The Corpus Callosum

Why
is it that recovering persons with alcoholism should not drink
near-beer (beer with little or no alcohol)?  

…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… ( href="http://www.sciammind.com/article.cfm?articleID=000DE85A-5630-1429-898483414B7F0000&pageNumber=1">link)


Is this real?  How does this work?

First, is this real?  On a list of href="http://webpages.charter.net/jlbond/slogans.htm">AA
slogans, #298 (out of 407) is “Don’t hang around wet places
and wet faces.”  (I’m sure there are many variations.)
 There is a reason it has become a slogan.  Several
reasons, actually.  From href="http://www.nature.com/neuro/journal/v8/n11/full/nn1579.html">Neural
systems of reinforcement for drug addiction: from actions to habits to
compulsion
[Barry J Everitt & Trevor W
Robbins, Nature Neuroscience 8, 1481 - 1489 (2005)]

href="http://scienceblogs.com/corpuscallosum/images/addiction_neural_cicuits.gif">i-48b629feea9dab4b01c8570ce48d33a9-addiction_neural_cicuits_500px.jpg

Click image for full size, non-compressed (more readable)
version


So
yeah, it is real.  That leaves the question of how it works.
 We need to understand both conditioned desire, and (even more
intriguing), the phenomenon of  href="http://www.who.int/substance_abuse/terminology/who_lexicon/en/print.html">conditioned
withdrawal

…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…


In order to understand conditioned desire and withdrawal, we need to
understand what alcohol does to the brain, and what alcohol withdrawal
does.

i-5d9540cfbda9f0e34a26863a8ac10b95-200px-Gamma-Aminobuttersäure_-_gamma-aminobutyric_acid.svg.pngThe href="http://pubs.niaaa.nih.gov/publications/arh22-1/13-24.pdf">mechanism
for alcohol withdrawal (PDF) is well-known.  Alcohol
boosts the effect of href="http://en.wikipedia.org/wiki/Gamma-aminobutyric_acid"
rel="tag">GABA (primarily at
the GABAa receptors).
 GABA (image to left) is the most abundant inhibitory
neurotransmitter in the
human brain.  It is like the brake on an automobile.
 Chronic consumption of alcohol causes the brain to adapt.
 One of the adaptations is to cut back on the production of
GABA.  That is like putting your foot on the accelerator.
 So if someone drinks a lot and develops tolerance to the
alcohol, it is like they have one foot on the accelerator and one on
the brake.  If they stop drinking, it is like taking the foot
off the brake, leaving a foot on the accelerator.  The neural
activity in the brain accelerates
rapidly, and the person develops href="http://www.aafp.org/afp/20040315/1443.html">symptoms
of alcohol withdrawal.  

i-1865f28d24b84b88b8b5a27da70a9d55-200px-Dopamine2.svg.pngNote
that the mechanism presented above is an oversimplification.
 There are other systems involved, primarily
and calcium
channels
.   href="http://en.wikipedia.org/wiki/Dopamine">Dopamine
(image to right) is involved as well.  Check the first link in
the paragraph
above for details.

The mechanism for alcohol withdrawal is reasonably straightforward, but
the mechanism for conditioned withdrawal is not so simple.
 From href="http://pubs.niaaa.nih.gov/publications/arh22-1/25-34.pdf">Kindling
in Alcohol Withdrawal
(PDF) [Howard C. Becker,
Ph.D., Alcohol Health & Research World, Vol. 22, No. 1, 1998]

During
a conditioned withdrawal response,
environmental stimuli that are repeatedly associated with withdrawal
symptoms (e.g., a physician’s office or hospital) may
themselves become cues that trigger the neurochemical changes resulting
in the physical and psychological withdrawal symptoms. Conditioned
withdrawal related responses, which reflect a kindlinglike process, may
represent the biological basis for cue-induced alcohol craving in these
circumstances…

