Bringing the Full Power of Science to Bear on

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

2. Addiction Medical Medical Neurotoxicity AIDS, Cancer Mental illness NEUROTOXICITY AIDS CANCERMENTAL ILLNESS DRUGS Economic Social Health care Productivity Accidents 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. 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 Your Brain on Drugs Today YELLOW shows places in brain where cocaine binds (striatum) Front of Brain Back of Brain Fowler et al., Synapse, 1989.

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

10. Addiction Involves Multiple Factors

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

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

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

14. Dopamine motivation Reward& well-being addiction movement

15. Drugs are “Imposters” of Brain Messages

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

18. dopamine transporters

19. 15 10 Copulation Frequency 5 0 Mounts 1 2 3 4 5 6 7 8 Intromissions Ejaculations Natural Rewards Elevate Dopamine Levels SEX FOOD 200 200 NAc shell 150 150 DA Concentration (% Baseline) 100 100 % of Basal DA Output Empty 50 Box Feeding 0 0 60 120 180 Female Present Time (min) Sample Number Di Chiara et al., Neuroscience, 1999. Fiorino and Phillips, J. Neuroscience, 1997.

21. Effects of Drugs on Dopamine Release COCAINE AMPHETAMINE Accumbens 1100 Accumbens 400 1000 900 DA 800 DA 300 DOPAC 700 DOPAC HVA % of Basal Release HVA 600 % of Basal Release 500 200 400 300 100 200 100 0 0 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine NICOTINE MORPHINE 250 Accumbens 250 Dose (mg/kg) 200 Accumbens 0.5 200 Caudate 1.0 2.5 150 % of Basal Release 10 150 % of Basal Release 100 0 1 2 3 hr 100 0 1 2 3 4 5 hr 0 0 0 1 2 3 4 5hr Time After Nicotine Time After Morphine Di Chiara and Imperato, PNAS, 1988

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

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

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

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

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

28. 2.0 1.8 1.6 1.4 1.2 Dopamine Transporter Time Gait Bmax/Kd 1.0 7 8 9 10 11 12 13 (seconds) 2.0 1.8 1.6 1.4 1.2 Delayed Recall (words remembered) 1.0 16 14 12 10 8 6 4 Dopamine Transporters in Methamphetamine Abusers Motor Task Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. Normal Control Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment. Volkow et al., Am. J. Psychiatry, 2001. Methamphetamine Abuser

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