Category: Uncategorized

  • U.S. Top Doctor: ‘Insufficient Evidence for E-cigarettes’ as a Quitting Aid

    U.S. Top Doctor: ‘Insufficient Evidence for E-cigarettes’ as a Quitting Aid

    There is presently inadequate evidence to conclude that e-cigarettes promote smoking cessation, according to a recent report by the U.S. Surgeon General.

    “E-cigarettes, a continually changing and heterogeneous group of products, are used in a variety of ways,” the report states. “Consequently, it is difficult to make generalizations about efficacy for cessation based on clinical trials involving a particular e-cigarette, and there is presently inadequate evidence to conclude that e-cigarettes, in general, increase smoking cessation.”

    However, during a press conference, Surgeon General Jerome Adams acknowledged anecdotal evidence for the efficacy of e-cigarettes as a quit-smoking aid.

    “I’ve heard powerful accounts from individuals who have used e-cigarettes to quit smoking traditional combustible cigarettes, and there are some studies that are actually reviewed in this report documenting that certain types of e-cigarettes may be associated with quitting in some adult smokers,” he told reporters.

    “But it’s also important that we use the entire body of available science to guide our current recommendations,” said Adams.

    Released on Jan. 23, the new surgeon general report is the first since 1990 to focus solely on quitting smoking, which it says is beneficial at any age.

    Behavioral counseling has been found to increase chances of quitting smoking and seven medications have been approved for helping adults quit smoking: five forms of nicotine replacement therapy and two non-nicotine medications, varenicline and bupropion, according to the surgeon general.

    Remarkably, two-thirds of smokers who try to quit don’t use such approved medications and counseling, while two-fifths are not routinely told by their physicians to stop smoking.

    Cigarette smoking has been on the decline in the United States, reaching an all-time low of 14 percent in 2018.

    According to the report, smoking cessation can be increased by raising the price of cigarettes, adopting comprehensive smoke-free policies, implementing mass media campaigns, requiring pictorial health warnings and maintaining comprehensive statewide tobacco control programs.

    “All of those are proven interventions that save money and save lives,” Adams said.

  • Study: No Link to EVALI Found in Nicotine Products Tested in New York

    Study: No Link to EVALI Found in Nicotine Products Tested in New York

    A new study published on 24 January 2020 in the journal Toxics provides important insight into the recent lung intoxication epidemic referred to as “e-cigarette or vaping product use-associated lung injury” (EVALI).

    The study presents, for the first time, a comprehensive analysis of products used by EVALI patients. Vitamin E acetate was the main finding in cannabinoid liquids. No compound that could be linked to EVALI was found in the two nicotine products tested.

    Researchers from the Wadsworth Center of the New York State Department of Health, the State University of New York at Albany and Albany Medical Center conducted untargeted as well as targeted analyses of 38 liquid samples reportedly used by the first ten cases of EVALI in New York State to identify potential culprits for the serious lung disease epidemic.

    Two of the samples were nicotine-containing liquids, while the rest were illicit cannabinoid liquids. The latter contained relatively low cannabinoid content compared with typical cannabis oil vaporizer liquids, and some had unusual Δ9-/Δ8-tetrahydrocannabinol (THC) ratios. A variety of pesticide residues, such as myclobutanil and bifenthrin, were detected in some samples.

    However, the most striking finding was the identification of vitamin E acetate as a major diluent in 64% of the samples, at levels ranging from 16% to 57% by mass. No unknown compound that could potentially cause EVALI was found in the two nicotine products tested.

    “Our laboratory was the first to identify vitamin E acetate in vaporizer fluids recovered from pulmonary injury patients, which we promptly reported to officials of the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA) and public health officials from numerous states via conference call and via e-mail on August 19, 2019,” said David C. Spink, Ph.D., Chief of the Laboratory of Organic Analytical Chemistry at Wadsworth and corresponding author of the study.

    “Based on our work, the New York State Department of Health issued a press release on September 5, 2019 indicating that vitamin E acetate was a key focus of the Department’s investigation of potential causes of vaping-associated pulmonary illnesses. To investigate potential sources of the vitamin E acetate in the illicit vaporizer fluids, the Department purchased six products marketed as cannabis oil diluents or thickeners via the internet. Three of these were found to be essentially pure vitamin E acetate,” Spink said.

