ADDICTION SCIENCE

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ADDICTION SCIENCE EVIDENCE BASED
TREATMENTBYDavid L. Ohlms, M.D.
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• THE MORALISTIC ERA
• Addict viewed as either a sinner or a criminal or
  both

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• THE MORALISTIC ERA
• THE FREUDAN ERA
• Use because of---

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• THE MORALISTIC ERA
• THE FREUDAN ERA
• THE DISEASE ERA

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The synapse and synaptic neurotransmission
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PEARL TIME

• REPEATED STIMULATION OF THE REWARD PATHWAY LEADS
  TO CHANGES IN THE BRAIN.
• THESE CHANGES LEAD TO THE ADDICTION SWITCH BEING
  TURNED ON
• THIS LEADS TO LOSS OF CONTROL, IRRESPECTIVE OF
  THE WILL OF THE INDIVIDUAL

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Brain Reward Pathways

• The VTAnucleus accumbens pathway is activated by
  all drugs of dependence, including alcohol
• This pathway is important not only in drug
  dependence, but also in essential physiological
  behaviors such as eating, drinking, sleeping, and
  sex

Source Messing RO. In Harrisons Principles of
Internal Medicine. 15th ed. 20012557-2561.
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Effects of Acute Alcohol on Reward Circuits
Dopamine and Opioid Systems

• Indirectly increase dopamine levels in the
  mesocorticolimbic system
• Associated with positively reinforcing/ rewarding
  effects of alcohol
• Indirect interaction with opioid receptors
  results in activation of opioid system
• Associated with reinforcing effectsvia
  µ-receptors

Sources Koob GF, et al. Neuron.
199821467-476. Messing RO. In Harrisions
Principles of Internal Medicine. 15th ed.
20012557-2561.
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Relapse and Conditioning

• Repeated alcohol use has caused conditioning to
  occur in related circuits
• Now cues associated with alcohol use can
  activate the reward and withdrawal circuit
• This can evoke anticipation of alcohol or
  feelings similar to withdrawal that can
  precipitate relapse in an abstinent patient

Source Messing RO. In Harrisons Principles of
Internal Medicine. 15th ed. 20012557-2561.
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DILEMMAS

• You give a drug of addiction to anyone and their
  Dopamine levels increase.
• Frequently the increase in Dopamine associated
  with drugs of abuse is less in the addict than in
  the non-addict.
• Some addictive drugs effect the transporter and
  others the receptor.

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SALIENT STIMULI

• Something that is important, pleasurable or
  worth paying attention to.
• Dopamine signals salience.
• Addicts have a decrease in D2 receptors
  therefore decreased sensitivity to salient
  stimuli
• Drugs of abuse block the transporter resulting in
  a long, lasting reward.
• For the addict natural stimuli are not salient
  but the drug of abuse is.

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SALIENT STIMULI

• Drug naive individuals have a wide range of D2
  receptors.
• Give an addictive drug to those with high levels
  of D2 receptors they find it aversive.
• Give an addictive drug to those with low levels
  of D2 receptors they find it rewarding.

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SALIENT STIMULI

• Decreased levels of D2 receptors closely
  correlated to decreased metabolism in orbital
  frontal cortex and cingulate gyrus in response to
  cocaine, alcohol, methamphetamine, and marijuana.

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• THE MORALISTIC ERA
• THE FREUDAN ERA
• THE DISEASE ERA
• THE MANAGED CARE ERA

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• REACTION TO RISING MENTAL HEALTH CARE COSTS
• REACTION TO OVERDIAGNOSIS
• REACTION TO COOKIE CUTTER TREATMENT
• IN SOME CASES MANAGED CARE BECAME MANAGED
  DOLLAR
• FEDERAL LEGISLATION (ERISA OTHERS) LED TO ABUSE
  OF TREATMENT SYSTEM

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• THE MORALISTIC ERA
• THE FREUDAN ERA
• THE DISEASE ERA
• THE MANAGED CARE ERA
• ?????????

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CURRENT STATUS

• MAJOR ADVANCES IN THE NEUROCHEMISTRY AND GENETICS
  OF ADDICTION CONTINUE
• NEW MEDICATIONS ARRIVING ON THE SCENE THAT HELP
  WITH DETOX ISSUES AND CRAVING

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CURRENT STATUS

• NO HOSPITAL BASED INPATIENT PROGRAMS LEFT.
• NO DETOX BEDS LEFT
• PROGRAMS THAT REMAIN ARE LARGELY DEPENDENT ON
  STATE FUNDING
• INSURANCE PARITY ISSUES

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CURRENT STATUS

• LARGEST PROVIDER OF CD TREATMENT IS THE
  CORRECTIONS INDUSTRY
• From 1980-1996 the number of people in prison
  tripled due to criminal activity spawned by drug
  and alcohol abuse
• If this rate continues 1/20 Americans born in
  1997 will spend time in prison
• 1/11 men
• 1/4 African American men

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CURRENT STATUS

• LARGEST PROVIDER OF CD TREATMENT IS THE
  CORRECTIONS INDUSTRY
• Females make up about 10 but rate is rising
  twice the rate for men
• 80 inmates are substance abusers
• 30 increase in spending to build and operate
  prisons
• 3 increase in Medicaid spending

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EVIDENCE-BASED PRACTICE

• EBP aims to disseminate promote
  research-supported treatments to increase the
  efficacy of services to individual patients and
  thereby enhance public health.

