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Substance-Related Disorders

Substance-Related Disorders. Brian Ladds, M.D. Outline. A neuro-biological perspective Definitions Specific substances. Substance Abuse. Why do people use psychoactive substances? Why do they persist?. Pleasure & Reward Circuit. Stimulation of this pathway leads to feelings of pleasure

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Substance-Related Disorders

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  1. Substance-Related Disorders Brian Ladds, M.D.

  2. Outline • A neuro-biological perspective • Definitions • Specific substances

  3. Substance Abuse Why do people use psychoactive substances? Why do they persist?

  4. Pleasure & Reward Circuit • Stimulation of this pathway leads to feelings of pleasure • Dopamineproduces these feelings

  5. Meso-Accumbens Pathway • From mid-brain to limbic system and back: • Meso-Accumbens pathway • From the VTA to the Nucleus Accumbens • From Nucleus Accumbens back to VTA

  6. Inputs to the Pleasure/Reward Circuit • Inputs to VTA and/or Nucleus Accumbens: • from other parts of brain • using a variety of neurotransmitters • Glutamate • GABA • Opioid peptide neurotransmitter • Other inputs

  7. Hijacking the “Pleasure & Reward Circuit” • This circuit is hijacked by all substances of abuse • All are extremely potent at stimulating this circuit • Pleasure from ordinary activities come to have diminished power in this circuit

  8. Actions of Substances of Abuse • All substances of abuse increase dopamine effects in this circuit • They do so by acting at: • the VTA, and/or: • the Nucleus Accumbens • They act to: • increase dopamine release, and/or • block re-uptake

  9. Neuro-adaptations • Upon repeated use, the brain tries to counter-act the effects of these substances • Such neuro-adaptations involve changes in structure and function

  10. Neuro-adaptations • Neuro-adaptations, esp. in the brain stem, may lead to: • Diminished effects of a given substance (‘tolerance’) • Effects upon its discontinuation (‘withdrawal’)

  11. Relapse • What triggers a return to use a drug after prolonged abstinence?

  12. Definitions • Additional definitions and concepts • DSM-IV classification and criteria

  13. Behaviors • Tolerance • Withdrawal • Sensitization • Craving • Dependence • Abuse

  14. Tolerance • Tolerance develops at different rates for different actions of a drug • Euphoria caused by cocaine diminishes faster than its cardiostimulant effects

  15. Withdrawal • The signs and symptoms that occur when a drug is stopped or dose lowered • Both physiological and psychological processes contribute

  16. Withdrawal • Can cause secondary problems • Depression and anxiety from cocaine • Excito-toxic brain damage from alcohol

  17. Sensitization • An increase in an effect of a drug upon its repeated administration • Tends to be seen with the stimulating actions of a drug

  18. Sensitization: Examples • Cocaine use • Psychotimimetic effects of cocaine • Alcohol withdrawal • Excitatory changes in withdrawal • alcohol withdrawal progressively worsens

  19. DSM-IV Definitions • Substance-Related Disorders • Substance Use Disorders • Substance Dependence • Substance Abuse • Substance-Induced Disorders

  20. Substance-Induced Disorders • Intoxication • Withdrawal • Other • Delirium • Persisting Dementia • Persisting Amnestic Disorder • Psychotic Disorder • Mood Disorder • Anxiety Disorder • Sexual Dysfunction • Sleep Disorder

  21. Criteria for Substance Dependence • A maladaptive pattern of substance use, • leading to clinically significant impairment or distress, • as manifested by at least 3 of the following 7 criteria, • occurring at any time in the same 12-month period

  22. Criteria for Substance Dependence 1. Tolerance 2. Withdrawal 3. The substance is often taken in larger amounts or over longer periods than was intended

  23. Criteria for Substance Dependence 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects

  24. Criteria for Substance Dependence 6. Important social, occupational or recreational activities are given up or reduced because of substance use 7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance

  25. Dependence: Sub-types • Specify subtype: • ‘With physiological dependence’ • Evidence of tolerance or withdrawal • ‘Without physiological dependence’ • No evidence of tolerance or withdrawal

  26. Criteria for Substance Abuse • A maladaptive pattern of substance use, • leading to clinically significant impairment or distress, • as manifested by at least 1 of the following criteria, • occurring within a 12-month period

  27. Criteria for Substance Abuse 1. Recurrent substance use resulting in failure to fulfill major role obligations at work, school, or home 2. Recurrent substance use in situations in which it is physically hazardous 3. Recurrent substance-related legal problems

  28. Criteria for Substance Abuse 4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance B. The symptoms have never met the criteria for Substance Dependence for this class of substance.

