt litter that refuses to decompose for years. In South Asian countries, spitting smokeless tobacco imposes an additional burden on health and leaves unsightly marks in buildings and roads. Even the pharmaceutical grade nicotine used in medically licensed nicotine-replacement products and e-liquids for vaping products is obtained predominantly from tobacco plants.

    Any slogan that simply calls for more food instead of tobacco oversimplifies the economics of tobacco.

    This year’s WNTD theme intends to put a spotlight on the arable land locked in tobacco plantations that could instead provide food security to the world’s 8 billion people. Indeed, hunger and lack of nutritious food kill millions of people worldwide every year. Feeding the ever-growing world population without denuding forest land remains a big challenge for reasons ranging from environment and climate change to biodiversity. Therefore, in a world with finite arable land, repurposing tobacco farms for growing food are an obvious target for policymakers, environmentalists and economists.

    Sadly, the WNTD theme creates a false dichotomy, unnecessarily pitting tobacco farmers against a hungry world. Alas, one cannot simply switch tobacco farms and farmers to grow alternative food crops with a snap of a finger. Global demand for tobacco continues relatively unabated, thus keeping suppliers invested in a profitable crop. It is also important to remember that tobacco is an unusually hardy plant. Not all food crops can withstand conditions that the tobacco plant can endure. Unlike edible vegetables and fruits, the produce from tobacco plantations is a leaf that is included as a raw material for further processing into a product, thus not subjecting the farmers to the whims and shameful wastage due to strict size and shape requirements of western supermarket buyers. The tobacco leaf markets are utility focused and well supported through longstanding relationships among stakeholders across a sophisticated global supply chain and have lifted millions out of poverty. Any slogan that simply calls for more food instead of tobacco oversimplifies the economics of tobacco.

    The health harms from risky forms of smoked and smokeless tobacco products such as cigarettes, cigars, bidis, hookah, gutkha, khaini, mishri, zarda, etc. are already well known. That knowledge has not made these products or their use obsolete—even today, over a billion people around the world consume these risky products, and more than half of them die prematurely as a result. Nicotine is addictive but is not the cause of tobacco-related cancers, cardiovascular disease and lung disease.

    Many doctors harbor misperceptions about nicotine, wrongly believing that nicotine in the tobacco products causes cancer.

    The invention of nicotine-replacement therapy (NRT) products over three decades ago, in the form of nicotine gums, skin patches, lozenges and mouth sprays, was crucial in realizing nicotine’s role as a medicine in helping quit tobacco and finding these products a place on the WHO’s model essential medicines list. NRT enables smokers and smokeless tobacco users to better manage their cravings and withdrawal symptoms. Still, quitting tobacco and preventing relapse remains a big challenge globally for a variety of interlinked reasons: (i) Pharmaceutical investment and innovation in improved tobacco cessation tools and products has been lacking in recent years, (ii) universal access to affordable and appealing nicotine-replacement products remains poor, and (iii) healthcare professionals around the world are not adequately trained on how to advise their patients to use nicotine-replacement products.

    In fact, many of the doctors themselves harbor misperceptions about nicotine, wrongly believing that nicotine in the tobacco products causes cancer. This limits doctors’ ability to confidently support their patients’ tobacco de-addiction journey using nicotine-replacement principles. The obvious question then is: How do we ensure that current users of tobacco get all the help they can from their healthcare advisers and governments to make quitting tools accessible, affordable, appealing and available? If done at a global level, quitting success will further inspire confidence among consumers, healthcare practitioners and policymakers to accelerate the decline of the demand for tobacco.

    The WHO Framework Convention on Tobacco Control (FCTC) is often elegantly simplified as a treaty for demand reduction, supply reduction and harm reduction strategies. The largest demand arises from the billion-plus cohort of current users of risky tobacco products—and that’s where affordable cessation support and safer nicotine alternatives offer the highest likelihood of practical harm reduction. So, for the agricultural transformation much needed to free up arable land, a global reduction in demand for tobacco will be a key economic driver over time for farmers to actively seek other viable alternatives. It would then be crucial to provide government support and subsidy over a phased reduction in tobacco farming.