    According to the latest CDC data, there have been 1979 hospitalizations and 57 deaths from EVALI in the US. While the exact cause for the condition is still under investigation, there is a strong association between EVALI and the use of THC-containing vaporizer liquids, and vitamin E acetate has been found in product samples tested by the FDA and state laboratories and in bronchioalveolar lavage fluids recovered from the lungs of patients tested by the CDC.

    While no specific compounds present in nicotine-containing e-cigarette products have been linked to the disease, the contributing cause or causes of illness for individuals reporting use of only nicotine-containing products warrants further study.

  • Charlie’s Chalk Dust to Submit PMTA by May 12 Deadline

    Charlie’s Chalk Dust to Submit PMTA by May 12 Deadline

    Charlie’s Chalk Dust has engaged Blackbriar Regulatory Services (BRS) to assist in the preparation and submission of Premarket Tobacco Product Applications (PMTA) to the Federal Food and Drug Administration (FDA) for some of its e-liquid products.

    Per section 910 of the Federal Food, Drug, and Cosmetic Act (FDCA), all manufacturers of any newly deemed tobacco products, including e-liquid derived from tobacco, must seek authorization approval to sell such products in the United States.

    In July, a U.S. District Court judge issued an order requiring that manufacturers of newly deemed tobacco products submit PMTAs by May 12, 2020. Once submitted, FDA has 180 days to review and respond to timely filed PMTA applications.

    “The PMTA process is challenging and complex,” said Ryan Stump, COO of Charlie’s Holdings. “We are fortunate to have a strong relationship with the leadership team at Blackbriar, a result of prior manufacturing agreements with Avail Vapor, their sister company. We are confident that guidance from BRS will further ensure Charlie’s continued compliance with the regulations put forth by FDA, further supporting Charlie’s leadership in the nicotine e-liquid vape space.”

  • WHO Accused of Blatant Disregard of Truth About Vapor Products

    WHO Accused of Blatant Disregard of Truth About Vapor Products

    The World Health Organization (WHO) is spreading “blatant misinformation” about the potential risks and benefits of e-cigarettes, according to two U.K. researchers.

    In a document released Monday, the WHO expressed reservations about e-cigarettes. E-cigarettes “are harmful to health and are not safe, but it is too early to provide a clear answer on the long-term impact of using them or being exposed to them,” the WHO stated. “There is not enough evidence to support the use of these products for smoking cessation.”

    John Britton, director of the U.K. Centre for Tobacco & Alcohol Studies, countered that e-cigarettes are “clearly less harmful” than combustible cigarettes. “[The] WHO misrepresents the available scientific evidence,” he said.

    “The WHO has a history of anti-vaping activism that is damaging their reputation,” said Peter Hajek, director of the Tobacco Dependence Research Unit at Queen Mary University of London. “This document is particularly malign. There is no evidence that vaping is ‘highly addictive.’”

    Public Health England maintains that vaping is “at least 95 percent less harmful than smoking cigarettes,” but that claim was disputed earlier this month in the American Journal of Public Health.

  • Report: No Support for Youth Vaping Epidemic in New Zealand

    Report: No Support for Youth Vaping Epidemic in New Zealand

    Cigarette use continues to fall among New Zealand teenagers, and vaping is not being taken up by non-smoking youth, reports Scoop, citing new research.

    University of Auckland researchers assessed data from a survey of 27,083 students aged 14 and 15. They found only 0.8 percent were daily vapers who’d never smoked before, with just 3.1 percent of all respondents saying they vaped daily, and 37.3 percent said they’d tried it.

    “Our findings do not support the notion of a so-called vaping epidemic in New Zealand or a large youth population dependent on vaping—a finding consistent with the scarce international evidence,” the researchers said.

    New Zealand government officials have indicated they want to restrict marketing and ban certain flavors.

    “We’re asking the government to closely review the survey’s findings before it starts meddling with adult smokers’ best chance of quitting cigarettes for good,” said Ben Pryor, spokesperson for the Vaping Trade Association of New Zealand (VTANZ).

    “Vaping needs quality manufacturing standards, clear advertising guidelines, and strict R18 enforcement. However, prohibiting flavors won’t make any difference to youth vaping rates. There remains no evidence, here or overseas, that flavors lead to youth vaping and vaping leads to smoking. This latest ASH survey completely reinforces that,” said Pryor.

