1. Methamphetamine: New Knowledge, Neurobiology and Clinical Issues Richard A. Rawson, Ph.D Professor Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles www.uclaisap.org rrawson@mednet.ucla.edu Supported by: National Institute on Drug Abuse (NIDA) Pacific Southwest Technology Transfer Center (SAMHSA) International Network of Treatment and Rehabilitation Resource Centres (UNODC)

2. Methamphetamine Methamphetamine is a powerful central nervous system stimulant that strongly activates multiple systems in the brain. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of methamphetamine are greater.

3. 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’

4. Types of Stimulant Drugs Amphetamine Type Stimulants (ATS) Amphetamine“Speed” Dexamphetamine“Ice” Methylphenidate “Crank” Methamphetamine“Yaba” “Shabu”

5. Methamphetamine vs. Cocaine Cocaine half-life: 1-2 hours Methamphetamine half-life: 8-12 hours Cocaine paranoia: 4 -8 hours following drug cessation Methamphetamine paranoia: 7-14 days Methamphetamine psychosis - May require medication/hospitalization and may not be reversible Neurotoxicity: Appears to be more profound with amphetamine-like substances

6. EPHEDRINE OH CC HHH 3 CH 3 N

7. The Methamphetamine Epidemic: Admissions/100,000: 1992-2003 It keeps going up

8. Figure 2. Methamphetamine/Amphetamine Treatment Admissions, by Route of Administration: 1992-2002 Source: 2002 SAMHSA Treatment Episode Data Set (TEDS).

9. National Longitudinal Study of Adolescent Health (Add Health). In 2001–2002, 2.8% of young adults reported using crystal methamphetamine in the past year. –Blacks: 0.6%Northeast: 1% –Asians: 1.8%Midwest: 2.2% –Hispanics: 1.8%South: 2.8% –Whites: 3.3%West: 5.3% –Native Americans: 12.8%

10. Admissions for AI/AN Participants in LA County

11. Primary Admissions For Female AI/AN Participants in LA County

13. 0 0 100 200 300 400 Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 0 0 100 150 200 250 0 0 1 1 2 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Source: Shoblock and Sullivan; Di Chiara and Imperato Effects of Drugs on Dopamine Release Time After Methamphetamine % Basal Release METHAMPHETAMINE 0123hr 1500 1000 500 0 Accumbens

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

15. 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.

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

17. Control > MA 4 3 2 0 1

18. MA > Control 5 4 2 0 1 3

19. Defining Domains: Executive Systems Functioning a.k.a. frontal lobe functioning. Deficits on executive tasks assoc. w/: –Poor judgment. –Lack of insight. –Poor strategy formation. –Impulsivity. –Reduced capacity to determine consequences of actions.

20. Brain Serotonin Transporter Density and Aggression in Abstinent Methamphetamine Abusers * * Sekine, Y, Ouchi, Y, Takei, N, et al. Brain Serotonin Transporter Density and Aggression in Abstinent Methamphetamine Abusers. Arch Gen Psychiatry. 2006;63:90-100.

21. Methamphetamine Use, Self-Reported Violent Crime, and Recidivism Among Offenders in California Who Abuse Substances * Cartier J, Farabee D, Prendergast M. Methamphetamine Use, Self-Reported Violent Crime, and Recidivism Among Offenders in California Who Abuse Substances. Journal of Interpersonal Violence. 2006;21:435-445.

22. Results 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%, respectively)

23. Implications of Results These findings suggest that 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 offenders who use drugs

24. Neural Activation Patterns of Methamphetamine-Dependent Subjects During Decision Making Predict Relapse * * Paulus M, Tapert S, Schuckit M. Neural Activation Patterns of Methamphetamine-Dependent Subjects During Decision Making Predict Relapse. Arch Gen Psychiatry. 2005;62:761-768.