    The FCTC dedicates two entire articles in the original treaty text to alternative livelihoods for those in the supply chain and addressing environmental impact—Articles 17 and 18. Particularly in implementing those two articles, little progress has been made in the past 20 years since the treaty came into force. That is because even lesser success has been achieved on a ground-level implementation of the FCTC’s Article 14 that calls for tobacco dependence treatment provision at a national level.

    In recent years, many advances in chemistry and chemical engineering have resulted in new processes and patents issued for synthesizing nicotine from nontobacco raw materials. If the correct isomer of nicotine—the S-isomer—can be manufactured at scale using these processes, that can be revolutionary and indeed game changing. Using such synthetically manufactured nicotine, nicotine-replacement products that are innovative, suitably regulated and where necessary medically licensed can thus be introduced globally for tobacco cessation at low cost and in product formats appealing to current adult smokers and smokeless tobacco users. Agricultural transformation and enhanced food security will naturally follow this purely on economics principles.

  • Bill Threatens Menthol and Nicotine Plans

    Bill Threatens Menthol and Nicotine Plans

    Photo: Rechitan Sorin

    The U.S. House Committee on Appropriations may spoil the Food and Drug Administration’s plans to ban flavored cigars, ban menthol cigarettes and limit nicotine levels in cigarettes, reports Halfwheel.

    On May 17, the committee, which is responsible for allocating funds to various government entities, including the FDA and the Department of Agriculture, unveiled the draft of the Agriculture, Rural Development, Food And Drug Administration, And Related Agencies Bill.

    The proposed language says that FDA cannot use any of the money Congress allocates for it to ban menthol or set nicotine levels, effectively preventing the agency from carrying out the regulations.

    The relevant passages are:

    SEC 768. None of the funds provided by this Act or provided from any accounts in the Treasury of the United States derived by the collection of fees available to the agencies funded by this Act, may be used by the Secretary of Health and Human Services to finalize, issue, implement, administer, or enforce any rule, regulation, or order setting a tobacco product standard that mandates a maximum nicotine level for cigarettes.

    And:

    SEC 769. None of the funds provided by this Act, or provided from any accounts in the Treasury of the United States derived by the collection of fees available to the agencies funded by this Act, may be used by the Secretary of Health and Human Services to finalize, issue, or implement any rule, regulation, notice of proposed rule- making, or order setting any tobacco product standard that would prohibit menthol as a characterizing flavor in cigarettes or prohibit characterizing flavors in all cigars and their components and parts.

    Anti-tobacco activists were aghast. “This bill is a special interest gift to the tobacco industry that would result in more kids addicted to tobacco and more lives lost, especially Black lives,” wrote Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, in a statement. “These shameful provisions give the tobacco industry everything it wants from Congress in exchange for its campaign contributions.”

    The bill is in its early stages and is likely to undergo many modifications.

  • Youth Confused About Nicotine Sources: Study

    Youth Confused About Nicotine Sources: Study

    Photo: kues1

    A study conducted by University of North Carolina researchers and published in Tobacco Control found widespread uncertainty and misperceptions about the sources of nicotine in e-cigarettes among youth.

    “An important contribution from this study is that adolescents don’t understand where nicotine in e-cigarettes comes from,” said first author Sarah Kowitt, assistant professor at UNC Family Medicine and UNC Lineberger Comprehensive Cancer Center, in a statement. “If youth don’t think e-cigarettes are tobacco products like cigarettes, that could increase the appeal of these products. The more youth associate e-cigarettes with cigarettes, the less youth like them.”

    The study also found that while some youth were aware of e-cigarettes that contain synthetic or “tobacco-free” nicotine, most youth were unaware. Most importantly, Kowitt said that the experimental portion of the study revealed that describing synthetic nicotine as “tobacco-free nicotine” increased intentions to purchase e-cigarettes among youth who use e-cigarettes.