  • U.S. Presidential Hopeful Bloomberg Plans to Ban All Flavored Vapes

    U.S. Presidential Hopeful Bloomberg Plans to Ban All Flavored Vapes

    Democratic presidential candidate Mike Bloomberg on Tuesday said he would ban the sale of all flavored e-cigarettes and raise taxes on traditional cigarettes if he wins the White House, according to an article posted on thehill.com. 

    Bloomberg, the former mayor of New York City, said he would also push to reduce the amount of nicotine in traditional cigarettes, e-cigarettes and other tobacco products to “nonaddictive levels.”

    Tobacco control has been one of Bloomberg’s top priorities as a philanthropist and as a politician, according to the article. 

    Bloomberg Philanthropies announced in September a $160 million initiative to “end the youth e-cigarette epidemic.” 

    “President Trump has mastered the art of the broken promise — on issues from health care to gun safety — and e-cigarettes have been no exception,” Bloomberg said in a statement. “We need a leader who will stand up to the industry and protect our children’s health.”

    Bloomberg’s plan would also require that health insurance companies cover counseling and smoking cessation medicines for smokers trying to quit without copays or limits on treatment, according to the article. 

    Former Vice President Joe Biden, who is also running for the Democratic nomination, said earlier this month he would halt the sale of vaping products until more research is done.

  • “Vapor is Safer Than Smoking”: WHO Doctor Explains to Committee

    “Vapor is Safer Than Smoking”: WHO Doctor Explains to Committee

    The World Health Organization (WHO) has finally admitted that e-cigarettes are less harmful compared to cigarettes.

    The acknowledgment came from WHO representative Dr. Ranti Fayokun, scientist in the National Capacity-Tobacco Control Prevention of Noncommunicable Diseases during the hearing on vaping regulation conducted by the House of Representatives last month, according to an article on the businessmirror.com.

    Fayokun’s admission was made amid the organization’s cautious stand on e-cigarettes despite the mounting scientific evidence that they are less harmful than traditional cigarettes.

    Public Health England has always maintained that e-cigarettes are 95 percent less harmful than tobacco and has encouraged smokers who can’t quit smoking to switch to the less harmful alternative, according to the article.

    The National Academies of Sciences, Engineering and Medicine in 2018 released a report stating that “completely switching from cigarettes to e-cigarettes will reduce exposure to numerous toxicants and carcinogens found in cigarettes.”

    “They [WHO] are saying if you are a country that cannot produce regulation and cannot enforce regulation, you must ban. That, to me, is a contradiction. A country cannot regulate perfectly, but the last thing it should do is ban because the blackmarket will proliferate. This is an issue that is extremely important to children. If we ban things, if we do not regulate things, we create a blackmarket that does not care about children, that does not care about elderly people, that does not care about us at all,” Dr. Andrew da Roza, an addictions psychotherapist and lawyer said in the congressional hearing, the article states.

    A ban on electronic cigarettes and heat-no-burn tobacco products will only create a black market that will be disastrous to public health, according to international public-health experts who attended a hearing.

    “If you ban them, there will simply be a black market. When the United States banned alcohol in the 1900s, that did not work out,” said da Roza.

    Rep. Weslie Gatchalian, chairman of the House Committee on Trade, said the hearing was called because “the use of ENDS [electronic nicotine delivery system] and heated tobacco products is now a national concern, so much that the President [Duterte] recently issued a directive banning the importation and use of ENDS and HTPs [heated tobacco products] in public spaces.”

    “This committee respects the directive of the President, and sees this as an opportunity for the Philippines to finally regulate this innovative device,” Gatchalian said earlier, according to the article.

    Da Roza, who holds a master’s degree in counseling from Monash University in Australia, said e-cigarettes, HTP products, and other ENDS proved effective in winning smokers away from cigarette smoking which is extremely addictive and powerful.

    “E-cigarettes are twice as effective as NRTs [nicotine replacement therapies],” he said.

    “New technologies give public-health policy a unique opportunity to eliminate cigarettes in a single generation. I truly believe that. We can have a smoke-free world if we use these heat-not-burn products and if we use these e-cigarette products,” said da Roza.

    He said that instead of a ban, the government should support and incentivize safer technologies that will win people away from the scourge of cigarette smoking, according to the article.

    “Any regulation that slows down the developments in science means the people of the Philippines will not benefit from safer products. The government, in my humble opinion, should be investing in research on e-cigarettes and heat-not-burn products,” da Roza said.