  29. Specific Substances

  30. Prevalence

  31. Pharmacokinetic Factors • Important in determining the misuse potential of a drug • Oral vs. nasal vs. smoked vs. IV • Cocoa leaves vs. powder cocaine vs. lipophilic free-base cocaine (“crack”)

  32. Alcohol-related disorders • Alcohol abuse is several times more common in men • Significant increased risk for accidents, suicide, and violence

  33. Prevalence • Lifetime prevalence of alcohol abuse or dependence is approximately 8%

  34. Etiology • Genetics • 60% monozygotic twins • 25% of children of alcoholic parent • risk increases with: • number of alcoholic relatives, • severity of their illness, and • closeness of genetic relationship

  35. Etiology • Psychological Theories • Socio-cultural Theories

  36. 12 oz beer 4 oz glass wine 1.5 oz liquor (80 proof) 12 grams Ethyl Alcohol

  37. 0.08 Legal intoxication 0.40 Lethal dose, 50% of population (LD50) Blood Alcohol Level (BAL)

  38. Mechanism of Action of Alcohol • Alters the fluidity and organization of cell membranes throughout the brain • Alters the function of proteins that transverse cell membranes, such as neurotransmitter receptors and ion channels • Binds to GABA-A receptor • Acts like a glutamate (NMDA) receptor antagonist

  39. Alcohol effects on the CNS • Blackout • Peripheral Neuropathy • Cerebellar Degeneration • Sleep impairment • Sexual dysfunction • Mood, Anxiety & Psychotic Disorders

  40. Alcohol effects on the CNS Wernicke-Korsakoff’s syndrome • Severe deficiency of thiamine • Ataxia • Amnesia • 6th Nerve palsy (opthalmoplegia)

  41. Alcohol Effects on the Body • Vitamin malabsorption • Severe inflammation: esophagus & stomach • Pancreatitis • Bone marrow suppression • Cancer: esophagus, stomach, head, neck • Hypertension and alcoholic cardiomyopathy • Fatty liver, alcoholic hepatitis, cirrhosis

  42. Alcohol Intoxication • Clinically significant maladaptive behavioral or psychological changes • One (or more) of the following signs: • slurred speech • incoordination • unsteady gait • nystagmus • impairment in attention or memory • stupor or coma

  43. At least 2 of these, within a few days of cessation of (or reduction in) use: Autonomic hyperactivity (Early) Hand tremor (Early) Insomnia (Early) Nausea and vomiting (Early) Psychomotor agitation (Early) (Early) = within 6-8 hours of last drink Alcohol Withdrawal

  44. Alcohol Withdrawal, cont.’ • Hallucinations • transient visual, tactile, or auditory • Grand Mal Seizures • (Later) = 24-72 hours • Delirium Tremens • Treatment

  45. Opium: juice of opium poppy, Papaver Somniferum Natural (or synthesized from naturally occurring opiates): morphine, heroin (diacetyl-morphine), codeine (3-methoxy-morphine), hydromorphone (Dilaudid), oxycodone Synthetic: meperidine (Demerol), methadone (Dolophine), pentazocine (Talwin), proproxyphene (Darvon) Opioids

  46. Endogenous opioids: enkephalins, endorphins Mixed agonist/antagonists: buprenorphine (Buprenex) Antagonists: naloxone (Narcan), naltrexone (ReVia) Opioids

  47. Opioids • Prevalence • Less than 1% with current dependence or abuse

  48. Opioids: Mechanism of Action • Binding to Mu opioid receptors influences mood & reinforcing effects • Stimulate the release of dopamine in the Nucleus Accumbens

  49. ‘Positive’ Effects of Opioids • Tranquility • Euphoria • Decreased apprehension

  50. Opioids:Some Possible Symptoms • Apathy and dysphoria • Analgesia • Decrease respiration • Decrease cough reflex • Constipation

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