2. Methamphetamine: Review of The Problem Igor Koutsenok, MD Assistant Professor of Psychiatry University of California San Diego Associate Director, Center for Criminality & Addiction Research, Training & Application www.ccarta.ucsd.edu

3. Powerfully addictive stimulant that dramatically affects the central nervous system Made easily in labs with OTC ingredients What Is Methamphetamine?

4. The active ingredient in making methamphetamine is ephedrine or pseudoephedrine, commonly found in over the counter cold remedies.

5. Methamphetamine

6. Ephedrine and Methamphetamine

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

8. Speed Methamphetamine powder ranging in color from white, yellow, orange, pink, or brown. Color variations are due to differences in chemicals used to produce it and the expertise of the cooker. Other names: shabu, crystal, crystal meth, crank, tina, yaba

9. Ice High purity methamphetamine crystals or coarse powder ranging from translucent to white

10. Methamphetamine Lab Seizures A small percentage of labs are labeled “Super Labs” and are capable of producing over 10 lbs per batch. Super Labs are operated by Mexican National Drug Trafficking Organizations (MNDTO’s), and supply the majority of meth to the market.

11. Chemical Ingredients Trichloroethane (Gun Scrubber) Ether (Engine Starter) Toluene (Brake Cleaner) Methanol (Gasoline Additive) GasolineKerosene

13. Methamphetamines A Brief History 188719191932 Amphetamine developed Methamphetamine developed Amphetamine & methamphetamine used as decongestant

14. Methamphetamines A Brief History WW II Extensive use by: - Fighter pilots - Fighter pilots - German Panzer troops - German Panzer troops - Japanese workers - Japanese workers - Kamikaze - Kamikaze

15. Methamphetamines A Post-War Epidemic FACTORS Large quantities Social disorganization “Work pills” 500,000 addicts JAPAN

16. Methamphetamines Epidemic in Sweden FACTORS Large supply 3% are users Preludin use widespread Mostly oral use SWEDEN

17. Methamphetamines Factors Related to Epidemic Over supply Opportunity to experience Widespread knowledge A reliable market No need for injections (in most cases) Many “speed labs”

18. Worldwide Trends of Methamphetamine Use WHO 2005 data estimates 42 million meth users worldwide; 15M- heroin; 12M- cocaine Areas of very heavy use: Thailand, Philippines, Indonesia, SE Asia, Eastern Europe, Russia, China Areas of increasing use; Northern Mexico, USA, Canada, South Africa, Europe

19. The Eastward Spread of Methamphetamine Epidemic

22. Total Number of Primary Methamphetamine Admissions:1998-2002 SAMHSA, Treatment Episode Data Set: 1992-2002. 50% Increase from 1998-2002

23. Methamphetamine: A Growing Problem in Rural America In 1998, rural areas nationwide reported 949 methamphetamine labs. In 2003, 9,385 were reported. Source: El Paso Intelligence Center (EPIC), U.S. DEA, 2005

27. Methamphetamine/Amphetamine Treatment Admissions, by Route of Administration: 1992-2002

28. A Major Reason People Take Methamphetamines is they Like What It Does to Their Brains A Major Reason People Take Methamphetamines is they Like What It Does to Their Brains

30. Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perseveration Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe

31. Methamphetamine: Neurochemical Mechanisms Methamphetamine enters the brain through dopamine transporters Enters dopamine vesicles Vesicles deplete themselves of dopamine Free-floating DA produces “free radicals” (neurotoxins). The synapse is flooded with dopamine, producing a profound sense of pleasure

32. 0 0 50 100 150 200 0 0 60 120 180 Time (min) % of Basal DA Output Empty Box Feeding Source: Di Chiara et al. FOOD Natural Rewards Elevate Dopamine Levels