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• SAMHSA has a national registry of Evidence-Based
  Programs Practices at www.nrepp.samhsa.gov
• Being included in the registry is NOT AN
  ENDORSEMENT BY SAMHSA of the scientific validity
  or practicality of the interventions listed.
• There are hundreds of programs and practices
  listed.

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• Very difficult to do unbiased, scientific studies
  of various treatment modalities.
• Not as difficult to do studies of pharmacological
  interventions.
• One method of assessing ESP is to seek the
  opinion of a diverse, large number of experts
  regarding substance abuse treatments that can be
  accredited and those that can be discredited.

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WHAT WORKS

• 12 Step facilitation of alcohol and drug
  dependence.
• Minnesota model for alcohol dependence.
• Milieu residential treatment.
• Group process psychotherapy for alcohol
  dependence
• Pharmacological interventions

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WHAT WORKS

• Many names for various counseling techniques
• Reality Therapy
• Rational Emotive Therapy
• Cognitive Behavioral Therapy
• Dialectical Behavior Therapy
• Motivational Interviewing

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ADDICTION MEDICATIONS

• Antabuse for alcoholism
• Naltrexone for alcoholism and opiate dependency
• Acamprosate for alcoholism
• Methadone for opiate dependency
• Suboxone for opiate dependency

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ADDICTION TREATMENT MEDICATIONS

• Disulfiram Antabuse

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ADDICTION TREATMENT MEDICATIONS

• Disulfiram Antabuse
• Naltrexone Revia

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NALTREXONE

• Well absorbed by mouth
• Long duration of action
• Useful for narcotic relapse---esp. in medical
  professionals
• Some hepatic toxicity
• Short term trials indicate helpful with
  alcoholism

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ADDICTION TREATMENT MEDICATIONS

• Disulfiram Antabuse
• Naltrexone Revia
• Acamprosate Campral

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Alcohol Neuropharmacology and Reward Pathways
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Features of Alcohol Dependence
Normal
Tolerance
Acute Alcohol Intake
Adaptation
Alcohol
Alcohol
Excitation(Glutamate)
Inhibition(GABA)
Acute Withdrawal
Post-Acute Withdrawal
Adaptation
Adaptation
Extended symptoms (eg, sleep/mood disturbances)
Source De Witte. Addict Behav.
200429(7)1325-1339.
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Neuroadaptation Potential for Relapse
Normal
Tolerance
Acute Alcohol Intake
Adaptation
Alcohol
Alcohol
Excitation(Glutamate)
Inhibition(GABA)
Acute Withdrawal
Post-Acute Withdrawal
Other mechanisms are also implicated in
relapse (eg, Conditioned Cues)
Adaptation
Adaptation
Potential for Relapse
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Neuroadaptation Potential for Relapse
Normal
Tolerance
Acute Alcohol Intake
Adaptation
Alcohol
Alcohol
Excitation(Glutamate)
Inhibition(GABA)
Post-Acute Withdrawal and Cue-Induced Responses
Acute Withdrawal
C
Adaptation
Campral may balance glutamate overactivity thus
reducing the potential for relapse
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ADDICTION TREATMENT MEDICATIONS

• Disulfiram Antabuse
• Naltrexone Revia
• Acamprosate Campral
• Methadone Dolophine

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METHADONE

• A tablet or liquid for patients dependent on
  opioids
• An stong long acting opioid agonist
• Approved by FDA for specially licensed clinic
  management of opioid dependence
• High affinity for the opioid receptor
• Blocks the effects of opioid agonists
• Is not easily displaced by other opioids

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METHADONE

• Due to long half-life less euphoric rush than
  most opiates
• Strong physical dependence
• Reduced cravings
• Danger of overdose especially when combined with
  other downers

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METHADONE

• SLOW DISSOCIATION from the opioid receptor
  results in
• A prolonged therapeutic effect
• Once-daily dosing
• HOWEVER a severe clinical withdrawal profile

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ADDICTION TREATMENT MEDICATIONS

• Disulfiram Antabuse
• Naltrexone Revia
• Acamprosate Campral
• Methadone Dolophine
• Buprenorphine Suboxone

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SUBOXONE

• A sublingual tablet or film for patients
  dependent on opioids
• Primary active ingredient is buprenorphine, a
  partial opioid receptor agonist
• Other ingredient is naloxone a potent opiate
  antagonist
• Approved by FDA for office-based medical
  management of opioid dependence

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BUPRENORPHINE

• HIGH AFFINITY for the opioid receptor
• Blocks the effects of opioid agonists
• Is not easily displaced by other opioids

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BUPRENORPHINE

• LOW INTRINSIC ACTIVITY
• Less euphoria than a full agonist thus
• Less potential for abuse, but significant
  positive effects to aid in compliance
• Less physical dependence
• Reduced cravings
• Less danger of overdose due to it ceiling effect
  on respiratory depression

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BUPRENORPHINE

• SLOW DISSOCIATION from the opioid receptor
  results in
• A prolonged therapeutic effect with lower dosing
• Once-daily dosing
• A milder withdrawal profile