New developments in Addiction Medicine

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New developments in Addiction Medicine

• Mark Publicker, MD FASAM
• Medical Director
• Mercy Recovery Center

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Addiction

• a chronic but treatable brain disease
  characterized by
• loss of control
• compulsive use
• use despite known harm
• relapse

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Definition

• Addiction is a cycle of spiraling dysregulation
  of brain reward systems that progressively
  increases, resulting in compulsive drug use and a
  loss of control over drug taking George Koob

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Genetics

• No single gene
• 40 genetic
• Cloningers twin study
• COGA

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Co-morbid psychiatric disorders

• Depression
• Anxiety disorders
• Bipolar disorder

• Schizophrenia
• ADHD
• PTSD
• ASP
• Axis II disorders

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Pathophysiology

• Neural circuitry of reward and brain reward
  thresholds
• Tolerance
• Altered hedonic tone
• Sensitization
• Activation of HPA axis
• Genetic predisposition

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Neural circuitry of reward

• Present in all animals
• Produces pleasure for behaviors needed for
  survival
• Eating
• Drinking
• Sex
• Nurturing

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Self-stimulation studies
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All drugs of abuse bind to the neural circuitry
of reward
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All drugs abuse increase dopamine in the nucleus
accumbens

• alcohol
• cocaine
• heroin
• marijuana
• nicotine

• amphetamines
• sedatives
• hallucinogens
• pcp
• caffeine

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Drugs of abuse hijack the Reward Center

• Instead of eating, drinking and making love,
  drugs tell you that you need to take them in
  order to survive.
• This is obviously a lie, and one that leads to
  sickness and death.

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Neuroadaptation

• Drugs change the brains balance
• The brain has mechanisms to oppose this change
• The balancing action overshoots
• The stronger the drug, the higher the dosage and
  the longer the use, the more the opposing change

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Neuroadaptation alcoholism

• Long term adaptive changes to the inhibitory
  GABAergic system and to the excitatory
  glutamatergic systems are thought to underlie the
  development and maintenance of alcohol dependence

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Neuroadaptation alcoholism

• To compensate for the sedative effects of alcohol
  there occurs an up-regulation of the excitatory
  system and a down-regulation of the inhibitory
  system

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Neuroadaptation alcoholism

• In withdrawal the CNS is left in a hyperexcitable
  state
• anxious
• sleepless
• tremulous
• tachycardic/hypertensive

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Neuroadaptation alcoholism

• Sustained unregulation of the glutamatergic
  system increases the sensitivity to
  context-driven stimuli on the mesocorticolimbic
  dopamine system
• Craving

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Cocaine and mood changes
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Opponent process theory
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Opponent process - heroin
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Allostasis

• Change to new, vulnerable state
• Deficit states inhibition of brain reward
  circuitry
• Altered hedonic tone (Koob)
• Reward thresholds increase
• Opponent process theory
• Counteradaptive hedonic dysregulation

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Cocaine PET scan
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SPECT scan healthy brain top down and underside
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Heroin SPECT scans
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Alcohol
Intoxication
Sober 30 days
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Neuroadaptation - alcoholics drink

• to get high
• to get sedated
• to get numb

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Neuroadaptation alcohol

• high depressed
• sedated anxious/sleepless
• numb anguish/pain

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Positive reinforcers

• Euphoria
• Sedation
• Anesthesia (numbing)

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Negative reinforcers

• Depression
• Anxiety
• Insomnia
• Boredom
• Loss of pleasure

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Volkow methamphetamine

• Persistent reductions in dopamine transport in
  striatum
• Long-term psychomotor impairment

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Medications

• Naltrexone (Revia)
• Topiramate
• Acamprosate
• Methadone
• Buprenorphine
• Antabuse

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Methadone

• Abstinence rates 70-80
• Blocks craving
• Blocks euphoria
• Normalization of HPA axis
• Normalization of limbic function

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Methadone

• Rejection of disease concept
• substitution of one addictive drug for another."
• drug-free state is only valid treatment goal.
• research has shown that this is not achieved nor
  sustained by the majority of heroin addicts.

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Methadone

• Death rates of patients not on mmt three times
  those on mmt
• Reduction in hiv seroconversion from 50 to 2.5
  of IVDA
• 95 prevalence Hepatitis C in chronic IVDA

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Buprenorphine/naloxone Suboxone

• Partial agonist pure antagonist
• t/2 24 hours
• Blocks craving and euphoria
• Less physical dependence
• Combo decreases diversion risk

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Suboxone

• DATA 2000 can be prescribed by office-based
  physicians
• DEA waiver
• 30 patient limit
• Adolescent/young adults

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Therapeutic effects

• Blocking effect on euphoria with administration
  of heroin
• Blocking effect on withdrawal.
• Relieves craving
• Stabilization of brain function
• Decrease in HPA stress state
• Improvement in mood and behavioral stability

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Revia - Naltrexone

• Pure opioid antagonist
• Effective in treatment of alcoholism and opiate
  addiction
• Blocks craving
• Blocks the high and increases the negatives

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Acamprosate

• NMDA receptor antagonist
• Blocks craving
• Doubles abstinence rates
• Additive with naltrexone

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Topiramate

• Anti-convulsant glutamate antagonist
• Anti-craving agent for alcohol, cocaine and
  cannabis
• Increases alcohol abstinence rates by 50
• Patients reports enhanced sense of well-being

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Antabuse

• Oldest drug treatment for alcohol dependence
  through blockade of aldehyde dehyrogenase
• Limited double-blind, placebo controlled studies
• New role treatment of cocaine dependence

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Antabuse

• Cocaine mechanism separate from disulfiram effect
• Studies show enhanced abstinence especially with
  combination of cognitive behavioral therapy with
  disulfiram
• Decreased craving and increased dysphoria with
  cocaine use

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On the horizon

• Baclofen GABA agonist
• Ondansetron
• Sodium oxybate
• Modafinil
• Cocaine vaccine
• GVG

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Summary

• Addiction is a treatable brain disease
• Research is edifying the biological mechanisms
  involved
• Increased understanding of neurobiology is
  allowing for the development of effective,
  targeted pharmacotherapies