1. Methamphetamine and the Brain: What do we know? Beth Rutkowski, M.P.H. Pacific Southwest Addiction Technology Transfer Center UCLA Integrated Substance Abuse Programs finnerty@ucla.edu UCEDD ID Grand Rounds, March 22, 2006 11:00 a.m. – 12:00 p.m.

2. Forms of Methamphetamine Methamphetamine Powder Users’ Description: Beige/yellowy/off-white powder Base / Paste Methamphetamine Users’ Description: ‘Oily’, ‘gunky’, ‘gluggy’ gel, moist, waxy Crystalline Methamphetamine Users’ Description: White/clear crystals/rocks; ‘crushed glass’ / ‘rock salt’

3. Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1992 (per 100,000 aged 12 and over) 35 - 58 12 - 35 < 12 No data > 58 SOURCE: 2002 SAMHSA Treatment Episode Data Set (TEDS).

4. < 12 35 - 58 12 - 35 < 12 No data > 58 Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1997 (per 100,000 aged 12 and over) SOURCE: 1997 SAMHSA Treatment Episode Data Set (TEDS).

5. < 12 12 - 35 58-99 35 -58 150-199 200 or more 100-149 Primary Amphetamine/Methamphetamine TEDS Admission Rates: 2002 (per 100,000 aged 12 and over) SOURCE: 2002 SAMHSA Treatment Episode Data Set (TEDS).

6. Primary Amphetamine/Methamphetamine TEDS Admission Rates: 2003 (per 100,000 aged 12 and over) < 12 12 - 35 58-99 35 -58 150-199 200 or more 100-149 SOURCE: 2003 SAMHSA Treatment Episode Data Set (TEDS).

7. A Major Reason People Take a Drug is they Like What It Does to Their Brains A Major Reason People Take a Drug is they Like What It Does to Their Brains

12. synapse dopamine reservoir

15. Methamphetamine

16. Initially, A Person Takes A Drug Hoping to Change their Mood, Perception, or Emotional State Initially, A Person Takes A Drug Hoping to Change their Mood, Perception, or Emotional State Translation--- …Hoping to Change their Brain

17. 0 0 50 100 150 200 0 0 60 120 180 Time (min) % of Basal DA Output NAc shell Empty Box Feeding Source: Di Chiara et al. FOOD Natural Rewards Elevate Dopamine Levels

18. Source: Shoblock and Sullivan; Di Chiara and Imperato Effects of Drugs on Dopamine Release 0 0 100 200 300 400 Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 100 150 200 250 01234hr Time After Ethanol % of Basal Release 0.25 0.5 1 2.5 Accumbens 0 Dose (g/kg ip) ETHANOL 0 0 100 150 200 250 0 0 1 1 2 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Time After Methamphetamine % Basal Release METHAMPHETAMINE 0123hr 1500 1000 500 0 Accumbens

19. After A Person Uses Drugs For A While, Why Can’t They Just Stop? After A Person Uses Drugs For A While, Why Can’t They Just Stop? But Then…

20. Their Brains have been Re-Wired by Drug Use Their Brains have been Re-Wired by Drug Use Because…

21. Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways

22. PET Scan of Long-Term Impact of Methamphetamine on the Brain

23. Source: McCann U.D.. et al.,Journal of Neuroscience, 18, pp. 8417-8422, October 15, 1998. Decreased dopamine transporter binding in METH users resembles that in Parkinson ’ s Disease patients

24. Control > MA 4 3 2 0 1

25. MA > Control 5 4 2 0 1 3

26. Dopamine Transporters in Methamphetamine Abusers p < 0.0002 Normal Control Methamphetamine Abuser 78910111213 1.0 1.2 1.4 1.6 1.8 2.0 Time Gait(seconds) Dopamine Transporter (Bmax/Kd) 46810121416 1 1.2 1.4 1.6 1.8 2 Delayed Recall (words remembered) Dopamine Transporter Bmax/Kd Motor Activity Memory

27. Cognitive Impairment in Individuals Currently Using Methamphetamine Sara Simon, Ph.D. VA MDRU Matrix Institute on Addictions LAARC

28. Differences between Stimulant and Comparison Groups on tests requiring perceptual speed

29. Memory Difference between Stimulant and Comparison Groups

30. Longitudinal Memory Performance test number correct

31. How much does the brain heal?

32. PET Scan of Long-Term Meth Brain Damage

33. Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence Normal Control METH Abuser (1 month detox) METH Abuser (24 months detox) 0 3 ml/gm Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

34. Control Subject (30 y/o, Female) METH Abuser (27 y/o, Female) 3 months detox METH Abuser (27 y/o, Female) 13 months detox µmol/100g/min 70 0 Partial Recovery of Brain Metabolism in Methamphetamine (METH) Abuser after Protracted Abstinence Source: Wang, G-J et al., Am J Psychiatry 161:2, February 2004.

