describing her first crack cocaine high, Alice said, I
took a hit, like sucked it in really quick and let it make its
way to my brains. It didnt take but a minute. I could
feel my heartbeat getting faster. My eyes and my mouth went
dry. I was sweating all over . . . my muscles were all tight
but it didnt hurt. Its like you get to go to heaven
for a second. No kidding, I thought I was gonna die, but a pleasant
often remember their initial relationship with a drug romantically,
recalling a burst of euphoria, energy, or confidence. If theyre
using with other peoplea group of friends, a relative,
a loverthey recount heightened feelings of camaraderie,
intimacy, and emotional awareness. Some say that, when high,
they had more meaningful conversations, more intense sex, or
a spiritual awakening.
though, the high bottoms out, the glow fades, and the relationship
sours. Even then, addicts cant stop using.
keep on chasing that first high, says Marsha. The
next time doesnt feel as good, and you just chase a feeling.
Chasing makes it so you cant control your habit.
the internal experience of addicts is integral to understanding
addiction itself, says Claire Sterk, an Emory researcher in
the Rollins School of Public Health who quoted Alice and Marsha
in her book Fast Lives: Women Who Use Crack Cocaine.
ask them to describe to me what happens before they take it,
during, and afterthe whole process, says Sterk,
who has studied addicted populations for twenty years. You
cant do that in a lab looking at isolated substances or
through animal studies.
which parts of the brain are affected by drugs like cocaine
and finding ways to block the feelings that lead to cravings
and dependency is at the forefront of current addictions research.
For successful treatments to be devised from this work, however,
findings must be taken out of the lab and applied in the real
where things get complicated, says Sterk, who researches
such topics as multi-generational drug use and mental health,
the increasing popularity of club drugs like ecstacy, and the
relationship between drug use and sexually transmitted diseases.
is one of a number of Emory researchersin fields from
public health to neurologywho are studying the biological
and social roots of substance abuse. From pinpointing the pathways
drugs follow in the brain to determining how cravings arise
by using guided imagery with recovering addicts, these researchers
are looking for clues about effective ways to prevent and treat
of the studies focus on cocaine, an especially addictive stimulant
that seems to create long-term changes in the brain. About one
and a half million Americans are thought to be addicted to cocaine,
according to the National Institute of Drug Abuse, which funds
much of the research being conducted on addiction.
Kuhar, the Charles Howard Candler professor of neuropharmacology
at Yerkes National Primate Research Center, is leading a team
of researchers trying to find cocaine analoguesdrugs
that will dull or eliminate the desire for cocaine, much as
methadone does with heroin.
says Kuhar, is the drive to repeat something in spite
of negative consequences for you personally, your family, or
your community. Much like heart disease, he says, drug
addiction can be examined not only from a medical perspective
but through genetic, environmental, and behavioral lenses. Still,
he believes the answer to why people become addicted to drugs
is writ at the molecular level and remains in large part a mystery.
know drugs bind to certain receptors and cause certain changes.
But we dont know all of the changes and which ones are
critical, he says. We believe it is the accumulation
of these changes that is important in addiction, since the duration
and frequency of drug use is related to the magnitude of dependence.
impact deep, primitive portions of the brain, Kuhar says, which
means their use is not simply under the control of reasonmotivational
desires and urges become dominant.
addictive drugs stimulate the same areas of the brain as food,
water, and sex. Some drugs make you feel good, but thats
not necessarily why people become addicted, Kuhar says.
The whole reason reward and reinforcement pathways exist
in the brain is for survival. Certain drugs turn on
those areas of the brain, and those drugs are the ones that
make you want to take them again and again.
researching the effects of cocaine, Kuhar and his colleagues
discovered the exact mechanism by which the drug disrupts the
brains levels of dopaminea chemical that helps brain
cells communicate and that in larger-than-normal concentrations
can cause feelings of euphoria. Cocaine raises dopamine levels
in the brain by acting almost like a stopper in a drain. With
chronic cocaine use, the dopamine system can become reset,
and can take months or years to return to normal even after
drug use has stopped.
next step is to develop medications that will help cocaine abusers.