  • U.S. FDA Clarifies New Tobacco 21 Rules for Retailers; Rule Effective Immediately

    U.S. FDA Clarifies New Tobacco 21 Rules for Retailers; Rule Effective Immediately

    Since the Federal Food, Drug and Cosmetic Act was amended on Dec. 20, 2019, many U.S. retailers started having issues understanding what the new rules meant.

    In order to help retailers comply, the U.S. Food and Drug Administration (FDA) issued a statement explaining that the new rules make it illegal for a retailer to sell any tobacco product, including all nicotine vapor products, to anyone under 21. The rules are effective immediately.

    The FDA acknowledged that retailers will most likely have to retrain staff and that the agency itself will need to reach out to retailers to assist in re-educating retailers on the changing law.

    While it is expected to take a period of time, the FDA states that it expects retailers to follow the law and do what is necessary to ensure individuals who are purchasing tobacco products are 21 years of age or older. The agency also states that it will continue to only use minors (under the age of 18) for compliance checks.

  • The Gender Gap

    It’s harder for women than men to quit smoking. But a new study found that women are even more likely to experience significant improvements in their vascular health within one month of switching to e-cigarettes.

    No matter who you are, it’s notoriously tough to quit smoking. But it’s even harder if you’re a woman.

    A new study with 200 patients corroborated a plethora of earlier research that concludes it’s harder for women than men to stop smoking. Researchers at the University of Toronto found that women experience more anxiety and depression, which may interfere with their desire and ability to quit smoking.

    But another new study has encouraging news for women who switch to e-cigarettes.

    That research found that smokers—and particularly women—who switched to e-cigarettes enjoyed a significant improvement in their vascular health within one month of switching.

    WHY IT’S HARDER FOR WOMEN TO QUIT

    A 2019 study of more than 200 patients at St. Michael’s Hospital in Toronto supports earlier evidence that gender is the biggest factor in the odds of successfully quitting smoking.

    This study found that women were roughly 50 percent less likely than men to quit smoking. Researchers said the biggest reason was because women are more likely to have mood disorders; 41 percent of women in the study suffered from anxiety or depression compared to only 21 percent of men.

    Beth Abramson, an associate professor of medicine at the University of Toronto and the study’s senior author, said depression and other mood disorders need to be addressed in women who smoke and especially those with a history of heart disease and stroke.

    A propensity toward anxiety and depression is not the only factor making it more difficult for women to quit smoking.

    The female brain also reacts differently to nicotine, according to epidemiological data that shows women’s brains are more sensitive than men’s brains to nicotine’s deleterious effects.

    Although hard-pressed to determine the exact mechanisms underlying women’s greater sensitivity to developing nicotine dependence, researchers from the University of California at Irvine point to “gonadal hormone-mediated sexual differentiation of the brain,” particularly during the perinatal and adolescent periods.

    Exposure to nicotine during these developmental periods can produce long-lasting, sex-dependent changes in neuronal structure and function, they concluded.

    The study, published in 2017 by the National Center for Biotechnology Information, stresses that there are important age and sex differences in nicotine’s effects and opines that preclinical research into tobacco dependence include these factors.

    Other studies conducted at the University of Pittsburgh School of Medicine conclude that women benefit less from nicotine-replacement therapy (NRT) relative to men.

    “Smoking cessation treatment for women must address several other issues that often emerge, and these are most likely to require behavioral counseling tailored to these problems,” said Kenneth A. Perkins, who authored the study.

    “These issues include concern about bodyweight gain, restrictions on medication use in pregnant smokers, variability in mood and withdrawal as a function of menstrual cycle phase, harnessing social support to foster abstinence, and the possibility that smoking-associated environmental cues may be more influential in smoking behavior in women than men,” he said.

    WORRIED ABOUT WEIGHT GAIN

    It’s a well-documented fact that most people, and particularly women, are concerned about gaining weight after they quit smoking. There’s good reason for their concern: Researchers estimate that people gain about 10 pounds on average after they quit smoking.

    No woman is happy gaining weight, even when she knows that quitting smoking is vital for her health in the long run.

    The reason that weight gain is associated with quitting smoking is because nicotine is a stimulant as well as an appetite suppressant.