    If youth don’t think e-cigarettes are tobacco products like cigarettes, that could increase the appeal of these products.

    “To me, the big takeaway from our study is that the language that is used [to] describe e-cigarettes—on packaging and advertising—shapes adolescent users’ views of the products and their intentions to use them,” said senior author Seth Noar, professor at the UNC Hussman School of Journalism and Media and UNC Lineberger. “The industry has increasingly used the term ‘tobacco-free nicotine’ to describe synthetic nicotine products, and our data strongly suggest that this term may be misleading to youth in ways that increase the appeal of these addictive products.”

    The study is the first to examine how youth understand e-cigarettes with synthetic nicotine. Its goal is to inform efforts by governments and regulatory agencies, including the U.S. Food and Drug Administration,  to more effectively regulate the language used to describe synthetic nicotine products.

  • The Pharmacology of Nicotine

    The Pharmacology of Nicotine

    Photo: Richard Villalon

    The fascinating workings of a widely misunderstood chemical

    By Grant Churchill

    In this article, I will describe the pharmacology of nicotine. I will guide you along nicotine’s journey, starting with how it gets into a person, explain what it does once inside by interacting with specific receptors and finally, how it is inactivated and leaves.

    Due to its chemical properties, nicotine can exist in two forms, depending on acidity, which controls its ability to be absorbed and, in turn, the effectiveness of delivery by different routes of administration. For example, certain forms of smoked tobacco must be inhaled to absorb nicotine, such as cigarettes, whereas others, such as cigar and pipe tobacco, are not inhaled but nicotine is still absorbed.

    It might be useful for the reader to know where I’m coming from in writing this article. I’ve got a professional interest in how drugs work as I do research and teach in this area and find the pharmacology of nicotine fascinating and convey this to medical students. I’ve also got a personal interest as both my parents smoked and died from cancer. So, I wonder if vapes were available 40 years ago, would my parents still be alive? And now, should I be concerned that my adult son is vaping?

    Routes and Rates

    I’ll now describe in more detail how nicotine gets into the body and then the brain. This depends on the fascinating interplay between the route of administration and the chemical formulation, for example, free base or salt of nicotine. Regarding the route of administration, one can have an intuitive and qualitative understanding by considering the number of barriers and distance from the site of application to the brain.

    When inhaled, nicotine has a short journey with few barriers as it is absorbed into the oxygenated arterial blood and goes from the heart to the brain within 10 seconds.

    When swallowed, nicotine has a much longer journey with several barriers as it has to make its way through the stomach on to the small intestine before it can be absorbed into the bloodstream. Then it is in the deoxygenated venous blood that goes to the liver, then through veins to the heart, then through the lungs, where it finally meets the starting point for the inhaled nicotine. Importantly, the liver acts as a paper shredder for drugs and metabolizes them before they are delivered to the rest of the body.

    When applied by a patch, the skin provides an additional barrier before nicotine can enter the bloodstream. Surprisingly, an intravenous injection of nicotine results in a slower route to the brain than inhalation.

    For the intuitive understanding of the routes and rates, one can think about the physiological role of each system. The job of the lungs is to absorb large amounts of oxygen and quickly deliver it to the brain, the importance of which is driven home by considering that consciousness is lost within tens of seconds if inhibited. In contrast, the job of the gastrointestinal tract is to absorb food for energy, which is not needed at the pace of oxygen. Moreover, the job of the liver has evolved to protect us from the remarkably diverse and potentially harmful chemicals we consume in our diets, and in this regard, a drug is just another nonfood or non-nutrient to be inactivated and removed.

    The uptake of nicotine can be more precisely studied quantitatively by monitoring nicotine in the blood and graphing this over time. This reveals an initial increase, a peak and then a tapering off, and numbers can be put to the time and concentration at the peak and the area under the curve. The hit comes from a combination of the speed of the peak and the maximum concentration, and the craving comes from when the concentration falls below a critical activity threshold. The different routes of administration show characteristic concentration over time profiles, with inhaled nicotine showing a fast peak within minutes whereas a patch-delivered nicotine shows a slow increase, taking an hour to peak. This has implications in the user experience and the success of nicotine-replacement therapies for tobacco harm reduction. The rate of decrease in nicotine concentration is similar for all routes of administration due to the same elimination mechanisms: a combination of metabolism by the liver and excretion by the kidney into the urine.