35. Effects of Methamphetamine and Treatment Implications

36. Methamphetamine Acute Physical Effects Increases Decreases Heart rate Appetite Blood pressure Sleep Pupil size Reaction time Respiration Sensory acuity Energy

37. Methamphetamine Acute Psychological Effects Increases –Confidence –Alertness –Mood –Sex drive –Energy –Talkativeness Decreases –Boredom –Loneliness –Timidity

38. Methamphetamine Chronic Physical Effects -Tremor - Sweating - Weakness - Burned lips; sore nose - Dry mouth - Oily skin/complexion - Weight loss - Headaches - Cough - Diarrhea - Sinus infection - Anorexia

39. Methamphetamine Chronic Psychological Effects - Confusion - Irritability - Concentration - Paranoia - Hallucinations - Panic reactions - Fatigue - Depression - Memory loss - Anger - Insomnia - Psychosis

40. Other problems Eye ulcers Over-heating Rhabdomyolysis Obstetric complications Anorexia / weight loss

41. Severe weight loss/anorexia

42. Faces of Methamphetamine Speed Bumps Images courtesy Multnomah County Sheriff’s Office

43. Source: The New York Times, June 11, 2005. “METH Mouth” METH Use Leads to Severe Tooth Decay Source: Richards, JR and Brofeldt, BT, J Periodontology, August 2000. Source: Richards, JR and Brofeldt, BT, J Periodontology, August 2000.

45. Methamphetamine Psychiatric Consequences Paranoid reactions Permanent memory loss Depressive reactions Hallucinations Psychotic reactions Panic disorders Rapid addiction

46. Outpatient Treatment for Methamphetamine Abuse

47. www.drugabuse.gov

48. Treatment: Medical & Behavioral Drugs Sedatives Stimulants Opioids Alcohol Medical Treatment Yes No Yes Behavioral Treatment Yes

49. MATRIX MODEL TREATMENT Primary Manifestation of Withdrawal Stage BehavioralCognitive RelationshipEmotional Behavioral Inconsistency Confusion Inability to Concentrate Depression/Anxiety- Self-Doubt Mutual Hostility- Fear

50. STAGES OF RECOVERY - STIMULANTS OVERVIEW Withdrawal Honeymoon The Wall Adjustment Resolution DAY 0 DAY 15 DAY 45 DAY 120 DAY 180

51. Stages of Recovery - Stimulants WITHDRAWAL STAGE DAY 0 DAY 15 Medical Problems Alcohol Withdrawal Depression Difficulty Concentrating Severe Cravings Contact with Stimuli Excessive Sleep PROBLEMS ENCOUNTERED

52. Matrix Model Treatment Key Concept: Structure Self-designed structure (scheduling) Eliminate avoidable triggers Makes concrete the concept of “One day at a time” Reduces anxiety Counters the addict lifestyle Provides basic foundation for ongoing recovery

53. MATRIX MODEL TREATMENT STRUCTURE Treatment Program Activities Recreational/Leisure Activities 12-Step Meetings School SportsBeing with Drug-free Friends Time SchedulingExercise WorkFamily-related Events Church/SynagogueIsland Building

54. Stages of Recovery - Stimulants HONEYMOON STAGE DAY 15 DAY 45 Over-involvement With Work Overconfidence Inability to Initiate Change Inability to Prioritize Alcohol Use Episodic Cravings Treatment Termination PROBLEMS ENCOUNTERED

55. Return to Old Behaviors Anhedonia Anger Depression Emotional Swings Unclear Thinking Isolation Family Problems Cravings Return Irritability Abstinence Violation

56. Relationship Problems Boredom Lack of Goals Guilt and Shame Career Dissatisfaction Underlying Psychopathology May Surface or Resurface

57. Achieving a Balanced Life Work Recovery Activities Sleep Leisure Relationships

58. Limitations on Current Treatments Training and development of knowledgeable clinical personnel are essential elements to successfully address the challenges of treating MA users. Training alone is insufficient if the funding necessary to deliver these treatment recommendations is not available. Treatment funding policies that promote short duration or non-intensive outpatient services are inappropriate for providing adequate funding for MA users.

59. Successful Outpatient Treatment Predictors Durations over 90 days (with continuing care for another 9 months). Techniques and clinic practices that improve treatment retention are critical. Treatment should include 3-5 clinic visits per week for at least 90 days. Employ evidence based practice (e.g., CBT, CM, Community Reinforcement Approach, Motivational Interviewing, Matrix Model). Family involvement and 12-step program appear to improve outcome. Urine testing (at least weekly is mandatory)

60. Optimal candidates for Outpatient Treatment Include: Those who do not inject MA. Those without chronic mental illness and those without significant psychiatric symptoms at admission. Those who are using MA less than daily at admission. Those under legal supervision (especially drug court). Older individuals (over 21)Those who are not disabled. Those who have a stable living situation (without active drug users).

61. Special Treatment Consideration Should be Made for the Following Groups of Individuals: MA users who take MA daily or in very high doses. Homeless, chronically mentally ill and/or individuals with high levels of psychiatric symptoms at admission. Individuals under the age of 21. Gay men (at very high risk for HIV and hepatitis).

62. For more information, please contact Beth Rutkowski at 310-445-0874 x376 or finnerty@ucla.edu www.uclaisap.org or www.psattc.org