1. Methamphetamines University of Pittsburgh Graduate

2. Learning objectives 1.To provide a historical context of methamphetamine use and abuse 2.To overview medicinal uses of methamphetamine 3.To discuss mechanisms and outcomes of methamphetamine abuse 4.To discuss the challenges of methamphetamine research

3. What is methamphetamine? Formula C10H15 N Molecular mass: 149.233 g/mol Half life: 9-15 hours Excretion: renal

4. What is methamphetamine? Source – NIDA Research Report – 1998

5. History of meth Amphetamine created in Germany in 1887 Used widely during WWII by the Nazi and Japanese armies Japanese kamikaze pilots were documented to be high on meth Major challenge in postwar Japan Biker gangs in California after WWII began to distribute meth Source – Nebraska State Patrol

6. Methamphetamine: medical uses Narcolepsy Attention deficit disorder Obesity (short term use)

7. Forms of Distribution

8. What does meth look like? Typically an odorless powder that dissolves quickly in water Another form of meth is clear chunky crystals referred to as crystal meth or ice May be in the form of small brightly colored tablets, referred to as YABA

9. How is meth used? Injected Snorted Smoked Orally

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

11. Meth causes… Increased alertness Decreased appetite A distorted sense of well- being Effects that can last 8 to 24 hours

12. U.S. Emergency Dept. Mentions of Meth/amphetamines 1995-2002 DAWN, July 2004

13. Demographics of MA-related ED visits in U.S., 2002 58% male and 42% female Race/ethnicicty White65% Latino11% African American6% Age Under 18 11% 18-34 years56% Over 34 33% DAWN, 2004

14. Behavior changes Health changes Psychotic behavior Paranoia Aggression Anxiety Fatigue Depression Delusions Mood swings Confusion Insomnia Hallucinations Stroke Brain damage Weight loss Death Source – Congressional Research Sites

16. How does methamphetamine work? Methamphetamine releases large amounts of dopamine in the brain, causing feelings of pleasure and euphoria. Source: National Institute on Drug Abuse. April 1998, Reprinted January 2002. Research Report Series: Methamphetamine Abuse and Addiction. www.nida.nih.gov/ResearchReports/methamph/methamph.html

17. Researchers report that the dopamine-producing cells in the brain can be damaged after prolonged exposure to relatively low levels of methamphetamine. Effects of meth on dopamine

18. 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

19. 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 0 100 200 300 400 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 Effects of Drugs on Dopamine Levels

20. PET Scan of Long-Term Meth Brain Damage

21. Long-term effects: What will happen in the future Methamphetamine destroys the endings of dopamine containing nerve cells (NIDA 2)

22. Partial Recovery of Brain from Methamphetamine After Abstinence Normal Control METH Abuser (1 month abstinent) METH Abuser (14 months abstinent) 0 3 ml/gm Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001. Dopamine improvements after 1 year, but not cognitive and motor functioning

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

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

25. Highly Toxic Substances Drain cleaner Battery acid Antifreeze Over-the-counter asthma medicine containing ephedrine or pseudoephedrine Match-box striker (Red phosphorous) Hydrochloric acid Lye Lantern fuel (KCI)

26. Methamphetamine use and pregnancy Possible effects found in the few human studies that exist include increased rates of premature delivery, placental abruption (early separation of a normal placenta from the wall of the uterus), retarded fetal growth, and cardiac and brain abnormalities. Source: Volkow, Nora, M.D., Director, NIDA. April 21, 2005. Testimony Before the Subcommittee on Labor, Health, and Human Services; Education; and Related Agencies. Committee on Appropriations, U.S. Senate. www.hhs.gov/asl/testify/t050425b.html

27. Meth Mouth: Myth and Reality

28. How many Americans use methamphetamines? Lifetime use: 4.9 percent of those aged 12 and over (12 million people) Past-year use: 0.6 percent of those aged 12 and over (1.4 million people) Past-month use: 0.2 percent of those aged 12 and over (600,000 people) Source: The Substance Abuse and Mental Health Services Administration/Office of Applied Studies. September 16, 2005. The NSDUH Report: Methamphetamine Use, Abuse, and Dependence: 2002, 2003, and 2004, In Brief. http://oas.samhsa.gov/2k5/meth/meth.htm

29. Environmental effects of meth Meth production leaves behind 5 to 6 pounds of toxic waste per pound of meth produced. Toxic by-products contaminate sites where meth is produced, posing serious health and environmental hazards to those nearby. The cost to clean up one meth lab often exceeds $4,000. Source – Koch Crime Institute

30. Impacts on families Danger of children being exposed to toxic fumes Children are more at risk than adults to environmental hazards, as their bodies are immature Risk of explosion, fire, and chemical burns Exposure to weapons, finished drugs, and unsanitary conditions

31. More impacts on families Increase in child abuse and neglect cases Increased risk for substance abuse among children in later life A rise in domestic disputes

32. Is there an effective treatment for methamphetamine abuse? At this time the most effective treatments for methamphetamine addiction are cognitive behavioral interventions. These approaches are designed to help modify the patient's thinking, expectancies, and behaviors and to increase skills in coping with various life stressors. Methamphetamine recovery support groups also appear to be effective adjuncts to behavioral interventions that can lead to long-term drug-free recovery.

33. U.S. admissions for MA drug treatment SAMSHA, 2004

34. Epidemiology High prevalence of HIV in patients who use crystal MA Shoptaw, et al, J Addict Dis 2002 showed in a CA study that 61% of men seeking tx for MA had HIV infection –77% of men were white, 17% were Latino –All were in their mid 30’s and had some college education –Reported a mean of 66 different partners in 6 months –Persons with HIV were more likely to have injected MA, contracted an STD and had more UAI Klitzman, et al Am J Psychiatry 2000 reported strong association between MDMA use and high-risk sexual behavior 2001 report in MMWR found that in an outbreak of 130 cases of syphilis in CA, 51% were MSM and 18% reported use of MA

35. Epidemiology Study of 25 HIV+ gay men using MA (Semple et al., J Subst Abuse Treat 2002) –“provided temporary escape from being HIV+” –“helps manage negative self-perception and social rejection associated with being HIV+ –“method of coping with the specter of death”

36. Key points on methamphetamine Methamphetamine is a drug that can be effectively used for several medical conditions When used illegally, Meth is a powerful, highly addictive stimulant that can be made easily from legally available products. Twelve million Americans ages 12 and over have used meth at least once; use is most common between ages 19 and 40. Meth labs use and produce toxic, explosive chemicals; meth labs are dangerous and expensive to clean up. Exposure to chemicals used to make meth may cause cancer, damage the brain and other organs, and result in birth defects.