    Crossing Barriers

    The chemical formulation of nicotine as a salt or free base has a major impact on its uptake into the body as only the latter gets in. The chemical basis of this can be understood by considering a vinaigrette, which forms two layers, with the oil floating on a layer of vinegar and table salt (sodium chloride) dissolving only in the vinegar. This demonstrates that molecules can be watery or oily and only mix with their own kind, as summed up by the adage that oil and water don’t mix. Bringing this back to biology, the barriers to uptake of nicotine are cells that form layers like brick walls to separate the contents of our gastrointestinal tract from blood and blood from the organs. The cell’s barrier is its surface membrane called a bilayer, which is an inside out soap bubble with a watery surface and an oily interior forming the barrier. A water-loving nicotine salt cannot cross the oily interior whereas the oily free base of nicotine easily crosses.

    The ability of nicotine free base to easily cross cell membranes is the mechanistic explanation of why nicotine can be absorbed from pipe and cigar smoke held in the mouth whereas cigarette smoke must be inhaled. The processing of the tobacco alters the chemical composition and acidity, resulting in cigarette flue-cured tobacco being acidic with nicotine salt whereas air-cured pipe tobacco is alkaline with nicotine free base. For a fuller explanation, we must again consider how chemistry interacts with biology. Smoke from acidic tobacco (nicotine salt) is less harsh and irritating and can be inhaled deeply into the lungs, where the large surface area (approximately the size of a tennis court) compensates for the inability of the salt to cross membranes.

    Nicotine is always present in both forms, and the acidity controls the relative amounts of salt to free base with only a tenth of a percent in cigarette smoke being the free base compared to 50 percent in pipe smoke.

    The trade-offs between the amount of nicotine that is bioavailable and how deeply it can be inhaled to take advantage of the large surface area of the lungs can also explain the nicotine salt craze in vapes. Nicotine salt formed by adding benzoic acid leads to a “smooth” taste, enabling deep inhalation of higher concentrations of nicotine.

    How it Works Inside

    Now that nicotine is in the body, I’ll describe its effects and how it is active. Nicotine affects cognition, body function and mood. The effects of nicotine on cognition relate to attention and memory and it has been suggested to be a “work” drug as opposed to what most of society would think of as a recreational or “fun” drug. The effects of nicotine on body function mostly relate to heart rate and blood pressure. The effects of nicotine on mood are relaxation and euphoria, arguably two of its major effects as nicotine stimulates a reward pathway in our brains the causes one brain region to stimulate other regions involved in emotion by releasing the neurotransmitter dopamine. Neurotransmitters are chemical messengers that enable communication between the brain cells termed neurons. Very generally, dopamine signals reward or the anticipation of reward—think sex, drugs and rock ’n’ roll, and these days, smartphones—which leads to pleasure and risk of dependence. Nicotine itself acts by mimicking the neurotransmitter acetylcholine, which is involved in learning, memory and attention, which fits with its subjective effects mentioned above.

    Remarkably, all the diverse actions of nicotine arise from it acting on the same pharmacological target: the nicotinic acetylcholine receptor. This receptor spans the surface membrane of a cell and acts as a gated pore that allows ions such as sodium to flow through and trigger a wave of voltage change that sweeps from one end of the cell to the other. The binding of acetylcholine, or nicotine, results in opening and turning on the signal—but with prolonged presence, the gate on the pore jams shut in what is termed “desensitization.”

