1. Bringing the Full Power of Science to Bear on Bringing the Full Power of Science to Bear on NIDA NATIONAL INSTITUTE ON DRUG ABUSE Drug Abuse & Addiction Drug Abuse & Addiction

2. NEUROTOXICITY AIDS CANCER MENTAL ILLNESS NEUROTOXICITY AIDS CANCER MENTAL ILLNESS Neurotoxicity AIDS, Cancer Mental illness Neurotoxicity AIDS, Cancer Mental illness Health care Productivity Accidents Health care Productivity Accidents Homelessness Crime Violence Homelessness Crime Violence

3. 4 Out of 10 U.S. AIDS Deaths Are Related to Drug Abuse

4. Estimated Economic Cost to Society from Substance Abuse and Addiction: Illegal drugs: $181 billion/year Alcohol: $185 billion/year Tobacco: $158 billion/year Total: $524 billion/year Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.

5. What is Addiction? Addiction is A Brain Disease Characterized by compulsive behavior The continued abuse of drugs despite negative consequences A chronic, potentially relapsing disorder

6. Advances in science have revolutionized our fundamental views of drug abuse and addiction.

7. used to be

8. Your Brain on Drugs Today 1-2 Min3-45-6 6-77-88-9 9-1010-2020-30 YELLOW shows places in brain where cocaine binds (striatum) Front of Brain Back of Brain Fowler et al., Synapse, 1989.

9. Healthy Heart Diseased Heart Decreased Heart Metabolism in Heart Disease Patient Diseased Brain/ Cocaine Abuser High Low Addiction is Like Other Diseases…  It is preventable.  It is treatable  It changes biology.  If untreated, it can last a lifetime. Research supported by NIDA addresses all of these components of addiction Healthy Brain Decreased Brain Metabolism in Drug Abuser

10. Addiction Involves Multiple Factors

11. that starts in adolescence and childhood National Epidemiologic Survey on Alcohol and Related Conditions, 2003. National Epidemiologic Survey on Alcohol and Related Conditions, 2003. Age Age attobacco,alcoholandcannabisdependence per DSM IV 0.0% 0.2% 0.4% 0.6% 0.8% 1.0% 1.2% 1.4% 1.6% 1.8% 5 5 10 15 21 25 30 35 40 45 50 55 60 65 % in each age group who develop first-time dependence first CANNABIS ALCOHOL TOBACCO Addiction Is A Developmental Disease

12. Why Do People Take Drugs in The First Place? To feel good To have novel: feelings sensations experiences AND to share them To feel better To lessen: anxiety worries fears depression hopelessness

13. Drugs of Abuse Engage Systems in the Motivation and Pleasure Pathways of the Brain Drugs of Abuse Engage Systems in the Motivation and Pleasure Pathways of the Brain Why Do People Abuse Drugs? Why Do People Abuse Drugs?

14. addiction Reward & well-being motivation Dopamine movement

15. Drugs are “Imposters” of Brain Messages

16. Donald Bliss, MAPB, Medical Illustration The Neuron: How the Brain’s Messaging System Works Terminal branches of axon Cell body (the cell’s life support center) Dendrites Axon Myelin sheath Neuronal Impulse

18. dopamine transporters

19. 0 50 100 150 200 060120180 Time (min) % of Basal DA Output NAc shell Empty BoxFeeding Di Chiara et al., Neuroscience, 1999. FOOD Mounts Intromissions Ejaculations Fiorino and Phillips, J. Neuroscience, 1997. Natural Rewards Elevate Dopamine Levels 100 150 200 DA Concentration (% Baseline) 15 0 5 10 Copulation Frequency Sample Number 12345678 SEX Female Present

21. 0 100 150 200 250 0123 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Di Chiara and Imperato, PNAS, 1988 Effects of Drugs on Dopamine Release

22. Other neurotransmitter systems are also affected: Other neurotransmitter systems are also affected: But Dopamine is only Part of the Story Serotonin: mood regulation, sleep Glutamate: learning and memory

24. Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways Science Has Generated Much Evidence Showing That…

25. We Have Evidence That These Changes Can Be Both Structural and Functional We Have Evidence That These Changes Can Be Both Structural and Functional AND…

26. Amph NA C Saline Source: Robinson & Kolb, Journal of Neuroscience, Volume: 1997 Structurally…

27. DA D2 Receptor Availability Control Addicted Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction DA Functionally…

28. Dopamine Transporters in Methamphetamine Abusers Normal Control Methamphetamine Abuser Motor Task Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment. 78910111213 1.0 1.2 1.4 1.6 1.8 2.0 Time Gait (seconds) 46810121416 1.0 1.2 1.4 1.6 1.8 2.0 Delayed Recall (words remembered) Dopamine Transporter Bmax/Kd Volkow et al., Am. J. Psychiatry, 2001.

29. Implication: Brain changes resulting from prolonged use of drugs may compromise mental and motor functions

30. Circuits Involved In Drug Abuse and Addiction All of these must be considered in developing strategies to effectively treat addiction