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Nicotine’s known unknowns: where more research is needed

microscope 300x180The major gaps in scientific knowledge of nicotine are related to delivery methods rather than the substance itself, according to one of the most prominent researchers in the e-cigarette field.

Among the issues that need examining are whether e-cigarettes are as addictive as tobacco cigarettes, and why they seem to deliver less nicotine to users, said Konstantinos Farsalinos of the Onassis Cardiac Surgery Center in Athens.

Noting that it is experienced vapers rather than novices who maximise their uptake of nicotine from e-cigs, Farsalinos said “we need better nicotine delivery if we want the e-cig to succeed as a smoking substitute”, although he acknowledged that that could increase addictiveness.

Possible reasons for the gap in nicotine delivery efficiency include physiological factors such as the ability of e-cig vapour particles to pass deep enough into the body compared with tobacco smoke. Alternatively, the reason could lie with the e-liquid itself, for example if it is degraded through oxidation.

“It is not that we have so many gaps in nicotine research, but in the products that deliver nicotine,” said Farsalinos, speaking at the Global Forum on Nicotine in Warsaw last week.

Knowledge of other products gives little detailed guidance on how e-cigarettes, nicotine and the human body interact, Farsalinos observed.

Snus provides “guidance for nicotine effects, because it’s the only product [other than conventional cigarettes] for which we have long-term studies”, he said, but snus differs importantly from e-cigs in that its use does not involve inhalation.

However, Farsalinos seemed broadly sanguine about the safety of nicotine itself, even pointing out some minor positive health impacts that it may have.

A two-year study of nicotine inhalation in rats had found no ill effects, Farsalinos said, likely referring to the 1996 paper of H.L. Waldum and others.

Sergei Grando’s 2014 study in the journal Nature Reviews Cancer had raised more question marks, but although it incorporated the results of 150 lab studies on nicotine, it didn’t include any clinical studies on humans. “We should be a little concerned [by Grando’s findings], but we have to accept that none of the clinical studies have verified the cell studies,” Farsalinos said.

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    Recent research has raised again the question of whether nicotine may be implicated in the development of some cancers.

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    The need for research goes beyond physical science. At the same conference session, Karl Lund of the Norwegian Institute for Alcohol and Drug Research (SIRUS) said that among the major lacunae in knowledge of snus – the tobacco powder popular in Sweden and Norway, and little-known elsewhere – is an understanding of the sociology and psychology related to the product.

    Among the questions to be answered are the impacts of people using snus at an earlier age than before, the gender characteristics of consumer behaviour, the product’s contribution to personal identity, and its role in achieving personal objectives such as relaxation and weight control.

    Lund also identified a need for knowledge on the implications of dual use of suns with tobacco cigarettes. “Is dual use transient or stable? If it is transient, what is the terminal point?” he asked, pointing out that it could lead to a complete substitution of snus for tobacco, a relapse to smoking, or giving up tobacco altogether.

    Meanwhile, organisers have confirmed that a second nicotine forum will be held next year. Time and place are to be confirmed, but another July date in Warsaw is understood to be likely.

    What This Means: There’s always a temptation for advocates of a position to maintain that the facts are clear, and indeed more than one speaker at the Warsaw conference suggested the positive health impacts of e-cigarettes are so evident that further research can wait. But while waiting for the research certainly shouldn’t bog down innovation, it’s also worth remembering that this is an industry faced by a multitude of Donald Rumsfeld’s “known unknowns” and “unknown unknowns”, some of the known ones significant.

    That applies not just to science, but policy too. Indeed, as a representative of one of the biggest tobacco companies said (rather plaintively): “What is the endgame? What is the acceptability of safe nicotine use in the long term? Is the endgame the end of addiction, end of nicotine use, end of tobacco use? I don’t know.”

    – Barnaby Page ECigIntelligence staff

    Photo: Windy_

    Barnaby Page

    Editorial director
    Before joining ECigIntelligence in early 2014 as one of its first employees, Barnaby had a 30-year career as a reporter and editor for newspapers, magazines and online services, working in Canada, the US and the Middle East as well as his current British location. He has edited publications covering fields including technology and the advertising industry, and was launch editor of the first large daily online news service in the British regional media. Barnaby also writes on classical music and film for a number of publications. Barnaby manages the editorial and reporting teams and works closely with the analyst teams, to ensure that all content meets high standards of quality and relevance. He also writes for the site occasionally, mostly on science-related issues, and is a member of the Association of British Science Writers.

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