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

Addiction as a Brain Disease:. Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health. High. Low. ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function. Decreased Brain Metabolism in Drug Abuse Patient.

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

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  1. Addiction as a Brain Disease: Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health

  2. High Low ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function Decreased Brain Metabolism in Drug Abuse Patient Control Cocaine Abuser Decreased Heart Metabolism in Heart Disease Patient Healthy Heart Diseased Heart Sources: From the laboratories of Drs. N. Volkow and H. Schelbert

  3. Biology/Genes Environment Beth Carter Richard Hill Alice Benson Rebecca Wilson Mary Walters Susan Edwards Allison Fields Edward Bryson JonathanCook Thomas Jones EdwardSmith William Price JaneJones Steven Adams Amy Mason John Walker DRUG Walter Jones John Smith Alice Price James Hill Susan Adams JaneWalker JamesCook Beth Bryson AnneCook Mary Hill ThomasSmith John Jones Ann Jones James Smith Brain Mechanisms John Smith Addiction ADDICTION INVOLVES MULTIPLE FACTORS

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

  5. Dopamine D2 Receptors are Lower in Addiction DA DA Cocaine DA DA DA DA DA DA DA DA DA DA Reward Circuits Non-Drug Abuser Meth DA D2 Receptor Availability DA DA DA Alcohol DA DA DA Reward Circuits Drug Abuser Heroin Adapted from Volkow et al., Neurobiology of Learning and Memory 78:610-624, 2002. control addicted

  6. Effects of Tx with an Adenovirus Carrying a DA D2 Receptor Gene into NAc in DA D2 Receptors Overexpression of DA D2 receptors reduces alcohol self-administration 60 1st D2R Vector 2nd D2R Vector p < 0.0005 50 p < 0.0005 40 Percent Change in D2R p < 0.005 p < 0.005 30 20 p < 0.10 10 Null Vector 0 6 10 4 8 24 0 0 -20 DA DA % Change in AlcoholIntake -40 p < 0.01 DA DA DA p < 0.01 -60 DA p < 0.001 DA DA -80 p < 0.001 p < 0.001 -100 0 4 6 8 10 24 Time (days) Thanos, PK et al., J Neurochem, 78, pp. 1094-1103, 2001.

  7. Effects of a Social Stressor on Brain DA D2 Receptors and Propensity to Administer Drugs Individually Housed Group Housed Dominant Subordinate 50 Becomes Dominant No longer stressed 40 Reinforcers (per session) 30 * * Isolation Can Change Neurobiology 20 10 Becomes Subordinate Stress remains 0 S .003 .03 .1 .01 Cocaine (mg/kg/injection) Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002.

  8. ADDICTION CONTRIBUTES TO MANY SERIOUS MEDICAL CONSEQUENCES • Mental Illness • Cancer • Infectious Diseases • (HIV, HCV) • Cardiac • Pulmonary • Learning Disorders • Obesity • Cerebrovascular • (strokes) • Trauma • (accidents)

  9. ADDICTION CAN BE TREATED Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 ml/gm METH Abuser (1 month detox) Normal Control METH Abuser (14 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

  10. Among IDUs the Most Effective HIV/AIDS Prevention Strategy is Drug Abuse Treatment HIV Seroconversion at 18 MonthsBy Receipt of Treatment 25 No treatment 20 Partial treatment 15 Rate of Seroconversion (%) Continuous treatment 10 5 0 Treatment Status Source: Metzger, D. S., Woody, G. E., McLellan, A. T., O’Brien, C. P., Druley, P., Navaline, H., De Philipps, D., Stolley, P., & Abrutyn, E. (1993). Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. Journal of Acquired Immune Deficiency Syndromes, 6, 1049-1056.

  11. Non-Addicted Brain Control STOP Saliency Drive Cycloserine Memory Medications for Relapse Prevention Vaccines Enzymatic degredation Naltrexone DA D3 antagonists CB1 antagonists AddictedBrain Interfere with drug’s reinforcing effects Control Biofeedback Modafinil Bupropion Stimulants Executive function/ Inhibitory control GO Adenosine A2 antagonists DA D3 antagonists Strengthen prefrontal- striatal communication Drive Saliency Interfere with conditioned memories (craving) Antiepileptic GVG N-acetylcysteine Memory Teach new memories Counteract stress responsesthat lead to relapse CRF antagonists Orexin antagonists

  12. Control Control CG STOP Saliency Saliency Drive Drive Drive OFC Saliency NAc GO Memory Memory Memory Amygdala Addicted Brain Non-AddictedBrain Adapted from: Volkow et al., J Clin Invest 111(10):1444-1451, 2003.

  13. 10 8 6 4 2 NI CI Self-report Craving (1-10) No-Inhibition (NI) Cognitive-Inhibition (CI) *** Before After pu < 0.001 Cocaine abusers, when directed, can inhibit cue-induced craving and decrease limbic activity

  14. Hipp NAcc VP Amyg MULTIPLE BRAIN CIRCUITS ARE INVOLVED IN ADDICTION EXECUTIVE FUNCTION PFC ACG INHIBITORY CONTROL OFC REWARD SCC MOTIVATION/ DRIVE MEMORY/ LEARNING

  15. Mapping Drug Risk Factors in a Community • Poor family • support • Drug availability • Poverty • Crime What are the neurobiological factors that mediate social stressors as a risk factor for drug abuse?

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