Transcript The Neurobiology of Addiction - Medical University of South Carolina

Basics on Alcohol
Steven D. LaRowe, Ph.D.
Center for Drug and Alcohol Program
Medical University of South Carolina
Substance Abuse Treatment Center
Ralph H. Johnson VAMC
Alcohol is “tricky”
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Many people drink, but only a few qualify has
having a diagnosis of abuse or dependence
Most “budding” alcoholics want to continue to
drink, or control drinking
AA disease model = you’ll never drink again
Some patients will resist that and will turn away
from treatment
Hard to know who is the person who will drink
responsibly in the future, or who will never be
able to again
Need to “roll with this resistance”
What is moderate drinking?
Men: no more than 4 drinks per day
 Men: no more than 14 drinks per week
 Women: no more than 3 drinks per day
 Women: no more than 7 drinks per week
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How many people drink?
 18
and over, between 40 and
70% drink
 Heavy drinkers: between 5
and 20%
 Rates of Dependence: 7%
young adults (18-25), 3% for
those over 26
Basic Wiring of the Brain
DSM-IV: Alcohol Abuse
1 or more within a 12-month period:
 Drinking results in failure to fulfill major role
obligations at work, school, or home
 Drinking in situations in which it is physically
hazardous
 Recurrent alcohol-related legal problems
 Drinking despite social/interpersonal
problems
 These symptoms must never have met the
criteria for alcohol dependence.
DSM-IV: Alcohol Dependence
3 or more in the same 12-month period:
 Tolerance:
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Withdrawal:
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Either need more to effect OR experience markedly diminished
effects
Either withdrawal syndrome for alcohol or drink to avoid the
syndrome
Drinking more over a longer period than was intended.
Desire/unsuccessful efforts to cut down/control use.
Excessive time is spent in obtaining, using or recovering
from alcohol
Reduced social, occupational, or recreational activities
b/c drinking
Continue to use it even though it causes physical or
psychological problems
The 3-stage progression of addiction
Recall: Learning occurs
quickly when using
alcohol/drugs – change
in gene expression is
involved. Genes
determine protein
structure, structure of
protein determines
function, etc.
Source: Kalivas & Volkow, 2005)
Abuse
Time to develop ETOH dependence
Dependence
5 to 10 year progression
Biological Action of Alcohol
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GABA – neurotransmitter involved in
inhibition – is increases by alcohol
Glutamate – neurotransmitter involved in
excitation, memory (NMDA is a type of
glutamate receptor) – is inhibited by
alcohol
Alcohol indirectly causes release of
dopamine, presumably through effects on
GABA, which regulates dopamine release
Alcohol going in and out
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“Biphasic” meaning “two phases”
As alcohol levels increase, dopamine is
released, people feel good (a.k.a. the
“ascending limb”
Peaks about an hour after last drink on empty
stomach, longer if you’ve eaten (2 hours)
(Warning: people doing shots can do a bunch in
a few minutes, and feel “OK” and leave, but the
real intoxication is yet to come)
After alcohol levels peak, they start to decrease
and sedative effects are most notable (a.k.a. the
“descending limb”
Source: King et
al. 2002
Drinks, BAL, and effects
BAC Table for Men
Body Weight in Pounds
Drinks
100 120 140 160 180 200 220 240
Condition
Only Safe
Driving
Limit
0
.00
.00
.00
.00
.00
.00
.00
.00
1
.04
.03
.03
.02
.02
.02
.02
.02
2
.08
.06
.05
.05
.04
.04
.03
3
.11
.09
.08
.07
.06
.06
.05
Driving
Skills
.03
Significantly
Affected
.05
4
.15
.12
.11
.09
.08
.08
.07
.06
5
.19
.16
.13
.12
.11
.09
.09
.08
6
.23
.19
.16
.14
.13
.11
.10
.09
7
.26
.22
.19
.16
.15
.13
.12
.11
8
.30
.25
.21
.19
.17
.15
.14
.13
9
.34
.28
.24
.21
.19
.17
.15
.14
Criminal
Penalties
10
.38
.31
.27
.23
.21
.19
.17
.16
Death
Possible
Possible
Criminal
Penalties
Legally
Intoxicated
Subtract .01% for each 40 minutes of drinking.
