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On long-term effects: synthetic nicotine itself isnt new chemistry, but its use at scale in consumer products is recent enough that we dont have multi-decade epidemiological data were relying on toxicology and on the fact that nicotine itself, as opposed to combustion products, has a fairly well-understood risk profile

Free nicotine has a greater effect on the sensory nerves in the mouth and throat than protonated nicotine, which contributes to the impact or strength of the cigarette

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Differences by geographical region, however, were complex

38 concluded the following synergistic effects: alcohol and tobacco smoking (OR=4.74