…AW activates the HPA axis, and the levels of hormones secreted by
the adrenal cortex (i.e., corticosteroids) increase. Research indicates
that this withdrawal-induced increase in corticosteroid levels is
enhanced and more sustained in animals with a history of multiple
withdrawal episodes (Becker and Littleton 1996). One group of
corticosteroids, the glucocorticoids, influence neural excitability by
interacting with certain receptors in the brain. Prolonged stimulation
of these receptors as a result of elevated glucocorticoid levels in the
blood may not only alter seizure susceptibility but also may produce
neural damage, particularly in brain structures such as the
hippocampus…


In other words, the conditioning mechanism is similar to the mechanism
of
posttraumatic stress disorder ( title="Neuroimaging findings in post-traumatic stress disorder"
href="http://bjp.rcpsych.org/cgi/content/full/181/2/102">1,
title="Posttraumatic Stress Disorder (Focus - The Journal of Lifelong Learning"
href="http://focus.psychiatryonline.org/cgi/content/full/1/3/247#SEC3">2,
href="http://trots.blogspot.com/2004/07/ptsd-among-american-service-personnel.html">3).
 So the slogan “Don’t hang around wet places and wet faces”
has a biological substrate.  If you drink a lot, and
especially if you’ve been in withdrawal a lot, your brain gets wired to
have conditioned desire and conditioned withdrawal responses.
 Alcoholics with a bit of experience — or education — know
this.  They know that they shouldn’t drink near-beer for the
same reasons they should avoid other reminders of drinking alcohol.

Comments

  1. #1 Gork
    June 9, 2007

    Aha. This explains a lot.

    You’ve just made me change my politics. Now I want George Bush to go back to cocaine and whiskey.

    Then we can bring our troops home and begin the decade of repair that will be needed.

  2. #2 Drugmonkey
    June 10, 2007

    It may also be the case however that repeated exposure to the cues without the usual outcome (intoxication) will habituate the individual to the cue, thereby decreasing its power to trigger relapse. In some senses the animal reinstatement models do this because the animal is habituated (extinguished) to several cues (operant box, lever responding) but not others (light, tone, etc) which predict drug availability.

  3. #3 Joseph j7uy5
    June 10, 2007

    I am pretty sure that habituation to cues was tried in some treatment centers, and they gave up, because it did not seem to help. perhaps they were not doing it right. Perhaps they need to do it while taking d-cycloserine. Perhaps it works for some people and not others. Humans are like that.

  4. #4 loranarcher
    June 10, 2007

    Excellent review of neurobiology of addictions. I have posted a link to your comments on http://www.alcoholreports.blogspot.com.

  5. #5 Renaisauce
    June 11, 2007

    What about the negative reinforcement of cues, such as inducing nausea in the presence of a bar or a bottle to make the thought of drinking physically awful? I’m sure there’s a lot of negative effects already linked to alcoholism, or else people wouldn’t want to stop, but is there away to make the previous cues completely repulsive?

  6. #6 Drugmonkey
    June 11, 2007

    The first pharmacotherapy for alcohol abuse, Antabuse (disulfiram) was approved in ca. 1951 and takes precisely this approach although it requires actually drinking alcohol to work. It works by blocking a second step metabolism of alcohol, building up a nausea-inducing metabolite (acetaldehyde) formed from initial metabolism.

    This would be “positive punishment”, not “negative reinforcement” btw.

  7. #7 Deepak
    February 7, 2009

    Approximately 95 percent of people who quit drinking alcohol experience mild to moderate withdrawal symptoms and can usually be treated by healthcare providers on an out-patient basis, but five percent experience severe withdrawal symptoms and must be treated in a hospital or a facility that specializes in detoxification.

  8. #8 Sydney
    February 23, 2009

    Now a days it’s a very critical issue as we all are aware by this issue but we are unable to do something about these types of issues. Mostly youngsters are having alcohol and other types of drugs. I think we should think about these types of issues otherwise our coming generation will have to face lot’s of problems. Great Post i look forward to reading more.
    Sydney
    Alcoholism Information

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