1 drink = 1.25 oz. 80 proof liquor, 12 oz. beer, or 5 oz. wine
Source: http://www.alcohol.vt.edu/Students/alcoholEffects/estimatingBAC/index.htm
Drinks, BAL, and effects
BAC Table for Women
Body Weight in Pounds
Drinks 90 100 120 140 160 180 200 220 240
Condition
Only Safe
Driving
Limit
0
.00 .00
.00
.00
.00
.00
.00
.00
.00
1
.05 .05
.04
.03
.03
.03
.02
.02
.02
2
.10 .09
.08
.07
.06
.05
.05
.04
3
.15 .14
.11
.10
.09
.08
.07
.06
Driving
Skills
.04
Significantly
.06
Affected
4
.20 .18
.15
.13
.11
.10
.09
.08
.08
5
.25 .23
.19
.16
.14
.13
.11
.10
.09
6
.30 .27
.23
.19
.17
.15
.14
.12
.11
7
.35 .32
.27
.23
.20
.18
.16
.14
.13
8
.40 .36
.30
.26
.23
.20
.18
.17
.15
9
.45 .41
.34
.29
.26
.23
.20
.19
.17
10
.51 .45
.38
.32
.28
.25
.23
.21
.19
Possible
Criminal
Penalties
Legally
Intoxicated
Criminal
Penalties
Death
Possible
Subtract .01% for each 40 minutes of drinking.
1 drink = 1.25 oz. 80 proof liquor, 12 oz. beer, or 5 oz. wine.
Source: http://www.alcohol.vt.edu/Students/alcoholEffects/estimatingBAC/index.htm
When the party’s over
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“Rebound” occurs when alcohol clears
Now, glutamate makes a comeback
In persons not tolerant to alcohol it can disturb
sleep
Chronic exposure to alcohol leads to changes in
GABA. Body makes less of it, so when its gone,
Glutamate rules the day
Lots of Glutamate activity  CNS activation 
withdrawal symptoms = shakes, anxiety, and
extreme cases, seizures and Delerium Tremens
Tolerance
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Functional: you function even when others
would be severely impaired if they drank the
same amount
Tolerance does not develop equally across all
domains (e.g. OK mental functions, but still
impaired coordination)
Environment dependent tolerance – tolerance in
one place but not another
Liver can speed up, but this can cause it to
process other things (like other meds) too
quickly
(Source: NIAAA Alcohol Alert 28)
Special Concern: Alcohol
Withdrawal
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Can have severe, even deadly, result, if
untreated
Therefore, you need to have some idea whether
you client is at risk
Can begin within a few hours of cessation of
drinking
Can last up to 72 hours
“Kindling” theory – the more withdrawals you
have, the more risk of seizures
Seizures can be damaging, and if you have one,
you are more at risk for another
DSM-IV: Alcohol Withdrawal
2 (or more) of the following, developing within several
hours to a few days after alcohol cessation/reduction:
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autonomic hyperactivity (e.g., sweating or pulse
rate greater than 100)
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increased hand tremor
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insomnia
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nausea or vomiting
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transient visual, tactile, or auditory hallucinations or
illusions
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psychomotor agitation
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anxiety
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grand mal seizures
Screening for Alcohol problems
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1.
2.
3.
4.
CAGE: Two "yes" responses indicate that the
respondent should be investigated further. The
questionnaire asks the following questions:
Have you ever felt you needed to Cut down on
your drinking?
Have people Annoyed you by criticizing your
drinking?
Have you ever felt Guilty about drinking?
Have you ever felt you needed a drink first
thing in the morning (Eye-opener) to steady
your nerves or to get rid of a hangover?
Know what “Standard Drink” Is
12 oz. of
beer or
cooler
8-9 oz. of
malt
liquor
8.5 oz. shown in a 12-oz.
glass that, if full, would hold
about 1.5 standard drinks of
malt liquor
5 oz.
of
table
wine
3-4 oz.
of
fortified
wine
(such as sherry or port)
3.5 oz. shown
2-3 oz.
of
cordial,
liqueur
or
aperitif
1.5 oz.
of
brandy
(a single jigger)
1.5 oz. of
spirits
(a single jigger of 80-proof gin,
vodka, whiskey, etc.) Shown
straight and in a highball glass
with ice to show level before
adding mixer*
2.5 oz. shown
12 oz.
