Mr. Chairman and Members of the Committee, I am pleased to be here with my distinguished
colleagues to discuss current research findings and future research directions on one of the
Nation's deadliest and most costly health problems--use of tobacco products. It is addiction to
nicotine that is at the root of this enormous burden.
Scientific research has determined that nicotine is in fact a highly addictive drug. Nicotine
addiction, like other drug addictions, is characterized by compulsive drug seeking and use, even
in the face of negative health consequences. A testimony to this fact is that most smokers
identify smoking as harmful and nearly 35 million of them attempt to quit each year. Yet only a
very small fraction of them actually succeed.
Emerging basic research is reinforcing what earlier studies have indicated about the highly
addictive nature of nicotine. Let me share with you a sampling of some of our most recent and
interesting research findings.
Recently we have been able to prove what has been only inferred from earlier research, that some
of nicotine's most important effects are exerted through the very same brain circuits as those of
other drugs of abuse. Researchers found nicotine, just like cocaine, heroin and marijuana,
activates dopamine containing neurons in the critical brain pathways that control reward and
pleasure. This finding supports a convergence of data pointing toward at least one major
commonality among all drugs of abuse: they all elevate levels of the neurotransmitter dopamine.
It is this change in dopamine that is believed to be a fundamental root of all addictions.
Another new and exciting finding published just last month, scientists pinpointed a particular
protein, the beta 2 subunit of the nicotinic cholinergic receptor as being essential to the process
of nicotine addiction. Using sophisticated bioengineering tools, these researchers produced a
new strain of knockout mice which lack this important protein. Mice without this receptor would
not self administer nicotine, whereas those who had the receptor readily sought to give
themselves nicotine infusions. This clearly demonstrates that this beta 2 subunit is an important
mediator of nicotine's addictive properties.
Nicotine may not be the only psychoactive ingredient in tobacco, however. Using advanced
neuroimaging (PET) technology we are now actually able to see what tobacco smoking is doing
to the brain of an awake and behaving human being. This poster shows one dramatic effect that
cigarette smoking has on the brain. Here you can see a tremendous decrease in the levels of an
important enzyme known to be responsible for breaking down dopamine, called
monoamine-oxidase- B (MAO-B). The net effect of this reduction in MAO-B is an increase in
levels. Importantly, this particular effect is not caused by nicotine but by some additional,
unknown compound in cigarette smoke. Nicotine itself does not alter MAO-B levels; it affects
dopamine through other mechanisms. Thus there may be multiple routes by which smoking
alters the neurotransmitter dopamine, and, again, this neurochemical is centrally implicated in the
effects of all addictive substances.
Through studies like this we are unraveling the mysteries of not only smoking as an addiction,
but these findings are giving us new information that may be relevant to other addictions as well.
Through NIDA's leadership, the world now has a variety of effective pharmacological and
behavioral treatments to select from to help people conquer their smoking addiction, but we need
more. Addiction researchers have developed a number of new pharmacological weapons to
combat nicotine addiction. For example, several nicotine-replacement therapies, including the
patch and gum are now readily available in local drug stores and supermarkets. In addition our
scientists are working on a number of non-nicotine replacement therapies as well. The
preeminent compound in this line is Buproprion, which you may know as Zyban . Originally
marketed as Welbutrin , an anti-depressant, this compound is showing promising results in
treating nicotine addiction as well.
While we have a number of treatments that have proven to be effective for many people, we still
do not have enough in our clinical toolbox. NIDA will continue to build upon its basic addiction
research portfolio to identify and develop innovative approaches to treat nicotine addiction.
Of course, recognizing that smoking is a complex behavioral as well as a pharmacological
problem, it needs to be approached as such. Thus behavioral interventions play an integral role
in nicotine addiction treatment. To further improve the efficacy of these combined approaches,
we must better understand the antecedents of tobacco use, and learn how to change behavior
patterns. Both research and extensive clinical experiences have taught us that treating the
addiction with just medications is not nearly as effective as when we couple the medication with
a behavioral approach.
We know that more than 90 percent of the people who try to quit smoking, relapse or return to
smoking within one year. The majority of them relapse within a week. There are however, two
and-a-half to five percent, who do in fact succeed on their own. It has been shown that
pharmacological treatments can double the odds of their success. However, a combination of
pharmacological and behavioral treatments can even further improve their odds. For example
when use of the nicotine patch is combined with a behavioral approach, such as group therapy or
social support networks, the efficacy of treatment is enhanced.
Just as with other drugs, ultimately our best treatment is prevention. Twenty years of prevention
research has given us the tools that we need to develop effective programs to prevent people
from beginning to smoke, even young people.
This holds for other drugs of abuse as well. The time of common sense approaches and intuition
in preventing drug use is over. We have a science base for prevention and we need to use it.
Toward this end, NIDA has produced the first ever research-based guide for preventing drug use.
The very same principles espoused in this red book, "Preventing Drug Use Among Children and
Adolescents, " hold for all drugs of abuse, including nicotine. These principles can be applied by
families, schools and communities to ensure the health and well being of future generations.
We are not stopping here however. We are forging ahead to identify risk factors that may make
an individual more vulnerable to addiction. Understanding what makes a person vulnerable, and
how they progress from their first drug exposure to abusing drugs to addiction will enable us to
effectively target our prevention efforts to those who are most at risk. Just as important, however,
is the identification of protective factors, those behaviors, environments, activities, etc. that seem
to enable a person to avoid drug use altogether. Both risk and protective factors may be genetic,
biological, environmental, social or cultural in nature, for nicotine, as well as for all other
It is only through the recognition of tobacco use as an addiction that we will be able to eliminate
many of its detrimental health effects. As with all other disorders, it is research on addiction that
provides hope for even more effective prevention and treatment approaches.
The President stressed that the following five key elements must be at the heart of any national
tobacco legislation: (1) A comprehensive plan to reduce teen smoking, including a combination
of penalties and price increases that raise cigarette prices up to $1.50 per pack over the next 10
years as necessary to meet youth smoking targets; (2) Express reaffirmation that the FDA has full
authority to regulate tobacco products; (3) Changes in the way the tobacco industry does
business; (4) Progress toward other critical public health goals, such as the expansion of smoking
cessation and prevention programs and the reduction of secondhand smoke; and (5) Protection
for tobacco farmers and their communities.
Never before has the momentum for addressing this public health crisis been greater. There are
tremendous scientific opportunities, based on at least two decades of scientific accomplishments.
We must seize the scientific opportunities that now present themselves to ensure that no more
lives are lost to what is ultimately both a preventable and, if not prevented, a treatable disease.
Mr. Chairman, I would be pleased to answer any questions you may have. Thank you.
ALAN I. LESHNER, PH.D.
NATIONAL INSTITUTE ON DRUG ABUSE
U.S. Department of Health and Human Services
COMMITTEE ON LABOR AND HUMAN RESOURCES
FEBRUARY 10, 1998