    That’s one of the key factors behind the growth in e-cigarettes; instead of quitting their daily oral habit or nicotine intake, the former smoker is simply quitting the thousands of chemicals in traditional cigarettes, including over 60 known carcinogens. While nicotine is highly addictive, it is not a carcinogen.

    Multiple studies confirm that even if you gain weight, it’s still much better to quit smoking, as it lowers the risk of cardiovascular disease. Research has found that quitters who gain a few pounds still have about a 50 percent lower risk of heart disease than smokers.

    The same reduction in risk holds true for people with diabetes. That may come as a surprise given that gaining weight can worsen or contribute to an onset of diabetes.

    That’s why researchers and physicians would agree that it’s important to counsel women that some weight gain is to be expected after quitting cigarettes. That is, unless she chooses not to quit cold turkey and switches to e-cigarettes, which makes her less likely to substitute nicotine with food at the times when she used to smoke.

    This type of gender-specific counseling and education could also make a dent in the quit rates for women who smoke.

    THE PROBLEM WITH CHANTIX

    Different women choose many different paths to quitting smoking. One of the more popular methods that’s prescribed by doctors is the drug Chantix, or varenicline.

    However, both men and women run the risk of experiencing this drug’s serious side effects.

    A 2018 study conducted by the Yale Specialized Center of Research found that Chantix was 46 percent more effective in women at the outset. Although after one year, the results were equally effective among women and men. The study’s author hypothesized that sex differences in the brain’s nicotine receptor system may be a key factor why Chantix was at least initially more effective for women.

    However, Chantix has been associated with at least 2,748 adverse events—14.8 percent of all cases—including 293 suicides, 490 attempted suicides and many other cases involving self-injurious behavior or homicidal ideation. The Institute for Safe Medicine Practices, a nonprofit medication watchdog, concluded that Chantix was responsible for more reports of serious drug adverse events than any other drug in the U.S.

    Not surprisingly, these adverse events spurred thousands of lawsuits by families of loved ones who suddenly and inexplicably committed suicide while on Chantix. In March 2013, Pfizer, the drug’s maker, settled 80 percent of these lawsuits out of court for an estimated $273 million.

    Yet the differences between how the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and the media are handling e-cigarettes versus the drug Chantix (varenicline) are dramatic.

    While the FDA drafts increasingly strict enforcement policies for e-cigarettes, it removed the “black box” warning on Chantix that cautioned consumers of the risk of suicide and a host of psychiatric problems, including depression and mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety and panic.

    Regardless of one’s age, it’s becoming easier to buy and take Chantix. In July 2019, Indiana joined 11 other states where anyone can pick up a box of Chantix without a doctor’s prescription.

    A simple search on the CDC website for Chantix and you’ll get only 66 results versus more than 2,200 for e-cigarettes that mention “pulmonary disease,” “lung injury” and “youth tobacco use,” even though e-cigarettes contain no tobacco. Similarly, the FDA website also only lists 78 results in a search for Chantix, and the top result is an update on the September 2016 decision to remove the black box warning.

    “I think Chantix should be recommended by public health officials as a Plan E smoking cessation remedy after cold turkey, e-cigarettes, smokeless tobacco and NRT, since Chantix poses far greater risks than these four other smoking cessation methods combined,” said Bill Godshall, founder and executive director of Smokefree Pennsylvania.

    SMOKE LIKE MEN, DIE LIKE MEN

    For years, it was thought that women were less likely to suffer the same negative consequences as men who smoked. A 2013 study published in The New England Journal of Medicine debunked that notion. After examining data from more than two million women in the U.S., the author, Richard Peto of Oxford University, concluded, “If women smoke like men, they die like men.”

    “There was a big gap in our knowledge,” said Tim McAfee, director of the CDC’s Office on Smoking and Public Health. “This sort of puts the nail in the coffin around the idea that women might somehow be different or that they suffer fewer effects of smoking.”

    Lung cancer is the second most common form of cancer but by far the leading cause of cancer deaths in both men and women. In 2018, over 234,000 new cases of lung cancer—121,680 men and 112,350 women—were diagnosed. More than 154,000 people died of the dreaded disease, including 83,550 men and 70,500 women.

    Lung cancer claims the lives of more women than breast cancer, ovarian cancer and uterine cancer combined. Although lung cancer deaths dropped steadily in men since 1990, these cancers continued to rise in women.

    The fact that women tend to start smoking at a younger age, smoke more cigarettes and continued to smoke in the 1960s and 1970s when men were quitting are the primary reasons behind the dramatic increase in lung cancer deaths among women.