25. Results Continued –Right insula, right posterior cingulate, and right middle temporal gyrus response best differentiated between relapsing and nonrelapsing participants Cross-validation analysis was able to correctly predict 19 of 22 who did not relapse and 17 of 18 who relapsed –Right middle frontal gyrus, right middle temporal gyrus, and right posterior cingulate cortex activation best predicted time to relapse

26. Implications of Results Neural activation differences are part of a system involved with the processing of decision making. Attenuated activation may represent: Diminished ability to differentiate choices that lead to good vs. poor outcomes fMRI may prove to be a useful clinical tool to assess relapse susceptibility

27. Methamphetamine Abuse, HIV Infection Causes Changes in Brain Structure Jernigan,T, et al American Jnl of Psychiatry Aug 2005 Methamphetamine abuse and HIV infection cause significant alterations in the size of certain brain structures, and in both cases the changes may be associated with impaired cognitive functions, such as difficulties in learning new information, solving problems, maintaining attention and quickly processing information. Co-occurring methamphetamine abuse and HIV infection appears to result in greater impairment than each condition alone

28. Methamphetamine Abuse, HIV Infection Causes Changes in Brain Structure Jernigan,T, et al American Jnl of Psychiatry Aug 2005 Younger methamphetamine abusers showed larger effects in some brain regions. Among HIV-infected individuals, the researchers noted a direct association between the severity of the infection and greater loss of brain matter. In methamphetamine abusers who are also HIV- positive, decreased volumes are correlated with increased cognitive impairment in one brain region, the hippocampus.

29. –33 year old man, high on methamphetamine admitted to emergency room complaining of severe headache in Portland Oregon. –X-ray revealed 12, 2 inch nails (6 on each side) in his head, administered with aq nail gun. –The man at first claimed it was an accident, but he later admitted that it was a suicide attempt. The nails were removed, and the man survived without any serious permanent damage. –He was eventually transferred to psychiatric care; he stayed for almost one month under court order but then left against doctors’ orders MSNBC-TV

30. MA Psychosis Inpatients from 4 Countries Psychotic symptomLifetimeCurrent Persecutory delusion Auditory hallucinations Strange or unusual beliefs Thought reading Visual hallucinations Delusion of reference Thought insertion or made act Negative psychotic symptoms Disorganized speech Disorganized or catatonic behavior 130 (77.4) 122 (72.6) 98 (58.3) 89 (53.0) 64 (38.1) 56 (33.3) 35 (20.8) 75 (44.6) 39 (23.2) 27 (16.1) 38 (22.6) 20 (11.9) 18 (10.7) 36 (21.4) 19 (11.3) 14 (8.3) No. of patients having symptoms (%) Srisurapanont et al., 2003

31. MA Psychosis 69 physically healthy, incarcerated Japanese females with hx MA use –22 (31.8%) no psychosis –47 (68.2%) psychosis 19 resolved (mean=276.2±222.8 days) 8 persistent (mean=17.6±10.5 months) 20 flashbackers (mean=215.4±208.2 days to initial resolution) –11 single flashback –9 Recurrent flashbacks Yui et al., 2001 Polymorphism in DAT Gene associated with MA psychosis in Japanese Ujike et al., 2003

32. Prenatal Meth. Exposure Preliminary findings on infants exposed prenatally to methamphetamine (MA) and nonexposed infants suggest: –Prenatal exposure to MA is associated with an increase in SGA (Small-for-Gestational-Age). –Neurobehavioral deficits at birth were identified in NNNS (Neonatal Intensive Care Unit Network Neurobehavioral Scale) neurobehavior, including dose response relationships and acoustical analysis of the infant’s cry (Lester et al., 2005).

