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Staying Sober |
| Better understanding of
how alcohol alters brain chemistry reveals mechanisms for
beating dependency |
| By Andreas Heinz |
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Former alcoholics have a tough time resisting the urge to
drink in two particularly trying situations. Analysis of
what is happening in their heads under these circumstances
is greatly improving neurobiologists' understanding of how
chronic alcohol use changes the brain. And their findings
suggest measures that could help people abstain.
The following case illustrates one of the most tempting
situations. Hank had been dry for several weeks thanks to
a radical withdrawal program, but a simple walk past
Pete's Tavern on any given night almost erased his will to
abstain. During the daytime he did not feel a craving for
alcohol, but when he passed the bar in the evening--when
he saw the warm light through the windows and heard the
glasses clinking--he would be sorely tempted to run inside
for a beer. Addiction researchers call this phenomenon
"conditioned desire." If a person had always consumed
alcohol in the same situation, an encounter with the
familiar stimuli will make the feeling of need for the
substance almost irresistible. Then, even after years of
abstinence, consuming a single drink can set off a
powerful longing to imbibe more and more. |
| Ken's story illustrates the other common
temptation. Ken had given up alcohol and was doing fine,
even after he had lost his job and had begun collecting
unemployment. But on one visit to the unemployment office
downtown, a bureaucrat refused to approve his benefits.
After a fruitless argument, Ken left. While standing on
the subway platform for a train home, he suddenly began to
sweat, twitch and feel sick. What he really wanted was a
bottle. Before he had given up drinking, he would have
automatically taken a swig whenever he faced a tense
situation. After the argument, his brain--shaped by
experience--expected the calming effect of alcohol. When
the drug did not come, he began to suffer what experts
call "conditioned withdrawal" symptoms.
The very people who can drink
others under the table are the ones who are especially at
risk. The very people who can drink others under the table
are the ones who are especially at risk.
Conditioned desire and conditioned withdrawal are
produced in the brain by different mechanisms. In recent
years, neuroscientists have investigated both phenomena
thoroughly. They now feel comfortable explaining how
routine alcohol consumption changes circuitry in the brain
in ways that lead to addiction, and they are beginning to
develop new medications that could dramatically reduce the
chances of falling off the wagon.
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High Tolerance Is Bad
For centuries, societies have labeled alcoholics as
self-indulgent people who lack willpower. Although the
decision to drink in the first place does rest with each
individual, traits inherent in a person's brain cells can
strongly influence the slippery slope into addiction.
Furthermore, once a person is addicted, simple willpower
may be insufficient to break the grip; drugs that can
reverse the brain's alcohol-altered chemistry may be
necessary.
An individual's sensitivity to alcohol's effects on
neurons significantly influences the chance that he or she
can become addicted. According to Marc A. Schuckit, a
psychiatry professor at the University of California, San
Diego, and director of the VA San Diego Healthcare
System's Alcohol and Drug Treatment Program, one of the
best protections against addiction is nausea; people who
readily get sick as they drink are less likely to consume
enough, consistently, to the point that they become
addicted. The very people who can drink others under the
table are the ones who are especially at risk. Inhibitory
and excitatory messenger substances in the brain become
unbalanced in response to excessive alcohol doses. The
people who can handle more drinking send more alcohol to
the brain, thereby increasing over time the chance that a
permanent imbalance will develop.
This brain chemistry was partially worked out in rhesus
monkeys that had to grow up without their mothers, some in
the laboratory and some in the wild. James Dee Higley, a
research psychologist at the National Institute on Alcohol
Abuse and Alcoholism, learned that these monkeys reacted
less to drinks of high-proof alcohol than normal monkeys
did. The motherless monkeys were similarly insensitive to
other substances that, like alcohol, increase the impact
of the neurotransmitter GABA (gamma aminobutyric acid),
which inhibits signals between neurons so the cells do not
get overexcited. |
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| As a result of this reduced sensitivity, the
rhesus monkeys raised in isolation could drink an unusually
large quantity of alcohol--and they sought to do so when
researchers provided free access to the drug. Human studies
have revealed similar changes in people's brains.
Altered brain chemistry resulting from experience is just
one factor that contributes to individual differences in
susceptibility. Genes play a role, too. Schuckit maintains
that up to half the causal factors for reduced sensitivity to
alcohol are inherited. In a small-scale study that tracked
people for 15 years, Schuckit's research group found that a
variation in the gene that codes for a part of the GABA
receptor may be related to low sensitivity to alcohol. |
| Although high tolerance to alcohol from
adjusted brain chemistry or genetics may seem like a
protective trait, it is ultimately damning. If such an
individual consumes quantities of alcohol regularly, his or
her brain and body will gradually become accustomed to the
poison, almost assuring the person will become addicted.
