1. Prevention Research (Children & Adolescents) genetics environment development co-morbidity Prevention Research (Children & Adolescents) genetics environment development co-morbidity Priority Areas for NIDA

2. First Marijuana Use, (Percent of Initiates) 1.5% 67% 5.5% <12 12-17 18-25>25 Addiction is a Developmental Disease: It Starts Early 26%

3. Basic Science Tells Us that Adolescents’ Brains Are Still Developing… Basic Science Tells Us that Adolescents’ Brains Are Still Developing…

4. Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time

5. When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000.

6. Do Adolescents React Differently than Adults to Substances of Abuse?

7. Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2

8. Do We Need Fundamentally Different Strategies At Different Stages of Adolescence? Do We Need Fundamentally Different Strategies At Different Stages of Adolescence?

9. Why do some people become addicted while others do not? Vulnerability

10. We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex We Know There’s A Big Genetic Contribution To Drug Abuse and Addiction… And the Nature of this Contribution Is Extremely Complex

11. high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level

12. Becomes Subordinate Stress remains Individually Housed Group Housed Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs * * S.003.01.03.1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Dominant No longer stressed

13. What Other Environmental Factors Contribute to Addiction? Co-morbid mental illness Early physical or sexual abuse Witnessing violence Stress Peers who use drugs Drug availability

14. COMORBIDITY Example: SMOKING EPIDEMIOLOGY normal population: 23% alcoholism: 90%+ other addictions:90%+ schizophrenia: 85% depression: 80%

15. Why do Mental Illnesses and Substance Abuse Co-occur? Self-medication hypothesis –substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse –Substance abuse may increase vulnerability to mental illness Common or correlated causes –the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap

16. Prevention Works

17. Source: Monitoring the Future Study, 2003. Changes in Attitudes Lead to Changes in Use Changes in Attitudes Lead to Changes in Use

18. Treatment Interventions (New Targets & New Strategies) Treatment Interventions (New Targets & New Strategies) Priority Areas for NIDA

19. Source: Adapted from Volkow et al., Neuropharmacology, 2004. Drive Saliency Memory Control Non-Addicted Brain NO GO Addicted Brain Drive Memory Control GO Saliency Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits

20. This is why treatment is essential This is why addicts can’t just quit

21. Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) We Need to Treat the Whole Person! In Social Context Behavioral Therapies Medical and Social Services

22. Treatment Can Work

23. Genetics Mechanisms Treatments We Are Using Science to Develop Even Better Treatments We Are Using Science to Develop Even Better Treatments

24. Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CB1 Antagonists Inhibitors of metabolizing enzymes Inhibitors of metabolizing enzymes CRF Antagonists Medication Basic Research Agonist Therapy Methadone Buprenorphine Agonist Therapy Methadone Buprenorphine

25. But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma McLellan et al., JAMA, 2000.

26. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses Drug Addiction Type I Diabetes 0 10 20 30 40 50 60 70 80 90 100 Hypertension Asthma 40 to 60% 30 to 50% 50 to 70% Percent of Patients Who Relapse McLellan et al., JAMA, 2000.

27. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning-- is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore…

28. Full recovery is a challenge but it is possible …

29. DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent)

30. Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free

31. We Need to Keep Our Eye on the Real Target the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction…

32. Priority Areas for NIDA HIV/AIDS Research

33. Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease

34. Seronegative HIV HIV + Drug Acceleration of HIV Degeneration of Dopamine Cells With Cocaine

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

36. International Research Collaboration International Research Collaboration NIDA International Program Components NIDA International Program Components Post-Doctoral Research Fellowship Technical Consultation Technical Consultation Scientific Exchange Scientific Exchange Information Dissemination

37. Why focus on drug abuse internationally? I.Drug abuse is a global phenomenon 5 percent of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky Sexual Behaviors Related to Drug Abuse UNODC 2005 World Drug Report III. Take advantage of unique opportunities to advance scientific knowledge through research

38. NIDA Supports International Drug Abuse Research In Numerous Ways Fund international research Provide training and exchange opportunities Set international research priorities Organize & sponsor conferences and meetings Binational agreements Dissemination of information

39. Where Do We Need to Go From Here? Where Do We Need to Go From Here? We Need to… Advance the SCIENCE Erase the STIGMA and to… Erase the STIGMA and to…

40. For More Information NIDA Public Information: www.nida.nih.gov www.drugabuse.gov NIDA International Program: www.international.drugabuse.gov www.drugabuse.gov