BIOLOGY OF
ADDICTION:
What Neuroscience Has to Tell Us
About Addiction as a Brain Disorder
Daniel P Logan, M.D., FACEP, ABAM
Florida Recovery Center
Addiction Medicine, Emergency Medicine
Assistant Professor, Dept. of Psychiatry
University of Florida College of Medicine
ASAM Definition of ADDICTION

“Addiction is a primary, chronic disease of
brain reward, motivation, memory and
related circuitry. Dysfunction in these
circuits leads to characteristic biological,
psychological, social and spiritual
manifestations…addiction often involves
cycles of relapse and remission”
Four Options to Explain Addiction
Brain Disorder
 Matter of Will- “Disorder of Choice”
 Bad Character
 Self Medication

Rectal Cranial Inversion
Moral Weakness or
Stigma View
Why observations make you think
it’s not a disease?

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Looks like weak willed – they should be able to
stop if they put their mind to it
They caused it themselves
Your own experience with being able to stop
drugs successfully
Consequences of use are immoral, sinful and bad
People should be aware that drugs are bad for
them and should not have used them in the first
place
Despite ‘good’ conventional medical, psychiatric
and religious care, addicts get worse
It hurts others
Prejudice – your negative experience
What observations provide
evidence that it is a disease?
They seemed liked such normal people
until they started using drugs
 It tends to run in families
 Not everyone who uses drugs becomes
addicted
 They use compulsively and can’t stop
even with their best efforts
 Has predictable symptoms – they get
worse with time
 Reasonable people would stop under
those conditions
 Some people like drugs and some don’t

ADDICTION IS A DISEASE OF THE BRAIN
As other diseases, it affects tissue function
Decreased Brain Metabolism in Drug Abuse Patient
High
Control
Cocaine Abuser
Low
Healthy Heart
Diseased Heart
Sources: From the laboratories of Drs. N. Volkow and H. Schelbert
VTA
Amphetamines
Opiates
THC
PCP
Ketamine
Nucleus
Nicotine
accumbens
Alcohol
benzodiazepines
barbiturates
Dopamine Pathways
NT
Normal Functions
Dopamine
(pleasure,
learning)
Pleasure (hunger/thirst/sexual),
attention, organization of thought,
muscle control and motor function
Serotonin
(emotional
stability)
Regulates mood, emotions, thought
processes, sleep, and appetite
Norepinephri
ne
(behavioral
& physical
activity)
Energy, motivation, attention span,
alertness, pleasure, assertiveness,
confidence, heart rate, blood
pressure, etc.
Glutamate and GABA
How Drugs of Abuse Effect
Dopamine
Inhibit Reuptake of Dopamine
 Stimulate Dopamine transporter

◦ Cocaine, Amphetamine, Methamphetamine,
XTC

Modulate firing of Dopamine releasing
cells by actions on GABA and Glutamate
◦ Nicotine, alcohol, opiates, cannabis
◦ Cocaine, Amphetamine, Methamphetamine,
XTC
Drugs, Brains,and Behavior: The Science of
Addiction; NIDA, March 2007
Initiation of Addiction

Adolescents
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◦
◦
◦
Risk taking
Novelty seeking
Responsive to peer pressure
Incomplete development of frontal regions
involved in “executive function”
The developing brain……..
What happens when you expose the developing
brain to drugs during adolescence??
Gateway Drug
Adolescent Brain Changes

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Earlier drinking more likely to result in
alcohol dependence independent of
family hx (Grant 1998)
Exposure of alcohol may indeed cause
alterations in brain chemistry…. There
are studies indicating heaving drinking
during adolescence causes memory and
neuropsychological changes (Brown, et
al)
Alternative explanation that early use
may simply be a marker for example
high novelty seeking behavior which is
associated with early use as well as a
risk for alcohol dependence
Adolescent Brain Changes

Animal studies show that early exposure to
alcohol results in longer term problems such
as cognitive and behavioral problems

Stress during adolescence maybe important
factor in causing predisposition to etoh –
adolescents perception of stress was
associated with larger quantities of alcohol
consumption

Remodeling of brain during adolescence –
especially noted in the dopaminergic setting
Genetics
Genes either increase risk or are
protective
 Persistent drug use leads to gene
transcription modification-part of neuroplasticity

◦ Htrlb receptor gene absence greater attraction
to cocaine and alcohol
◦ Curl receptor gene presence makes less
responsive to morphine
◦ ALDH*2 if two copies less likely to develop
alcoholism
Genetics
Twin studies in alcohol
 Sway study of sons of alcoholics
 If have one alcoholic parent 3-4 times
increase risk of alcoholism
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ALLOSTASIS
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Homeostasis feedback-Allostasis “feed
forward”
State of chronic deviation of regulatory
system from normal i.e. homeostasis
“The New Normal”
“I don’t even get high anymore”
Brain adaptation to persistent drug
exposure- NOT the same as tolerance
Tolerance
Tolerance- defined by either of the following:

◦
◦
A need for markedly increased amounts of the
substance to achieve intoxication or desired effect
markedly diminished effect with continued use of
the same amount of the substance
WITHDRAWAL

Withdrawal- the predictable
constellation of signs and symptoms
following the abrupt discontinuation of,
or rapid decrease in, the consumption
of a drug used consistently for a period
of time.
Effects of Withdrawal

Decrease in Dopamine levels
◦ Decrease in response to normally rewarding
stimuli
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Increase in “stress system” elevated CRF
◦ Significant increase in anxiety and dysphoria
Craving

NOT just wanting or liking something
◦ “I’m craving a Starbucks about now”
A MIDBRAIN (limbic system) process
involving both memory and emotion
 Similar to hunger and thirst
 Previously neutral stimuli take on drug
related significance

The Memory of Drugs
Amygdala
Amygdala
not lit up
activated
Front of Brain
Back of Brain
Nature Video
Cocaine Video
"People, places and things..."
RELAPSE
Re institution of drug taking
 Persistence of dysregulation of reward
system

◦ Length of dysfunction related to drug and
person

Triggered by:
◦ Drug re exposure- may be other drug of
abuse- need not be DOC
◦ Emotional state
◦ Stress
Differing Drug Effects
Nicotine appears to have very long lasting
and strong persistence of midbrain
sensitivity to nicotine re-exposure
 Methamphetamine, XTC, bath saltssignificant destruction of neurons both
midbrain and cortex

RECOVERY IS THE ANSWER
Daniel P Logan, M.D., FACEP, ABAM
Florida Recovery Center
Addiction Medicine, Emergency Medicine
Assistant Professor, Dept. of Psychiatry
University of Florida College of Medicine
dlogan@ufl.edu
352.265.5549