    While advances in treatment and management helped decrease the number of cancer deaths among women, the notable exception is lung cancer. And although it’s more difficult to identify the causal agents of breast cancer, there’s an obvious correlation between smoking and lung cancer.

    Add alcohol into the mix, and women take an even greater risk, according to a European study that followed a group of 380,000 people over age 40 for around 12 years. The mortality rate was anywhere from 1.5 times to 3 times higher for smokers than for people who never smoked.

    And although there were no differences between men and women when only the amount they smoked was taken into account, these risks changed dramatically when alcohol was thrown into the mix. In that case, the mortality rate was 3.88 times higher among women who smoked more than 26 cigarettes and drank more than 30 grams of alcohol a day.

    “Women who consume excessive amounts of alcohol have a significantly higher risk from tobacco use than those who consume little or no alcohol,” the authors concluded.

    But there’s still good news for former smokers. Former smokers who quit before they turn 35 can gain most if not all of that decade back, and even those who wait until middle age to kick the habit can add about five years back to their life expectancies.

    E-CIGARETTES AND WOMEN

    Nicotine exposure during pregnancy is never advised—whether the mother smokes regular cigarettes, e-cigarettes or even uses nicotine patches or gums. Ample research has shown that nicotine use during pregnancy doesn’t just increase morbidity and mortality in the neonatal period, it also increases risk of sudden infant death syndrome and can have lifelong consequences.

    However, research published in November 2019 in The Journal of the American College of Cardiology shows that women who switch to e-cigarettes at other times in their lives can enjoy significant health benefits, including a major improvement in vascular function.

    Smokers, particularly women, demonstrated substantial improvement in their vascular health within one month of switching from traditional cigarettes to e-cigarettes, leading researchers to conclude that switching was an important and significant harm reduction measure.

    Interestingly, the researchers found no difference in vascular effects between those who used e-cigarettes with nicotine and e-cigarettes without nicotine. The authors hypothesized that “early improvement appears to be unrelated to the abstinence from nicotine but rather from other toxic material produced by combustion” in conventional cigarettes.

    In summary, women are at greater risk than men of the deleterious effects of smoking. Yet, quitting is even harder for women for a variety of physiological and psychological reasons.

    But if “first do no harm” is truly the health community’s mantra, then we need to do a better job educating women on the best alternative to quitting tobacco altogether.

    Maria Verven

    The original “Vaping Vamp,” Maria Verven owns Verve Communications, a PR and marketing firm specializing in the vapor industry.

  • Mirror Image

    Even as synthetic nicotine is gaining acceptance among customers, the product remains in a regulatory void.

    Though still a niche compared to tobacco-derived nicotine (TDN), the synthetic nicotine (SN) segment has been growing in the past years. In late August, California-based Next Generation Labs (NGL), a producer of bulk R, R-S and S nontobacco-derived nicotine, announced a doubling of its annual production capacity to meet increasing demand. Orders have been coming from vapor product manufacturers and device cartridge fillers, among other customers, with strong demand in the United States and South Korea.

    Established in 2014, NGL markets its synthetic nicotine under the tobacco-free nicotine (TFN) trademark. Because adult consumers are displaying an increasing preference for nicotine not sourced from tobacco and free of tobacco-derived components, trade customers have been increasing both order sizes and frequency, according to the company. “Our direct clients have reported transitioning from online and vape specialty retail into the convenience segment,” explains Ron Tully, a founding member of NGL.

    Tully is reluctant to share customer or production forecasts, however. “What we can say is that over the past five years, NGL has created this market for nicotine that did not exist prior to our innovation and commercialization of TFN,” he says. “As we have become more established and our TFN nicotine has gained acceptance with manufacturers, the trade and consumers, we have scaled accordingly. The current market demand for synthetic nicotine has increased annually and continues to grow year on year.”

    The substance, initially created in a lab but now manufactured in large-scale production facilities, could play a much greater role in the future, says Torsten Siemann, managing director of Contraf-Nicotex-Tobacco (CNT). “If you think 10 to 15 years ahead and keep in mind the next-generation products market’s development of the past 11 years, tobacco-derived nicotine capacity might reach certain limits at one point,” he says. “Synthetic nicotine can become important in supplying markets such as China, India and Russia where you’ve got many nicotine users who still have to carry out the switch to next-generation products. We see enormous demand there, and the capacity for synthesis of chemicals is unlimited.”