Kuhar and collaborators from the Research Triangle Institute
in North Carolina developed a class of drugs called phenyltropanes,
which affect the same brain systems as cocaine and related drugs
but have lower potential for abuse and minimal side effects
in the brain, these cocaine analogues bind to the same dopamine
transporters that cocaine targets but, because they enter the
brain more slowly and are longer-lasting, it is hoped that users
wont get the rush.
selected analogues were tested in rats, Leonard Howell, a behavioral
neuroscientist in psychiatry at Yerkes, tested the drugs in
squirrel monkeys that had been trained to self-administer cocaine.
The animals cocaine use went down. Phenyltropanes, says
Howell, appear to allow a gradual restoration of normal dopamine
function, avoiding the precipitous highs and lows . .
. that send people running back to their habit.
cravings can feel overpowering, says addiction psychiatrist
Karen Drexler, an assistant professor in Emorys School
of Medicine who works at the Atlanta Veterans Affairs Medical
who directs the substance abuse program at the VA, is grateful
for the methadone clinic on the hospitals ground floor,
which opened this summer. Thirty-four recovering heroin addicts
visit the clinic to swallow a daily dose of the drug, which
binds with the brains opiate receptors but is longer-acting
and doesnt provide the same rush. These recovering addicts
can take methadoneeven though it is addictive as wellfor
their whole lives, Drexler explains, just as a diabetic would
is counterintuitive, but its proven to be immensely effective
at reducing crime, and keeping them healthy and out of jail,
she says. They go from being drains on society to productive
members of society.
is no such alternative yet for cocaine addicts in recoverythe
bulk of Drexlers case load.
75 percent of our patients who present for help with their addictions
says their drug of choice is cocaine. The thing thats
really devastating about cocaine is that people are able to
stop taking it fairly easilythey just cant stay
off it, she says. When people are using alcohol
or heroin heavily then stop, they get sick and have withdrawal
that can be life-threatening. With cocaine, that doesnt
happen. People may be tired and depressed, but they arent
terribly sick. They can do just fine until, say, their next
paycheck comes. Then they have a very strong craving that seems
is using positron emission tomography (PET) to determine the
areas of the brain that are most active during these periods
of desire for the drug. She uses personalized scenarios based
on interviews with the addicts that detail the environmental
and internal cuesfeelings, smells, tastes, people, placesassociated
with past drug use. The volunteer is asked to mentally re-enact
the scene as they listen to it on headphones, while a ninety-second
brain scan is conducted to see which neuropathways light up.
is the transcript of a scenario from one of Drexlers clients:
Saturday night and Im ready to do my usual thing. I want
more than anything to feel the rush I used to feel. . . . Im
ready to make the buy. . . . Once I get to his house we chill
for a minute and then Im on my way home. Now, as quick
as I can, I drive home, lock all the doors, turn on the TV and
radio, and take a hot shower. Now Im ready and I can feel
the beads of perspiration all overI am so restless. God,
just thinking about getting high makes my heart beat faster.
I get all my utensils together, get comfortable on the couch
and get ready to take the first, incredible hit. Finally I take
my lighter out of my pocket, put it to the stem and smell the
first burning of the stuff thats going to take me to the
areas of the brain that respond, Drexler found, are the amygdala
(stimulus and reward), the nucleus accumbens (incentive and
motivation), and the anterior cingulate cortex (anticipation.)
These are essential pathways, also activated during activities
like eating and sex. The brain, she says, starts
to think that cocaine is essential to survival.
support groups for recovering addicts at the VA, Drexler often
lectures with a model of the human brain, pointing out the central
areas responsible for cravings. One recent morning, six clients
gathered in a small room on the fifth floor, listening intently.
seems baffling, how a substance can get a hold of and control
your life instead of you controlling the substance, Drexler
said. I want to help in your understanding of addiction
as a brain disease, not just a bad habit or a moral problem.
A lot of times, we struggle with shame. But it truly is a disease,
like diabetes or heart disease.
tells the group about twin studies and the strong hand genetics
seems to play in addictions.
a triplet, says Michael, a calm, soft-spoken man who said
he held a job but used to binge on weekends. My sister
doesnt even drink. But my brother and I were curious about
a talkative mother who has struggled for many years with drugs,
said, As my addiction progressed, and my life became unmanageable,
I would still want more cocaine. After the first hit, I was
on a mission 24/7. I knew the only things that could stop me
were death or the police. I was high-risk to start withit
runs in my family. But I have daughters, and I dont want
my angels to walk the road Ive walked.
a middle-aged man who smiles frequently and calls Drexler doc,
was full of questions about the nature of addiction. Alcohol
triggers everything for me, he said.
not alone in the alcohol-cocaine connection, Drexler answered.
