Nora D. Volkow, M.D. Director National Institute on Drug Abuse

1. Research on METHAMPHETAMINE Where Do We Need To Go? Nora D. Volkow, M.D. Director National Institute on Drug Abuse

2. In 2003, over 12.3 million people age 12 or older reported having used methamphetamine at least once in their lifetime BUT Is methamphetamine abuse increasing? Source: 2003 NSDUH, SAMHSA

3. According to the Monitoring the Future Study… Methamphetamine is not Increasing * P < .05 Percent of Students Reporting Use of Methamphetamine in Past Year, by Grade

4. Methamphetamine Treatment Admissions Have Been Increasing 60 50 40 30 20 10 0 52 42 36 32 32 32 30 Per 100,000 Aged 12 or Older 25 22 14 10 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 Methamphetamine/Amphetamine Treatment Admission Rate : 1992 -2002 2002 SAMHSA Treatment Episode Data Set

5. Concerns with Methamphetamine • Neurotoxic in animal models of drug self administration • Highly addictive • Intoxication associated with behaviors that increase risks for infection with HIV and HCV • Can be easily manufactured by small clandestine laboratories

6. 1500 1000 500 0 METHAMPHETAMINE % of Basal Release 0 1 2 3hr Time After Methamphetamine COCAINE 500 400 300 % of Basal Release 200 100 0 0 1 2 3 4 5 hr Time After Cocaine Dopamine Neurotransmission frontal cortex nucleus accumbens VTA/SN

7. Brain Dopamine System DA Transporters DA Receptors DA DA Anatomy DA DA DA DA DA signal Dopamine Cell Metabolism

8. 2.4 2.2 2 Dopamine Transporters Normal Control 1.8 1.6 1.4 1.2 1 Methamphetamine Abuser Dopamine Transporters in Methamphetamine Abusers (Bmax/Kd) Normal Meth Controls Abusers p < 0.0002 Methamphetamine abusers have significant reductions in dopamine transporters BNL UCLA SUNY

9. The Abnormalities are Similar Though Less Severe Than Those in Parkinson’s Disease Could METH abuse increase the risk of Parkinson’s disease as people grow older?

10. 2.0 1.8 1.6 1.4 1.2 1.0 7 8 9 10 11 12 13 2 1.8 1.6 1.4 1.2 1 16 14 12 10 8 6 4 Dopamine Transporters in Methamphetamine Abusers Motor Task Loss is associated with slowing of motor reactions. (Bmax/Kd) Dopamine Transporter Time Gait Memory Task (seconds) Loss is associated with memory impairment. Dopamine Transporter Bmax/Kd BNL/UCLA/SUNY Delayed Recall (words remembered) NIDA, DOE (OBER), ONDCP

11. 3 0 ml/gm Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence METH Abuser (1 month detox) Normal Control METH Abuser (24 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

12. Brain Dopamine System DA Transporters DA Receptors DA DA Anatomy DA DA DA DA DA signal Dopamine Cell Metabolism

13. Thalamus Caudate 1.20 1.10 1.00 0.90 0.80 1.30 0.70 Controls METH 1.20 1.10 1.00 0.90 0.80 0.70 Decreased Metabolism in Methamphetamine Abusers Region/Gray Matter) P < 0.001

14. METH abusers < controls Early Detoxification Late Detoxification (FWHM = 16mm, pixel threshold = 0.001)

15. How Can Science Help us Guide Prevention and Treatment Efforts? Research Has Shown that Adolescents Report Physical Appearance and Performance Abilities To Be Strong Motivators for Such Health-Related Behaviors As Quitting Smoking Source: Riedel, BW, Drug and Alcohol Dependence, 68, 167-174, 2002.

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

17. As we grow older we lose dopamine transporters in our brain; methamphetamine accelerates this loss 28 years Will affect motor reflexes 44 years Methamphetamine 28 years Will affect memory 84 years

18. Proportions of AIDS Cases in Adults and Adolescents by Exposure in the USA 70 60 50 40 30 20 10 0 Men who have sex with men (MSM) % of Cases Injection drug use Heterosexual contact MSM who inject drugs 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Year of Diagnosis Source: Centers for Disease Control and Prevention (CDC)

19. Methamphetamine in the HIV Epidemic • METH has been shown to alter immune function • Risky sexual behavior that occurs during METH • intoxication increases the risk of HIV infection • Physiological changes resulting from METH • use may increase infectivity (e.g., erosion of • normal protective epithelial layer)

20. Emergency Department (ED)Visits Involving Amphetamines/Methamphetamine Increased 54% Between 1995 and 2002 in the U.S. Source: OAS, SAMHSA, Drug Abuse Warning Network (DAWN), 2002 (03/2003 update).

21. Aggressive Action Is Needed To Stop METH Use & Its Serious Consequences We Need to Work TOGETHER To Make the Public Aware of the Drug’s Toxic and Addictive Properties And to Develop Treatments that will counteract neuroadaptations that underlie the addictive process and reverse METH’s neurotoxic effects

22. 2002 Data on Drug Treatment Admissions Indicate that in 16 US States METH Was the Primary Drug Problem at the Time of Admission…AND In 14 of These States There Were More Admissions Resulting From METH than from Heroin and Cocaine Combined Source: 2002 SAMHSA Treatment Episode Data Set

23. 55 50 45 40 35 30 25 20 Brain Glucose Metabolism in METH Abusers Whole Brain (micromol/100 gr/min) Metabolic Rate Controls METH p < 0.05 BNL, UCLA, SUNY

24. Brain Metabolism in METH Abusers with Abstinence 1.35 1.3 1.3 1.25 1.25 1.2 1.2 1.15 1.1 1.15 1.05 1 1.1 Short Protracted Short Protracted Thalamus Striatum Control Ratio METH Abuser (3 m Detox) +12±9%, p < 0.015 +2.7±6.7%, p = 0.34 METH Abuser (13 m Detox)

25. METH abusers > controls 5.0 Early Detoxification 4.0 3.0 Late Detoxification (FWHM = 16mm, pixel threshold = 0.001)