BIOLOGY OF ADDICTION:

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BIOLOGY OF ADDICTION

• What Neuroscience Has to Tell Us About Addiction
  as a Brain Disorder

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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
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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 manifestationsaddiction often
  involves cycles of relapse and remission

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Four Options to Explain Addiction

• Brain Disorder
• Matter of Will- Disorder of Choice
• Bad Character
• Self Medication

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Rectal Cranial Inversion
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Moral Weakness or Stigma View
weak willed
bad
irresponsible
depressed
immoral
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Why observations make you think its not a
disease?

• 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

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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 cant 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 dont

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ADDICTION IS A DISEASE OF THE BRAIN As other
diseases, it affects tissue function
Diseased Heart
Healthy Heart
Sources From the laboratories of Drs. N. Volkow
and H. Schelbert
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VTA
Amphetamines Opiates THC PCP Ketamine Nicotine
Alcohol benzodiazepines barbiturates
Nucleus accumbens
Dopamine Pathways
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NT Normal Functions

• Dopamine (pleasure,
  
  
  learning)
• Serotonin (emotional stability)
• Norepinephrine
• (behavioral physical activity)

• Pleasure (hunger/thirst/sexual), attention,
  organization of thought, muscle control and motor
  function
• Regulates mood, emotions, thought processes,
  sleep, and appetite
• Energy, motivation, attention span, alertness,
  pleasure, assertiveness, confidence, heart rate,
  blood pressure, etc.

Glutamate and GABA
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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

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Drugs, Brains,and Behavior The Science of
Addiction NIDA, March 2007
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Initiation of Addiction

• Adolescents
• Risk taking
• Novelty seeking
• Responsive to peer pressure
• Incomplete development of frontal regions
  involved in executive function

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The developing brain..
What happens when you expose the developing brain
to drugs during adolescence??
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Gateway Drug
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Adolescent Brain Changes

• 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

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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

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Genetics

• Genes either increase risk or are protective
• Persistent drug use leads to gene transcription
  modification-part of neuro-plasticity
• Htrlb receptor gene absence greater attraction to
  cocaine and alcohol
• Curl receptor gene presence makes less responsive
  to morphine
• ALDH2 if two copies less likely to develop
  alcoholism

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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

• Homeostasis feedback-Allostasis feed forward
• State of chronic deviation of regulatory system
  from normal i.e. homeostasis
• The New Normal
• I dont even get high anymore
• Brain adaptation to persistent drug exposure- NOT
  the same as tolerance

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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

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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.

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Effects of Withdrawal

• Decrease in Dopamine levels
• Decrease in response to normally rewarding
  stimuli
• Increase in stress system elevated CRF
• Significant increase in anxiety and dysphoria

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Craving

• NOT just wanting or liking something
• Im 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

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The Memory of Drugs
Amygdalanot lit up
Amygdalaactivated
Front of Brain
Back of Brain
Nature Video
Cocaine Video
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"People, places and things..."
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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

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Differing Drug Effects

• Nicotine appears to have very long lasting and
  strong persistence of midbrain sensitivity to
  nicotine re-exposure
• Methamphetamine, XTC, bath salts- significant
  destruction of neurons both midbrain and cortex

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RECOVERY IS THE ANSWER
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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_at_ufl.edu 352.265.5549