    Since its creation in 1982, the German company has evolved into the world’s leading supplier of tobacco-derived, highly purified nicotine and nicotine derivatives to the pharmaceutical industry. In recent years, CNT has also become a significant provider of pharmaceutical-grade tobacco-derived nicotine to the e-cigarette industry. In 2015, CNT started research on SN. Since 2018, it offers synthetic S nicotine to its customers. The processing takes place at CNT’s exclusive manufacturer, Siegfried, in Switzerland. The companies jointly hold a patent on the manufacturing process of synthetic pharmaceutical-grade S nicotine. The share of SN in CNT’s business accounts for less than 1 percent, according to Siemann. “Presently, synthetic nicotine clearly is a negligible product for us in terms of volume,” he says.

    SAME BUT DIFFERENT

    Whether manufactured naturally or artificially, the nicotine molecule has the same chemical structure, C10H14N2, meaning that it comprises 10 carbon atoms, 14 hydrogen atoms and two nitrogen atoms. What makes it special, independent of its origin, is that it is a “chiral” molecule: It has two stereoisomers that are mirror images of each other.

    The most prevalent form is S nicotine, the physiologically active variant. Its mirror isomer, R nicotine, also occurs in plant-derived nicotine in very small amounts but is basically considered physiologically ineffective. NGL presently focuses on combinations of the R to S isomers for their potential physiological activity. The company has secured a U.S. patent for the use of R-S nicotine in nicotine reduction strategies. But the company also sells full U.S. Pharmecopeia (USP) S nicotine to customers, Tully says.

    The easiest product to create is a combination of S and R nicotine. However, to replicate the natural type, meet the established pharmaceutical monographs and have the same effect, the substance would have to undergo a second process to remove the R isomers. Otherwise, the amount of the combined R-S nicotine would have to be at least doubled.

    Opinions about the use of the R form in synthetic nicotine widely differ. “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,” says Siemann.

    “There is not enough scientific evidence about the effects of the R form, but it is common knowledge in the pharmaceutical industry that enantiomers often exhibit profound differences in pharmacology and toxicology, some of which could be potentially harmful. In the best case, the same quantity of R-S nicotine can be considered to be only 50 percent effective, but we also foresee mislabeling concerns by describing R-S nicotine as equivalent to nicotine USP/EUP. For these reasons, CNT does not sell R-S nicotine.” He adds that his company has tested a number of SN samples, among them products from Chinese and Indian manufacturers, and 100 percent of them were R-S nicotine. “If you look at the European [EUP] and the U.S. Pharmacopeias, the percentage of S isomers in nicotine must be higher than 99 percent,” Siemann explains. “The nicotine used in the pharmaceutical industry needs to have a specific optical rotation that only S nicotine can achieve.”

    NGL markets R, R-S and S nontobacco-derived nicotine. “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,” explains Tully. “Although the uptake pathway for the R isomer is not fully elaborated, there is nothing to indicate that the R isomer is anything other than a positive attribute to the nicotine molecule. 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.”

    BENEFITS

    Synthetic nicotine offers a number of advantages over its natural counterpart. “Manufacturers have access to nicotine in its chiral R and S forms that may offer distinct benefits to consumers in potential takeup pathways for nicotine satiation,” says Tully. In November 2017, the U.S. company reported on research it had carried out on the isomeric character of its SN products. According to a press release, the studies revealed that specific ratios of the R to the S isomers could potentially offer nicotine use at satisfying but nonaddictive or less addictive levels. If proven, the artificially created nicotine might become a useful tool to help producers achieve the U.S. Food and Drug Administration’s (FDA) objective of lowering nicotine content in tobacco products to minimally addictive levels.

    SN can be produced in unlimited amounts independent of nature. In addition, its manufacture doesn’t involve the challenges associated with tobacco cultivation. “Synthetic nicotine requires fewer direct inputs environmentally than tobacco-derived nicotine,” says Tully. “We are not dependent on land availability, soil suitability, fertilizers, herbicides, seeds, labor, firewood, seasonal variations, or any other factor that may impact the finished product as a supply input.”

