|Imaging Study May Help Point Toward More Effective Smoking
Results of a new imaging study, supported in part by the National Institute
on Drug Abuse (NIDA), National Institutes of Health, show that the nicotine received
in just a few puffs of a cigarette can exert a force powerful enough to drive
an individual to continue smoking. Researchers found that the amount of nicotine
contained in just one puff of a cigarette can occupy about 30 percent of the
brain’s most common type of nicotine receptors, while three puffs of a cigarette
can occupy about 70 percent of these receptors. When nearly all of the receptors
are occupied (as a result of smoking at least 2 and one-half cigarettes), the
smoker becomes satiated, or satisfied, for a time. Soon, however, this level
of satiation wears off, driving the smoker to continue smoking throughout the
day to satisfy cigarette cravings.
“Imaging studies such as this can add immensely to our understanding of addiction
and drug abuse," says Elias A. Zerhouni, M.D., Director of the National Institutes
of Health. "These findings suggest that drug therapies or vaccines for smoking
cessation need to be extremely potent to compete with nicotine, which binds so
readily to these receptors.”
The study is published in the August 2006 issue of the Archives of General
“This study illustrates the powerfully addictive impact of even small amounts
of nicotine. Every time a smoker draws a puff from a cigarette, they inhale numerous
toxic chemicals that promote the formation of lung cancer, and contribute in
a significant way to death and disability worldwide,” says NIDA Director Dr.
Nora D. Volkow. “Although many smokers endorse a desire to quit, very few are
able to do so on their own, and fewer than half are able to quit long-term even
with comprehensive treatment. This study helps explain why.”
The scientists, led by Dr. Arthur Brody of the David Geffen School of Medicine
at UCLA, used positron emission tomography (PET) to scan the brains of 11 smokers
and assess nicotine distribution there. During the scanning sessions, the participants
smoked one of five amounts — none, one puff, three puffs, one full cigarette, or
until their craving was satisfied (2 and one-half to three cigarettes). Craving
was measured with the Urge to Smoke scale, which assesses responses to 10 craving-related
questions. The scientists also conducted magnetic resonance imaging (MRI) to
help localize regions on the PET scans.
“We saw on our PET scans that the radiotracer ‘disappeared’ over time as the
nicotine receptors became occupied by nicotine from cigarettes,” says Dr. Brody.
The scientists found that the highest levels of nicotine binding occurred in
the thalamus (a portion of the brain that acts as a conduit for all sensory information
that reaches the brain’s cerebral cortex, and which contains the highest concentration
of these nicotine receptors), the brainstem (which controls various automatic
functions, such as respiration, heart rate, and arousal), and the cerebellum
(the portion of the brain responsible for the coordination of movement and balance).
Results of another recently published NIDA-supported study suggest that a portion
of the cerebellum called the vermis may be a key factor in modulating the brain’s
dopamine and reward systems, and may be more involved in drug abuse and addiction
than previously thought.
“Although craving was only reduced with near total occupancy of these receptors,
there remains the question of whether other, less common types of nicotine receptors
are equally important in tobacco dependence,” says Dr. Brody. “This is an important
area of focus for future research.”
“The central findings of the study suggest that typical daily smokers need to
have these nicotine receptors almost completely saturated throughout the day,
which drives the almost uncontrollable urge to keep smoking,” says Dr. Volkow. “A
more complete understanding of how nicotine affects the brain can help us develop
better therapies for people looking to quit. In addition, since even low levels
of nicotine exposure result in substantial occupancy of these receptors, additional
research needs to address the impact of secondhand, or environmental, tobacco
smoke on nicotine craving.”
The National Institute on Drug Abuse is a component of the National Institutes
of Health, U.S. Department of Health and Human Services. NIDA supports most
of the world’s research on the health aspects of drug abuse and addiction.
The Institute carries out a large variety of programs to ensure the rapid dissemination
of research information and its implementation in policy and practice. Fact
sheets on the health effects of drugs of abuse and information on NIDA research
and other activities can be found on the NIDA home page at http://www.drugabuse.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit www.nih.gov.