    So, nicotine has time-dependent effects: Over a period of minutes, the nicotinic acetylcholine receptors open and release dopamine, but after several hours in the presence of nicotine, many of the receptors desensitize, dopamine levels fall, and more nicotine is required to return to the higher level of dopamine. Over a period of weeks, the neuron responds by increasing the number of nicotinic acetylcholine receptors, but most are desensitized, and if nicotine is no longer present, dopamine levels fall, giving rise to physiological withdrawal and addiction. Addiction at the molecular level is related to the structure of the nicotinic acetylcholine receptor, which is made up of five cylindrical subunits arranged side by side in a circle to form the pore. Each subunit is given a Greek letter designation, and in a mouse model, addiction relates to the presence or absence of the beta subunit.

    Chemical Inactivation

    The pharmacological effects of nicotine wear off with time, not from the above desensitization mechanisms but through chemical inactivation and excretion. Nicotine in the blood has a half-life, the time for a given concentration to be reduced by half, of about two hours. Nicotine declines over time through processes common to all drugs in which the underlying principle is to convert a drug from an oily compound to one that is watery. Water is watery due to it being composed of hydrogen and oxygen, therefore introducing oxygen into nicotine makes it watery.

    This chemical transformation occurs in the liver by the enzyme (a molecular machine) cytochrome P450, which forms the major metabolite cotinine. As cotinine has a half-life of about a day, it can be used to examine past nicotine exposure, often by health insurance companies. Cytochrome P450 is a family of enzymes, and different forms are more or less active in converting nicotine to cotinine; the specific form varies between individuals, and certain forms are more frequent in a given ethnic group. For example, a less active form of the enzyme is more prevalent in individuals with Black or Asian heritage. Cotinine or its metabolites are finally removed from the body through the action of the kidneys and excreted into the urine. Again, the effect of acidity on nicotine can be employed by acidifying the urine to increase the fraction of salt, which cannot be reabsorbed back by the body, which thereby increases nicotine excretion.

    Addressing Misunderstandings

    Lastly, there are many controversies surrounding nicotine based on misunderstanding, half-truths and myths. The major health consequences of smoking are due to chemicals other than nicotine produced during combustion of tobacco, so other methods of nicotine delivery provide for tobacco harm reduction. For example, the relative health harms are such that vaping is a method for smoking cessation endorsed by the National Health Service in the U.K. and promoted as such by the government based on the best current scientific evidence.

    Nicotine was used as a pesticide and can be toxic, but as Paracelsus famously stated, the dose makes the poison; any chemical can be toxic, including seemingly innocuous water, or an exceptionally toxic substance such as Botox can be used safely at a lowered concentration. Nicotine may have bona fide therapeutic use beyond smoking cessation in Alzheimer’s disease, Parkinson’s disease, schizophrenia and obesity. Intriguing evidence has been published regarding all these disorders, but the studies were small, leading to equivocal results.

    Larger studies are needed, but the demonization of the tobacco industry for past wrongs is tainting and hampering the ability of scientists and physicians to obtain funding and conduct large, definitive trials. Given that psychedelic drugs, which were made illegal and vilified in the 1960s, are experiencing a renaissance to treat depression and post-traumatic stress disorder, there is hope that nicotine can be separated from smoked tobacco and used or not based on the evidence.

  • Push to Exempt Liquid from Poisons Act

    Push to Exempt Liquid from Poisons Act

    Image: Tobacco Reporter archive

    Malaysian e-cigarette and vapor industry stakeholders have lauded the federal government’s move to exempt nicotine as a controlled substance ahead of new taxation on vape products, reports Malay Mail.

    Excluding liquid nicotine under the Poisons Act will allow the government to introduce proper regulatory frameworks like those in the U.K., New Zealand and Canada, according to the Malaysia Retail Electronic Cigarette Association (MRECA). 

    “Continuing to subject vape products containing nicotine under the Poisons Act does not help as it is not a suitable framework and does not work for the products,” said Datuk Adzwan Ab Manas, MRECA president. “With the exemption, vape liquids containing nicotine can be regulated appropriately, and this is where amendments to existing laws, such as the Control of Tobacco Product Regulations 2004, are required. This is important as it will then see controls in place instead of allowing the products to remain unregulated.”  