    Due to its artificial character, synthetic nicotine will also remain untouched by general agricultural challenges, Siemann adds. However, he doesn’t buy the frequently heard argument that synthetic nicotine provides a better taste to e-liquids due to TDN impurities. “This may be true for inferior quality TDN,” says Siemann. “However, CNT’s tobacco-derived nicotine has a purity of more than 99.9 percent, thus ensuring that it is of the highest standard from a sensory perspective.”

    For the time being, SN’s greatest downside is price. Siemann estimates that due to difficulty in purifying the synthetic S nicotine from the R-S form and the comparably small amounts in which SN is currently produced, the artificial variant is about 20 to 30 times more expensive to manufacture than its natural counterpart, a factor that will decrease with growing demand and the upscaling of production.

    Tully notes that the price of SN has come down dramatically over the past five years. “As demand has gone up and production has scaled, pricing has decreased,” he says. “We have moved from pricing from a multiple that was 10 times greater than tobacco nicotine to a most favored nation (MFN) pricing level that is only three to four times the current cost of tobacco-derived nicotine. The suggestion that synthetic nicotine manufacturers are not adjusting pricing to meet market demand is simply not true. Any company that commits to a TFN strategy and works with NGL will receive the benefit of MFN pricing as they scale.”

    REGULATORY VOID

    Despite its growing popularity, SN remains in a regulatory void. Because the product is not derived from tobacco, it does not necessarily fall under the 2009 Family Smoking Prevention and Tobacco Control Act. Neither does SN meet the Federal Food, Drug and Cosmetic Act’s definition of a tobacco product. The FDA has suggested it would evaluate synthetic nicotine products on a case-by-case basis.

    “NGL has made clear to manufacturing customers that TFN is a tobacco-free nicotine designed to offer adult consumers the benefits of a nicotine that is free of all tobacco-derived components and contaminants,” says Tully. “It is an alternative recreational nicotine that aims to allow adult consumers to make a choice to separate their nicotine consumption from all forms of tobacco consumption. That is a laudable aim for all companies in the nicotine business that have the objective of separating nicotine use from tobacco use.”

    Various jurisdictions are trying to regulate TFN in the same way as tobacco nicotine. “We believe treating all nicotine within the same regulatory framework is not in the best interests of adult consumers who are seeking an alternative nontobacco recreational nicotine experience,” says Tully. He argues for science-based regulation of SN.

    Siemann expects regulation of SN in the U.S. as soon as the market has reached a critical size. He is optimistic, though, that the FDA will find a way to regulate synthetic nicotine differently than TDN. “SN could be taxed differently from TDN,” he suggests. “Perhaps it would be an interesting possibility for health authorities to reach public health goals in cooperation.”

    In the EU, SN’s status is similarly unclear. “The revised Tobacco Products Directive, which governs electronic cigarettes in the EU, specifies the use of high purity ingredients,” explains Siemann. “In the case of nicotine, TDN meeting USP/EUP has been adopted as the established norm here. Hence in keeping with this, S form nicotine would be the only equivalent synthetic alternative.”

    FUTURE POTENTIAL

    The future for nicotine from the lab looks bright, according to Siemann and Tully. “There will be markets where products containing tobacco-derived nicotine will not be allowed but where synthetic nicotine will be permitted in consultation with health authorities,” says Siemann. “In the end, we will hopefully see an equivalence between SN and TDN where customers can decide which one to use for their products.”

    “Every market in which tobacco is consumed is a potential market for synthetic nicotine in the future for innovative product entrants for those markets,” says Tully. “Specific short-term opportunities for synthetic nicotine may develop in some markets for regulatory definitional or tax reasons, but those aside, the real opportunity will be in finding a commercialization pathway that marries TFN synthetic nicotine isomers with products that adult consumers are seeking,” he says.

    “The opportunities for TFN nicotine are limited not by the regulatory framework but by the mindset of the tobacco, vape and pharmaceutical [industries] and their willingness to explore the opportunities that the separated and selectively combined R and S isomers of nicotine offer to adult consumers,” says Tully. “A deeper understanding of synthetic nicotine, the uptake pathways of the isomers and the application of this unique product need to be better funded and developed for synthetic nicotine to find its place as the next big leap in adult nicotine consumption.”

    In a world where manufacturers are increasingly promoting products with descriptors such as “natural” and “organic,” it may be difficult to imagine selling a product on its artificial merits. In the case of nicotine, however, “synthetic” may be just the ticket.

    Picture of Stefanie Rossel

    Stefanie Rossel