One difference between acetylcholine and nicotine is that frequent
exposure to nicotine causes long-term inactivation of the receptors to
which it binds (Fig. 3). In other words, after nicotine binds to and activates receptors, they cannot respond to new nicotine and acetylcholine
signals for a longer period than usual. This is why people who smoke
often find that cigarettes have less and less effect after a while—
causing them to smoke more and more. Because of exposure to nicotine,
their cells’ receptors are not responding to acetylcholine in the way they
used to and need time to return to their normal state.
This also explains why smokers often feel relaxed and even sleepy
after the initial stimulating effect of nicotine disappears. Nicotine is not
readily cleared from the receptors, so the activity of muscles, particularly the heart, slows. This causes blood circulation to slow, and oxygen
is delivered to the body at a lower rate.
Nicotine’s inactivation of these receptors is the biological basis of
nicotine addiction, and it explains why, when people quit smoking or
have too little nicotine in their bodies, they may feel irritable, restless,
hungry, and experience cigarette cravings.
The health effects of nicotine
By essentially hijacking the acetylcholine system, nicotine
can affect brain development. Teens’ brains are still developing—especially the prefrontal cortex, which is the area of the
brain involved in decision-making and planning. The prefrontal cortex does not finish maturing until around age 25.
Researchers have studied what happens to the prefrontal
cortex in adolescent mice and rats exposed to nicotine. By
measuring currents inside their brains, they have found
that nicotine can alter the connections that develop
between neurons. These types of changes can affect
learning and impulse control, which are important for success in school and life.
Nicotine also has effects on other parts
of the body. For example, it constricts blood
vessels by causing cells to release a chemical
called norepinephrine. Norepinephrine helps
keep you alert in difficult or dangerous situations, but too much of it for too long causes
blood pressure to rise, which increases the
risk for heart attack and stroke. More smoking
leads to a higher concentration of nicotine in
the body and more pronounced health effects.
Are e-cigarettes safe?
Whether e-cigarettes should be considered
a healthier alternative to regular cigarettes
is controversial. Research suggests that
e-cigarettes are a better choice than regular
cigarettes for someone who chooses to
smoke, because they allow users to avoid the
toxic slew of chemicals contained in cigarette
smoke. So, e-cigarettes may be an alternative
for people who are already used to smoking.
Findings from one recent study show that
e-cigarettes can help people to quit smok-
ing, presumably by allowing them to gradually decrease their exposure
to nicotine (similar to how nicotine patches work). But this research is
contentious, because other studies have found that e-cigarettes do not
seem to help people who want to quit smoking. In fact, a recent study
funded by the National Institutes of Health found that students who have
used e-cigarettes by the time they start ninth grade are significantly
more likely to start smoking regular cigarettes within the next year than
students who have not tried e-cigarettes.
Many people are concerned that fun flavors, easy accessibility, and
big advertising budgets may lure teens into trying e-cigarettes and
potentially becoming addicted. Evidence from animals, paired with what
we know about the development of the human brain, clearly indicates
that nicotine is addictive, no matter the form in which it is delivered, and
that it has health consequences.
Tavernise, S. E-Cigarettes Top Smoking among Youths, Study Says. The New
York Times, Dec 16, 2014: http://www.nytimes.com/2014/12/17/science/
national-institute-on-drug-abuse-e-cigarette-study.html [accessed Nov
Tavernise, S. Use of E-Cigarettes Rises Sharply among Teenagers, Report Says.
The New York Times, April 16, 2015: http://www.nytimes.com/2015/04/17/
[accessed Nov 2015].
Griffin, R. M. E-Cigarettes 101. Smoking Cessation Health Center, WebMD:
[accessed Nov 2015].
Kristin Harper is a science writer who lives in Seattle, Wash. Her latest
ChemMatters article, “Bacteria Buster! Triclosan Kills Bacteria, but Is It Safe?”
appeared in the December 2015/January 2016 issue.
18 ChemMatters | FEBRUARY/MARCH 2016 www.acs.org/chemmatters
Figure 3. Acetylcholine binds to two types of amino acids, tyrosine (left) and tryptophan (right),
which are on a cellular receptor, through a type of molecular interaction called a cation-π
interaction. These amino acids belong to the protein that makes up the receptor, shown here in a
simplified way as a chain of amino acids. In reality, the chain of amino acids is folded in a complex
HN C CO
Inside the cell Inside the cell
Tryptophan Tyrosine Cation-π interaction
Outside the cell Outside the cell