1. Prescription Drug Abuse Epidemic: A Nation in Crisis Arkansas Drug Court Conference April 9, 2015 Michael Mancino, M.D. Program Director UAMS Center for Addiction Services and Treatment

2. This Presentation Reviews Part I: The problem Part II: Potential solutions

3. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

4. Part II: Potential Solutions Reasons for prescription drug misuse Factors in prescription drug misuse Intervention strategies Treatment

5. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

6. Definitions Misuse Non-medical use Abuse Dependence/Addiction

7. Prescriptions Misuse Incorrect use –By patient Mismanaged –By physicians D ated D uped D isabled D ishonest Non-medical Illegal use Not prescribed Took for euphoria Most commonly used In US, age 12 +: Past month 2% Lifetime: 14% © AMSP

8. Abuse Not if dependent 1 in 12 months: – –Failure to fulfill role – –Use in hazardous situations – –Legal problems – –Use despite problems © AMSP

9. Dependence 3 + in same 12 months – –Tolerance – –Withdrawal – –Larger and Longer use than intended – –Can’t quit – –Much time obtaining, using, or recovering – –  activities – –Continued use despite problems

10. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

11. Non-medical use Most common agents - Stimulants - Sedative/hypnotics - Pain relievers

12. Non-medical use 2013 National Survey on Drug Use and Health (NSDUH) – –7 % youth 12-17 lifetime non-medical use 2013 NSDUH – –20 % young adults 18-25 lifetime non- medical use

13. Non-medical Stimulant Use 2014 Monitoring the Future Study (MTF) – –9 % past year non-medical use of Ritalin/Adderall in 12 graders Diversion – –25 % students giving/selling Ritalin – –27 % gave away or “loaned” medication

14. Emergency Department Visits 2009 Drug Abuse Warning Network (DAWN) 4.6 million drug-related ED visits 45 % were drug misuse – –27 % non-medical use of pharmaceuticals – – 50 % of these were opioid analgesics

15. Prescription Opioids

17. Epidemiology Heroin Use National Household Survey on Drug Use and Health (NSDUH 2013) 681,000 Americans used heroin at least once 169,000 new users Prescription Opioids (NSDUH 2013) 4.5 million used opioid analgesics non-medically $72 billion cost in 2007 In 2009 Drug OD deaths > MVA deaths

18. Arkansas NSDUH Data 2012-2013 Data for ages 12 and older Past year non-medical use: 131,000 or 7 % of the Arkansas population 60,000 (2.5%) of Arkansans reported needing but NOT receiving treatment for illicit drug use Admissions to treatment for opiates in Arkansas (TEDS) 200620072010 Heroin404053 Other opiates77811861707

19. Opioid dependence: Treatment Gaps Patients with dependence (NSDUH-2013) Pain relievers: 1.9 million Heroin: 517,000 Less than half received any treatment Detoxification: limited effectiveness Access to treatment restricted

20. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

21. Case Study   55 Y/O male   Physician   High intelligence   Amphetamine dependent   Multiple prior treatments   Negative consequences: unemployed   Repeated relapses   Wants to quit 21 © AMSP

22. How Are Decisions Made? 22 Mental process  Neurocognitive Involves 3 stages Interconnected Experience-driven © AMSP

23. 23 Stage 1: Stimulus Assessment  Preference  Valence  Salience  Context © AMSP

24. 24 Stage 1: Assessment Stage 2: Execution  Action selection  Action performance © AMSP

25. 25 Stage 3: EFFECT!!  Evaluation/feedback: pros and cons of choice © AMSP

26. 26 Stage 1: Assessment Stage 2: Execution Stage 3: Effect Stage 3: Learning © AMSP

27. Stages in the Case 27  Stage 2 (Execution) Became obsessed Unable to fight impulse  Stage 3 (Effect & Learning) Use  pleasure, relief  drug use reinforced  Stage 1 (Assessment) Saw friend use Frustrated/stressed © AMSP

28. AccVTA FCX AMYG VP ABN Raphé LC GLU GABA ENK OPIOID GABA DYN 5HT NE HIPP PAG RETIC To dorsal horn END DA GLU Opiates ICSS Amphetamine Cocaine Opiates Cannabinoids Phencyclidine Ketamine Opiates Ethanol Barbiturates Benzodiazepines Nicotine Cannabinoids OPIOID HYPOTHAL LAT-TEG BNST NE CRF OFT

29. Dopamine   Salience   Cost benefit analysis 29  Action  Inhibitory control  ‘High’  Learning © AMSP Stage 1: Assessment Stage 2: Execution Stage 3: Effect & Learning 

30. 30 Glutamate   Learning  Stimulus  Preference © AMSP Stage 1: Assessment Stage 2: Execution Stage 3: Learning

31. 31 Noradrenaline   Stress response Sympathetic NS CRF release  Focus on task  Exploration © AMSP Stage 1:Assessment Stage 2: Execution Stage 3: Learning

32. 32 Decision Making In SUDs   Failure at any of 3 stages   Biological root   Possible pre-morbid deficits   Worsened by drug use  DA release to reward  DA receptor density  NA and CRF to stress © AMSP

33. 33 Assessment Deficits   Response to cue   Preference,short-term reward/”high”   Stress,  cue salience © AMSP