8.5 oz
5 oz.
3.5 oz.
2.5 oz.
1.5 oz.
1.5 oz.
•People will count a 24 oz. “tall boy” beer as 1 beer – it’s more like 2
•People will make a drink with several shots (“double, triple”, and count
it as 1 drink
•One client told me she had “3 drinks” last night, but I found out later
that each was a mixed drink with 5 shots of vodka each!
Source: A Pocket Guide for Alcohol Screening and Brief Intervention, NIAAA
Quick Alcohol Withdrawal
Questions
Questions to ask:
 Ask if they’ve ever been “detoxed” for alcohol
 Ask about withdrawal symptoms (shakes,
sweats)
 Ask about number of previous withdrawals
they’ve gone through
 If in private practice, cultivate a relationship with
a psychiatrist or other medical practitioner
CIWA
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Clinical Institute Withdrawal Assessment
At the VA, we have a “CIWA protocol”
Essentially, the medical people assess
withdrawal over time
Treatment for withdrawal has traditionally been
benzodiazepines (e.g. Valium, Ativan)
We are trying to use anti-seizure medications
(e.g. Gabapentin, Carbemazepine), because
they are not cross-tolerant to alcohol (and less
addictive)
Click here for a copy of the CIWA
What I look for when assessing a
drinker
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When did drinking
begin?
How many years of
heavy drinking?
How many standard
drinks per day?
Do you ever have
just one or 2 drinks?
How many times in
treatment?
# of Charges for
DUI’s, drunk and
disorderly
(CHARGES not
convictions, in case
they took a plea)
Among people over 21, those who with
dependence are more likely to have started
drinking before the age of 14 (8%) than age 21
(1%). Alcohol dependence develops over 5-10
years, so if drinking has occurred longer than that,
dependence more likely
People who exceed both daily/weekly limits
have a 50% chance of abuse/being
dependent
Can they stop? If no, possibly they have
become compulsive drinkers. More
treatment attempts = more likely they
have serious dependence (compulsive)
problem
Objective evidence of problems
More things I look for
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As part of your standard intake, you’ll have
gotten family, work, medical histories.
Keep these in mind, as problems in these
areas are often alcohol-related but not seen
as such by the drinker!
 You might be able to make that link in
sessions to help increase your motivation.
 However, it is important to ask the patient
what she/he sees as being problems cause
by alcohol
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Using your BAL monitor
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We typically have used BAL monitor for
individual therapy in research
We have them on hand at VA
They are always useful, but a patient might not
show up if he/she thinks she might come up
positive
Things to watch for when patients come up
positive…(e.g. they will come up positive and
still deny using)
Some cough syrups make people come up
positive – not an excuse though!
Biological indicators of drinking
Clinical issues
Is this a person who can never, ever drink
again or might this be someone who can
moderate?
 There are a number of people who
“spontaneously” remit, and stop drinking
on their own (as high as 30%)
 On the other hand, if they could have
remitted, would they be here for
treatment? (Maybe, maybe not)
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Abstinence versus Moderation
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The more evidence for dependence (e.g. older
age, longer drinking time, more failed
treatments), elevated liver leves, the more I
might guide client towards goal of complete
abstinence
Younger age, less time drinking, controlled
drinking might be more acceptable goal
In general, however, even if patient wants
controlled drinking, I will suggest that it works
better after an extended period of abstinence
(based on clinical experience, no empirical
evidence in my possession so far)
Abstinence vs. Moderation
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Many times, I will think the patient in no way can
handle drinking, yet patient insists on trying
controlled drinking
I will negotiate with them a weekly and daily limit
(start low, below recommended levels, the
patient argues us)
I will then have patient track drinking (educate
about standard drinks), and see if they can keep
limits
If patient can’t keep limits, then we revisit
abstinence
Activity
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Create a client, complete with drinking history.
Decide the extent to which client is aware of
their problem.
Recognize that some people will report
problems but not see them related to drinking
Recognize that many people are in treatment at
someone else’s behest
Recognize the tendency to minimize and
underreport problems