33. 0 0 100 200 300 400 500 600 700 800 900 1000 1100 0 0 1 1 2 2 3 3 4 4 5 hr Time After Amphetamine % of Basal Release DA DOPAC HVA Accumbens AMPHETAMINE 0 0 100 20 0 300 400 0 0 1 1 2 2 3 3 4 4 5 hr Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 0 0 100 150 200 250 0 0 1 1 2 2 3 3 4 4 5hr Time After Morphine % of Basal Release Accumbens 0.5 1.0 2.5 10 Dose (mg/kg) MORPHINE 0 0 100 150 200 250 0 0 1 1 2 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Source: Di Chiara and Imperato, 2004 Effects of Drugs on Dopamine Levels

34. Dopamine Reward Pathway Activation without drugs

35. The brains of people addicted to methamphetamine are different than those of non- addicts Methamphetamine Addiction

37. Axon Neurotransmitter Synapse Dendrite Receptors Reuptake МАО Signal storage G-protein

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

43. Comparison Subject METH user Dopamine Transporter Loss After Heavy Methamphetamine Use

44. Partial Recovery of Brain Dopamine Transporters in Methamphetamine Abuser After Protracted Abstinence Normal control Meth abuser Meth abuser (1 month detox)(24 month in recovery Volkow, ND, Journal of Neurscience, 21, 2001

45. Methamphetamine Cognitive Cognitiveand Memory Effects Memory Effects

46. Executive Systems Functioning Deficits on executive tasks associated with: –Poor judgment. –Lack of insight. –Poor strategy formation. –Impulsivity. –Reduced capacity to determine consequences of actions.

47. Reasons for Meth Use Reasons for using meth were wide-ranging: –To get high (56%) –To get more energy (37%) –To cope with mood (34%) –To lose weight/feel more attractive (29%) –To party (28%) –To escape (27%) –To enhance sexual pleasure (18%) Patterson and Semple (2003) Journal of Urban Health, 80: iii77-iii87

48. Meth and Women Typical gender ratio of heroin users in treatment : 3 men to 1 woman Typical gender ratio of cocaine users in treatment : 2 men to 1 woman Typical gender ratio of methamphetamine users in treatment : 1 man to 1 woman * *among large clinical research populations

49. Self-Reported Reasons for Starting Methamphetamine Use

50. Methamphetamine and Sex

51. My sexual drive is increased by the use of … (Rawson et al., 2002)

52. My sexual pleasure is enhanced by the use of … (Rawson et al., 2002)

53. My sexual performance is improved by the use of … (Rawson et al., 2002)

54. Methamphetamine Incarceration

55. Primary Substance Reported by California Inmates (N=22,903) 6 11.5 15 17.4 21.5 28.8 Cartier J, Farabee D, Prendergast M. Journal of Interpersonal Violence. 2006;21:435-445.

56. Those who used MA (81.6%) were significantly more likely than those who did not use MA (53.9%) to have been returned to custody for any reason or to report committing any violent acts in the 30 days prior to follow-up (23.6% vs. 6.8%) MA use is significantly predictive of violent crime and general recidivism Offenders who use MA may differ significantly from their peers who do not use MA and may require more intensive treatment interventions and parole supervision than other types of drug involved offenders Cartier J, Farabee D, Prendergast M. Journal of Interpersonal Violence. 2006;21:435-445.

57. A history of physical or sexual violence (controlling for gender) is significantly related to meth use and a number of negative treatment outcomes. These results suggest the importance of understanding client background factors before they enter treatment. CSAT Methamphetamine Treatment Project 2003

58. Drug Endangered Children in California: Methamphetamine Use and Manufacture

59. Children are not small adults! Different diet Growing & developing rapidly Higher metabolic & respiratory rate Developing nervous system Unusual habits (hand-to-mouth behaviors; close to floor, contact with many surfaces, at risk for all poisonings) Biologic & developmental vulnerability

60. Children who live in and around the area of the meth lab become exposed to the drug and its toxic precursors and byproducts. Children who live in and around the area of the meth lab become exposed to the drug and its toxic precursors and byproducts. Nationally, over 20% of the seized meth labs in 2002 had children present. Nationally, over 20% of the seized meth labs in 2002 had children present. 80-90% of children found in homes where there are meth labs test positive for exposure to meth. Some are as young as 19 months old. 80-90% of children found in homes where there are meth labs test positive for exposure to meth. Some are as young as 19 months old.