34. Execution Deficits Habitual actions favored Can’t see other options  Inhibitory control Can’t hold back 34 © AMSP

35. Execution Deficits Habitual actions favored Can’t see other options  Inhibitory control Can’t hold back 35 © AMSP

36. Effect/Learning Deficits   Imbalanced reward encoding First drug use,  reward Once dependent o o  Drug reward o o Further drug consumption    Learning from negative 36 © AMSP

37. Case Study   Assessment:  preference for drug   Execution:  inhibitory control   Effect:  /  response to drug   Learning:  response neg consequence 37 © AMSP

38. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

39. Two States of Concern Intoxication Withdrawal

40. Opioid Intoxication Miosis (Except Demerol-Ciliary body paralysis-mydriasis) Nodding Hypotension Depressed Respiration Bradycardia Euphoria Floating Feeling

41. Opiate Withdrawal Early Lacrimation Yawning Rhinorrhea Sweating Middle Restless Sleep Dilated Pupils Anorexia Piloerection (term cold turkey) Irritability Tremor

42. Late Opiate Withdrawal ↑ all previous S/S Tachycardia Hypertension Nausea/vomiting Diarrhea Abdominal cramps Abdominal cramps Labile mood Labile mood Depression Depression Muscle spasm Muscle spasm Weakness Weakness Bone pain Bone pain

43. Depressant Intoxication Disinhibition of normal social functioning (excessive talking, showing off) Loss of memory Confusion Disorientation Movement not coordinated Progressive lethargy Coma Ultimately shutdown respiratory centers (death)

44. Depressant Withdrawal Symptoms – –Sweating – –Anxiety – –Tremor agitation – –Nausea – –Headache – –Increased Vital Signs –Hallucinations –Seizures –Delirium (Delirium Tremens, DT’s) –Unstable Vital Signs –Death

45. Stimulant Intoxication Mild intoxication – heightened alertness, elevated mood, euphoria, grandiosity, talkativeness, increased energy, dilated pupils, tremor, increased reflexes, bruxism, increased blood pressure and heart rate (can look like mania), emotional and behavioral lability Moderate intoxication – may involve agitation, hallucinations (AH/VH/TH)

46. Stimulant Withdrawal Symptoms - Dysphoria - Irritability - Fatigue - Insomnia (may mimic depression)

47. Part I: The Problem Definitions Epidemiology What is going on   In the brain   In the body

48. Questions?

49. Prescription Drug Abuse Epidemic: A Nation in Crisis Arkansas Drug Court Conference April 9, 2015 Michael Mancino, M.D. Program Director UAMS Center for Addiction Services and Treatment

50. This Presentation Reviews Part I: The problem Part II: Potential solutions

51. Part II: Potential Solutions Reasons for prescription drug misuse Factors in prescription drug misuse Intervention strategies Treatment

52. Non-Medical Stimulant Use

53. Non-medical Use Rx Opioids

54. High School Seniors Rx Opioids

55. Pain Relief Non-medical Pain Relief

56. Angst? Generational Angst?

57. Part II: Potential Solutions Reasons for prescription drug misuse Factors in prescription drug misuse Intervention strategies Treatment

58. Factors Contributing Factors

59. Protective Factors Parental discussion about risks Gatekeeper access to Rx drugs School based programs – –Science curriculum – –Media awareness training Pharmaceutical approaches

60. Awareness of Teens “Lingo” Pharming Pilz Pharm parties Trail mix or M & M’s Chill pills Big boy

61. Part II: Potential Solutions Reasons for prescription drug misuse Factors in prescription drug misuse Intervention strategies Treatment

62. Prevention  Exposure  Target high-risk Adolescents Adolescents Genetically vulnerable Genetically vulnerable Cognitive probs (schizophrenia, brain injury) Cognitive probs (schizophrenia, brain injury)  Stress reactive (depressed/anxious)  Stress reactive (depressed/anxious) 62 © AMSP

63. Intervention School Nurses School Nurses Computerized, involve parents Computerized, involve parents Cognitive Behavioral Therapy Cognitive Behavioral Therapy Motivational Interviewing Motivational Interviewing Medication Assisted Treatment Medication Assisted Treatment

64. Part II: Potential Solutions Reasons for prescription drug misuse Reasons for prescription drug misuse Factors in prescription drug misuse Factors in prescription drug misuse Intervention strategies Intervention strategies Treatment Treatment

65. MEDICATION/PSYCHOSOCIAL

67. Medications  Drug cue effect 67  Naltrexone (AUDs), opioid blocker  DA release  Craving  Relapse © AMSP

68. Medications  Negative emotional states   drug craving 68  Methadone/Buprenorphine (opioid use disorder)  Withdrawal/craving  Brain stress response/  anxiety  Treat co-occurring disorders © AMSP

69. 69 Medications  Drug reward  Under development  Cocaine & nicotine vaccines  Abs block drug entry into brain © AMSP

70. Impact of Maintenance Treatment Reduction death rates (Grondblah, ‘90) Reduction IVDU (Ball & Ross, ‘91) Reduction crime days (Ball & Ross) Reduction rate of HIV seroconversion (Bourne, ‘88; Novick ‘90,; Metzger ‘93) Reduction relapse to IVDU (Ball & Ross) Improved employment, health, & social function

71. Psychotherapies   Contingency Management Therapy Reward changes behaviors Learn abstinence  earn $$$   Relapse Prevention Therapy Identify triggers Learn avoidance 71 © AMSP

72. Part II: Potential Solutions Reasons for prescription drug misuse Factors in prescription drug misuse Intervention strategies Treatment

73. Questions?