33. Adolescent Meth. Abuse Treatment Admissions Matrix (Boys) (Girls) –2002 16%63% –2003 25%67% –2004 22%69% Phoenix (Boys) (Girls) –2002 25%43% –2003 23%51% –2004 27%53%

34. My Sexual Pleasure is Enhanced by the use of: (Rawson et al., 2002)

35. My Sexual Performance is Improved by the use of: (Rawson et al., 2002)

36. Female Methamphetamine Users: Social Characteristics and Sexual Risk Behavior Semple SJ, Grant I, Patterson TL Women and Health Vol. 40(3), 2004

37. Introduction In San Diego county, a sizable percentage of meth users were welfare mothers who lived in subsidized housing. The majority of women had started using meth during their teenage years and had become long-term, chronic users.

38. Introduction Another study reported that women’s motivations for using meth centered on: –Weight loss –Enhanced self-confidence –Increased energy for dealing with demands of childrearing and household activities –Enhanced sexual pleasure Other studies have also reported that women, like men, experience: –Increased sexual desire and sex drive –Prolonged sexual activity associated with meth use

39. 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%)

40. Sexual Partners of Meth-Using Women On average women had 7.8 sexual partners in a two-month period (SD=10.7, range 1-74). 84% had casual partners during the past two months. –90% of all casual partners were reported to be meth users. 31% had an anonymous partner in the past two months. –76% of anonymous sex partners were meth users. No spouses or live-in partners were reported to be HIV-positive.

41. Sexual Risk Behavior Participants engaged in an average of 79.2 sex acts over a two-month period. Most sexual activity was unprotected. The average number of unprotected and protected sex acts over the two-month period was 70.3 and 8.8, respectively. In terms of unprotected sex: –56% of all vaginal sex acts were unprotected –83% of all anal sex acts were unprotected –98% of all oral sex acts were unprotected

42. Social Networks and Meth Use The influence of social network on the meth use of women represents another understudied area of research. For the most part, women’s sexual partners were also meth users. Not surprisingly, the sexual enhancement properties of meth make it a drug that is used most often with a sexual partner. Research on drug-using women has shown an association between partners’ use of drugs and women’s experience of physical abuse and sexual coercion.

43. Social Networks and Meth Use It is plausible that the drug use behaviors and sexual risk practices of some meth-using women are influenced by perceived threats from drug-using male partners. Data also suggests that women limit their meth use to private locations, and use primarily with sexual partners and friends. Thus, unless women’s meth use is exposed through an event, such as an encounter with law enforcement, they are likely to remain hidden for long periods of time.

44. Treatment

45. Treatment Outcomes for AI/AN in LA County 2005 Drug CategoryDays of Use Admission Discharge Alcohol 14.15.4 Cocaine 13.13.7 Heroin 19.1 10.5 Methamphetamine 12.03.0

46. Methamphetamine Treatment Statistics Drop out rates Retention in treatment rates Re-incarceration rates Other measures of outcome All these measures indicate that MA users respond in an equivalent manner as individuals admitted for other drug abuse problems. Analysis of data from 3 other large data sets and 3 clinical trials data sets suggest treatment response (using psychosocial treatments) of MA and cocaine users is indistinguishable.

47. Why the “MA Treatment Does Not Work” Perceptions? Many of the geographic regions impacted by MA do not have extensive treatment systems for severe drug dependence. Medical and psychiatric aspects of MA dependence exceeds program capabilities. High rate of use by women, their treatment needs and the needs of their children can be daunting. Although some traditional elements may be appropriate, many staff report feeling unprepared to address many of the clinical challenges presented by these patients

48. Special Treatment Consideration Should Be Made for the Following Groups of Individuals: 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. Individuals under the age of 21. Gay men (at very high risk for HIV and hepatitis).

49. Behavioral/Cognitive Behavioral Treatments Cognitive/Behavioral Therapy-CBT Motivational Interviewing-MI Contingency Management-CM 12-Step Facilitation Therapy Community Reinforcement Approach-CRA Matrix Model of Outpatient Treatment

50. Thank you rrawson@mednet.ucla.edu www.uclaisap.org www.methamphetamine.org rrawson@mednet.ucla.edu www.uclaisap.org