Dangerous Accommodation
Tinkering with the GABA system could perhaps offer a fix, but
alcohol's effects on brain chemistry depend on more than just
GABA uptake. The drug does not merely boost the inhibitory
function of GABA on neurons; it also blocks the excitatory
effects of their NMDA (N-methyl-d-aspartate) receptors. These
receptors bind glutamate, which comes from neighboring neurons
and enables the receiving neuron to forward signals on to
others in the network. Guochuan Tsai, now at the University of
California, Los Angeles, and Joseph T. Coyle of Harvard
Medical School have discovered that the brain, when exposed to
chronic alcohol consumption, creates additional NMDA receptors
to compensate for the blocking effect [see box on preceding
page]. The brain is trying to find a new balance between the
underexcitatory action of glutamate and the overinhibitory
action of GABA.
The repercussions come, however, when alcohol is withdrawn
for a few days or, for hard-core drinkers, even overnight. The
NMDA receptors maintain their increased sensitivity, and the
GABA receptors maintain their reduced sensitivity. Yet without
the alcohol that this new balance is attempting to counter,
the brain's networks fire erratically, causing withdrawal
symptoms. Anyone who wakes up with tremors, sweating or nausea
and immediately needs alcohol is already critically dependent.
The victim's brain is so utterly adapted to the drug that even
the few nighttime hours without it are enough to throw the new
chemistry into a tailspin.
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| Such withdrawal symptoms can be combated with
agents such as chlormethiazol or a benzodiazepine, which
restore the sensitivity of GABA receptors and calm the
patient. Acamprosate suppresses NMDA receptors and seems
especially helpful for persons suffering from conditioned
withdrawal. Clinical studies show that 30 to 40 percent of
patients remain dry for the first year after detoxification
while taking acamprosate. The drug is particularly effective
during the first few hard months of abstinence, when relapse
rates are the highest. The results still leave a high failure
rate, however, necessitating additional therapeutic measures
such as self-help groups and individual counseling.
Drugs can reduce the alcoholic
brain's oversensitivity to glutamate and oversupply of
dopamine.
One reason medication can be insufficient is that alcohol
also works on dopamine, the neurotransmitter that runs the
motivation and reward system. Normally, stimuli that are
important to survival--related, for example, to feeding and
sex--trigger the release of dopamine. The neurotransmitter
increases our anticipation of happiness and makes us want
these things. The pleasant reward feelings, in turn, make us
seek the sensations again and again, and we engage more
strongly in the behaviors that cause dopamine to be released.
Addictive drugs such as heroin unleash the same mechanisms.
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| As it does for GABA and NMDA, brain chemistry
related to the reward system also adapts to fit the constant
presence of alcohol. The brain reduces the number of dopamine
binding sites on neurons, called D2 receptors, to protect
itself from a persistent oversupply of the neurotransmitter.
Alcohol affects other aspects of the motivation system as
well. When alcoholics look at photographs of beer or wine, the
regions of their brain that control attention are aroused more
than they are for nonalcoholics, according to MRI imaging
studies done in my lab. The fewer the D2 receptors they have,
the more activity is elicited in their attention centers by
the sight of alcohol.
This predilection explains why it is so difficult for
alcoholics to find other stimuli pleasant and rewarding. It
seems almost impossible for them to become interested in
anything new that might bring satisfaction--be it a
relationship, a hobby or even good food. The more serious the
damage to the dopamine system, the more fixated attention
becomes on the familiar images of alcohol--even when the
person is lying inside the narrow, noisy tube of an MRI
machine, when the brain knows it is not about to receive beer
or whiskey. |
| The extent to which the attention centers can
be activated in this lab situation highlights the severe
problems recovering alcoholics have ignoring the advertising
all around them. About a third of the subjects in our studies
complain about the powerful effects of television commercials,
especially when they are broadcast in situations in which
patients would previously have been drinking, such as while
watching a football game.
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Tainted Pleasure
Although dopamine directs desire, the actual feeling of
pleasure comes from endorphins--the body's own opiatelike
substances. Once again, regular drug use changes the system.
Alcoholics develop a higher number of binding sites for
endorphins. When they drink, their neurons bind more
endorphins, producing a greater feeling of pleasure.
Certain medications have been designed to alter this
interchange. Naltrexone, for example, blocks the receptors and
can reduce the risk of relapse considerably. Recovering
alcoholics say that if they are taking naltrexone and have a
drink, the taste is foreign, to the point of being terrible.
Yet the drug alone, without psychosocial care, is not enough,
because for some patients the second or third drink will start
to taste good again. A patient must want to live abstinently;
then, naltrexone will help him or her avoid that first sip.
With the expanding understanding of how alcohol alters the
action of neurotransmitters, it is becoming clear that people
addicted to alcohol are suffering from dramatic changes in
brain activity. No particular personality type is prone to
becoming dependent. The culprit is excessive alcohol
consumption itself, which changes the brain so that victims
can no longer free themselves from the bottle. It is time to
destigmatize alcoholism and to develop better methods of
breaking dependency and preventing relapse. The knowledge
gained from research certainly opens avenues for creating new
drugs. Still, alcoholics need one aid above all: people who
will listen to and stand by them as they strive to recover.
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Hearts of Hope
P.O. Box 3314
St. Charles, IL 60174
Tel: (630) 327-9937
Fax: (630) 232-9240
Email: Info@HeartsOfHope.Net
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