Download Is Nicotine a Gateway to Cocaine Addiction

Is Nicotine a 'Gateway' to Cocaine Addiction
(and Cancer)?
By Maia Szalavitz Friday, November 4, 2011
Some have claimed that tobacco and alcohol are "gateway" drugs that people use before turning to
illicit substances. While causal conclusions are hard to draw, at least one new study in mice shows
that smoking may indeed increase the risk of cocaine addiction by changing gene activity in the
brain. The findings also shed new light on how cigarettes cause cancer and why smoking can harm
developing fetuses.
The study found that when mice received nicotine before and during exposure to cocaine, they were
78% more likely to prefer hanging out in the cage where they got the cocaine, compared with mice
that were not similarly "pretreated" with nicotine. This so-called "place preference" is considered a
reliable measure of how much animals like a drug, and can often predict a substance's level of
addictiveness in humans.
The nicotine-treated mice also showed greater changes in certain brain regions, compared with
animals that received cocaine alone. However, giving the drugs in the reverse order, with cocaine
first, did not increase the animal's addiction to nicotine. Further, stopping nicotine delivery a week
before giving cocaine eliminated the enhanced cocaine-related effects.
The authors also looked at data from a national survey on addictions and found that indeed being a
smoker increased the risk of cocaine addiction. The majority of cocaine users in the group
had smoked cigarettes before they started using cocaine, and started their cocaine use while they
were active smokers.
Researchers have long noted that teens who later become addicted to drugs typically start by
smoking cigarettes and drinking alcohol. But the order of events doesn't necessarily mean that
tobacco or alcohol use leads to other addictions. Rather, it may reflect the fact that these substances
are a lot easier to acquire than illegal drugs. And since most smokers and drinkers do not become
addicted to drugs, the significance of the order in which they are used remains unclear.
"It's hard to know what the most important implication of this study is because it has so many
important implications," says Nora Volkow, director of the National Institute on Drug Abuse, about
the new mouse study appearing in Science Translational Medicine. Volkow wrote an editorial
accompanying its publication.
The study shows at the basic science level that "nicotine has properties that we didn't know about
before," Volkow says, explaining that the drug alters what are known as "epigenetic marks." Unlike
genetic mutations, which change DNA itself, epigenetic changes do not modify genes; instead, they
influence the level of gene activity. In the brain such changes can affect learning and memory.
These epigenetic shifts could help explain why nicotine enhances certain aspects of mental
performance and why it is addictive. Addiction is in many senses a form of learning: essentially,
people who are addicted have learned to like drugs too well, and have difficulty unlearning this
preference. That results in a diminished ability to resist using drugs in contexts that have become
associated with drugs, or when under stress.
Indeed, rehabs have long tolerated cigarette smoking by patients for fear that asking people to make
too many behavioral changes simultaneously would cause them to drop out. "That practice needs to
be questioned," says Volkow, noting that the new research suggests quitting cocaine might be easier
in the absence of nicotine, whether it's delivered through cigarettes or nicotine replacement therapy.
She says other medications should be studied in this setting instead.
Epigenetic changes can also affect a person's risk of cancer. "Nicotine itself is not carcinogenic," says
Volkow, but "nicotine can enhance the carcinogenic effect of other substances so that when
[someone is] exposed to a certain carcinogen [along] with nicotine, it would have a worse effect. This
could be potentially a mechanism by which nicotine could exacerbate the carcinogenicity of other
chemicals."
Could this explain why marijuana smoking isn't associated with the kind of cancer risk that is seen
with tobacco? Volkow thinks the difference probably has more to do with quantity. "I would start
with the dose effect," she says, noting that people smoke a lot more tobacco than marijuana. But she
doesn't rule out the possibility of a qualitative difference. "[There] is definitely a much higher risk of
cancer from smoking cigarettes than marijuana. It's too premature to say that it's just dose; it could
be a difference between the combination of nicotine with other chemicals [in cigarettes] and the
combinations seen in cannabis. We don't know, but someone has to study it."
The epigenetic changes that result from nicotine exposure may also explain why smoking during
pregnancy can be harmful to the fetus. Indeed, research suggests it may be somewhat more harmful
to developing fetuses than smoking crack, contrary to media claims made when that drug first
appeared (though, obviously, taking any recreational drug during pregnancy is not advisable).
The study suggests that it may not be nicotine itself, but the changes in gene activity related to
nicotine, that alters fetal development and causes harm during pregnancy, potentially resulting in
problems like low birth weight and birth defects.
That suggests that nicotine replacement therapy may also be risky in the treatment of pregnant
smokers. "I think that this is a very serious issue that needs to be properly addressed," says Volkow.