Two things happen when you drink. One is that you prime
the pumpyour brain gets the message that its time
for you to use. And secondly, it decreases your ability to use
your frontal cortex and think logically.
group started talking about the valuable parts of their lives
they had sacrificed to drugs: jobs, family, money, friends.
Right. Drugs have hijacked those pleasure pathways,
payday came, or an event to celebrate, or stress, the solution
was to turn to the drugs. You want what you want when
you want it, said Darren, who said that while he was using
he was on a continuous quest to find new and better highs.
learning is working against you, Drexler replied. But
it can work for you, if you learn to recognize high-risk situations.
other researchers are focusing on areas of the brain that respond
to cocaine and how addicts can resist these intense cravings,
Winship Distinguished Research Professor and Chair of the Department
of Chemistry Jay Justice is trying to determine which strands
of proteins, down to the exact amino acids, are targeted by
like dopamine, norepinephrine, and serotonin are affected by
drugs of abuse as well as by therapeutic drugs such as antidepressants,
says Justice, who teaches the course Chemistry of Drugs
in the Brain.
cocaine is especially insidious. The brain adapts to the
continued presence of the drug, he says. You get
a real problem when you take it away . . . cravings, relapses.
Its not the same brain anymore.
brain itself seems remarkably attuned to these effects, says
Justice. In research conducted by his team, rats that were trained
to press a lever to administer cocaine to themselves would adjust
the amount if researchers doubled or halved the dose. Somehow,
he says, they knew what was going on and regulated the
Justice believes, is a brain state. This is not an existential
problem that exists in the ether, he says. I dont
believe in a brain-mind dualism. Everything has a molecular
walks through his lab, where graduate student Sara Wirtz is
prepping membranes in petri dishes. This involves
spinning cells down and getting rid of all the stuff on
the inside, says Wirtz, so experiments can be performed
solely on the proteins. Beakers of bovine serum, resembling
pitchers of cherry Kool-aid, are used as the medium for growing
team has narrowed the search to a nine amino acid sequence.
But there is much they still dont understand, such as
why some people become addicted and others dont.
seems that, for certain individuals, their brain says, This
is just what I was looking for, and theyre off and
running, Justice says. In others, they think, That
was interesting, and then go and wash the car.
examining early-life risk factors like abuse or neglect, Professor
of Psychiatry Paul Plotsky is attempting to discover the biological
basis for vulnerability to depression, addiction, and other
mental disorders. His studies of baby rats who were repeatedly
separated from their mothers at a young age showed that the
stressed rats had a greater susceptibility to drug and alcohol
early environment clearly contributes to the development of
these disorders, by causing permanent, measurable changes in
brain chemistry, Plotsky says.
opposed to determining an individuals destiny, genes seem
to instead create an envelope of potential outcomes
that are then narrowed by external factors.
the human genome project offers a possible diagnostic avenue
that might one day settle the long-standing debate over whether
certain people are genetically predisposed to abuse drugs or
the newly sequenced human genome, scientists have shown that
humans genetic codes are about 99.9 percent the same.
Individuals carry only about fifty different mutations that
influence their health, making them, for example, more vulnerable
to heart disease or less susceptible to certain types of cancer.
T. Warren, William Patterson Timmie Professor and chair of Emorys
department of human genetics, which occupies the third floor
of the Whitehead Research Building, says genes do seem to play
a role in substance abuse.
we can identify those genes and the variance, that will be both
useful clinically to treat addiction and also potentially to
flag individuals who might be prone to the effects of certain
compounds, Warren says.
in the coming decade, he says, there will emerge a great deal
of new insight into the genetics of addictions.
the genes that influence addiction opens up a lot of possibilities.
Perhaps designer drugs will be developed that will moderate
addictive tendencies. I could envision genetics addiction counseling,
he says. Then again, changing peoples lifestyles
is the hardest thing you can do in medicine. Therell be
gallant efforts, but the outcome is unclear.