61. Children In 2002, a total of 142 children were present at lab seizures in Riverside and San Bernardino Counties. Most children reported as being present during a seizure were school age.

62. Methamphetamine Treatment

63. Treatment Effectiveness? Common rumors re treatment of clients with MA problems: –MA users are untreatable –Negligible recovery rates (5% to less than 1% have been quoted in newspaper articles) –The resulting conclusion is that spending money on treating MA users is futile and wasteful, –No data exists that supports these statistics

64. Limitations on Current Treatments Training of clinical personnel is essential to successfully treat MA users. Training alone is insufficient if the funding necessary to deliver effective treatment is not available. Treatment funding that promote short duration or non-intensive outpatient services are inappropriate for providing adequate care for MA users.

65. MA Treatment Issues Acute MA Overdose Acute MA Psychosis MA “Withdrawal” Initiating MA Abstinence MA Relapse Prevention Protracted Cognitive Impairment and Symptoms of Paranoia

66. MA Acute Withdrawal DepressionParanoiaFatigue Cognitive Impairment AnxietyAgitationAnergiaConfusion Duration: 2 Days - 2 Weeks Duration: 2 Days - 2 Weeks

67. Psychiatric Symptoms Hallucinations are reported by one-third of MA users. Majority of MA users entered treatment in a state of severe depression. Many are suicidal at treatment admission Intense paranoid ideation are very common in MA users.

68. Medications Currently, there are no medications that can quickly and safely reverse life threatening MA overdose. There are no medications that can reliably reduce paranoia and psychotic symptoms, that contribute to episodes of dangerous and violent behavior associated with MA use.

69. Medication Research for Methamphetamine Dependence Negative Results Unclear Imipramine Gabapentin Desipramine Modafinil Tyrosine Topirimate Ondansetron Disulfiram Fluoxetine Lobeline Aripiprazole Aripiprazole Promising Evidence: Bupropion

70. Bupropion: An effective pharmacotherapy? Newton et al. 2005. –Bupropion reduces craving and reinforcing effects of methamphetamines Elkashef (recently completed) –Bupropion reduces methamphetamine use in an outpatient trial, with particularly strong effect with less severe users.

71. Special treatment consideration should be made for the following groups : Individuals under the age of 21 Female MA users (higher rates of depression; very high rates of previous and present sexual and physical abuse; responsibilities for children). Injection MA users (very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis). 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. Gay men (at very high risk for HIV and hepatitis).

72. Treatments for Stimulant-use Disorders with Empirical Support Motivational Enhancement Strategies Cognitive-Behavioral Therapy (CBT) Community Reinforcement Approach Contingency Management 12 Step Groups

73. Treatment of MA-Use Disorders No medications currently are available with evidence of efficacy Two approaches - Contingency Management and Cognitive Behavioral Treatment have data to support efficacy MA users appear to respond to other treatment interventions in rates comparable to other types of drug users. MA users are responsive to treatment MA users are responsive to treatment

74. Contingency Management A technique employing the systematic delivery of positive reinforcement for desired behaviors. In the treatment of methamphetamine dependence, vouchers or prizes can be “earned” for submission of methamphetamine-free urine samples.

75. Cognitive Behavioral Therapy and Contingency Management CM is an effective treatment for reducing stimulant use and is superior during treatment to a CBT approach alone. CM is useful in engaging substance abusers, retaining them in treatment, and helping them achieve abstinence from stimulant use. CBT also reduces drug use from baseline levels and produces comparable outcomes on all measures at follow-up. Rawson, RA et al. Addiction, Jan 2006, Roll, JM et al, Archives of General Psychiatry, (In Press)

76. Summary Methamphetamine is a significant public health problem in the US and in the world It produces significant damage to the body and the brain Recovery from methamphetamine dependence is possible and most brain changes are reversible. There are effective treatments for methamphetamine dependence.

77. If you have more questions… ikoutzenok@ucsd.edu 858/551 2946