    “This is long-awaited news from the entire local vape industry,” said Malaysian Vape Chambers of Commerce Secretary-General Ridhwan Rosli. “The move to exempt liquid nicotine is crucial because now there are rules governing the unregulated industry.”  

    “Vape can be further controlled through existing legislation such as the Control of Tobacco Product Regulations 2004, whose revision would ensure they are not sold to those under the age of 18,” said Malaysian Vape Industry Advocacy president Rizani Zakaria. 

    The Ministry of Health has not consulted industry players since the proposed regulation was announced in the 2023 budget, according to Adzwan and Rizani.

    “We have been in the dark since that announcement with no discussions nor consultation held with the ministry,” said Adzwan. “And the news about the potential exemption on nicotine for vape liquid should be discussed with industry players instead of it being communicated to the health NGOs [nongovernmental organizations]. At the same time, MRECA is of the opinion that the Generational Endgame (GEG) proposal requires further in-depth studies and consultations with all stakeholders, especially the industry players.”

    Healthcare professionals have expressed discontent with the possibility of nicotine being removed from the controlled substances list.

  • MLB Players Switching to Zyn

    MLB Players Switching to Zyn

    Image: aceshot | Adobe Stock

    Major League Baseball (MLB) players are largely switching from smokeless tobacco products to Zyn nicotine pouches, reports Vaping360.

    In 2016, a rule came into effect banning new MLB players from using tobacco products, and many stadiums followed in banning tobacco product use for both viewers and players. Veteran players were allowed to continue using tobacco products, though they had to leave them in the locker room; however, stadiums that banned the products did not offer an exception for players.

    Many players have since switched to the tobacco-free Zyn nicotine pouches. Zyn is manufactured by Swedish Match, which was recently bought by Philip Morris International for $16 billion and holds 64.9 percent of the U.S. nicotine pouch volume as of the second quarter of 2022.

    Zyn and other nicotine pouches do not fall under the tobacco product rules because they contain no tobacco, and there are no rules against MLB athletes using nicotine products.

  • 22nd Boosts Cultivation for New Zealand

    22nd Boosts Cultivation for New Zealand

    Photo: Vasiliy Koval

    22nd Century Group has accelerated a major seed cultivation project for its proprietary reduced nicotine content tobaccos to support local authorities as they work to implement New Zealand’s new reduced nicotine content law starting from this year. The seed will be used to rapidly scale the availability of 22nd Century’s reduced nicotine content tobacco leaf to manufacture cigarettes compliant with New Zealand’s new reduced nicotine content law.

    “New Zealand’s groundbreaking new law will require a sizeable expansion of reduced nicotine content tobacco leaf production to address market needs,” said John Miller, president of tobacco products for 22nd Century Group, in a statement.

    “22nd Century’s ultra-low nicotine content tobaccos are the only commercial scale naturally grown tobacco varieties ready to meet the New Zealand law today. We are moving immediately to ensure sufficient leaf capacity of our reduced nicotine content tobacco to serve the entire New Zealand market as the new law is implemented.”

    22nd Century’s proprietary reduced nicotine content tobacco varieties grow with 95 percent less nicotine than the commercial tobaccos used in making cigarettes for the New Zealand market. Significantly, 22nd Century’s non-GMO tobacco varieties are already compliant with the New Zealand law, which requires all combustible cigarettes to contain less than 0.8 mg of nicotine per gram of tobacco, inclusive of testing variance.

    22nd Century’s expanded growing program, centered in the heart of the U.S. tobacco belt, will produce additional seed sufficient for approximately 2 billion sticks, the entire annual New Zealand cigarette market volume.

    “New Zealand has taken the global lead in tobacco control through its new law, which will reduce the harms of smoking and improve public health and health equity, particularly among minority communities that are disproportionately burdened with the health and economic harms of smoking,” said John D. Pritchard, vice president of regulatory science at 22nd Century.

    “As we increase quantities of our reduced nicotine tobacco seed, 22nd Century is demonstrating conclusively that the tobacco supply chain will pivot quickly to support the ramp up of the national-scale public health program,” Miller added.