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DRUG ADDICTION: A Brain Disease Associated with High Risk Behavior

DRUG ADDICTION: A Brain Disease Associated with High Risk Behavior. Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health. Drug Use Has Played A Major Role in HIV Transmission. Convergence of HIV Seroprevalence Among IDU

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DRUG ADDICTION: A Brain Disease Associated with High Risk Behavior

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  1. DRUG ADDICTION: A Brain Disease Associated with High Risk Behavior Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health

  2. Drug Use Has Played A Major Role in HIV Transmission

  3. Convergence of HIV Seroprevalence Among IDU and Non-IDU among Selected Cities Non-injecting drug use appears to be an important factor contributing to HIV infection due to their high-risk behaviors and overlapping social and sexual networks with IDUs Strathdee and Stockman Curr HIV/AIDS Rep. 2010 7(2):99-106.

  4. Intravenous Methylphenidate Increased Sexual Desire in Cocaine Abusers and Controls a p < 0.05 b p < 0.005 c p < 0.001 Volkow ND et al., AJP 2007 164: 157-160.

  5. Key Brain Structures of the Impulsive (red) and the Controlling Systems (blue) Bechara A Nature Neuroscience 8, 1458 - 1463 (2005).

  6. Decreases prefrontal cortex cingulate gyrus Increases Amygdala, NAcc Effects of Alcohol Intoxication on Brain Glucose Metabolism (Marker of Brain Function) Alcohol decreased activity of areas involved with control and increased activity of areas involved with impulsivity Zhu et al., Alcohol Alcohol 39: 53-58 2004.

  7. Chronic Drug Effects • – Disruption of Inhibitory Control DA DA DA D2 Receptors DA DA DA DA DA signal Metabolism

  8. 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

  9. In Methamphetamine Abusers Low Striatal DA D2/D3 Receptor Availability Is Associated with Impulsivity Impulsivity (z-score) -3 -2 -1 0 1 2 3 D2/D3 Receptors BP (Z-score) Lee, B. et al. J. Neurosci. 2009.

  10. 90 80 70 60 50 40 30 2.9 3 3.1 3.2 3.3 3.4 3.5 3.6 Correlations Between D2 Receptors in Striatum and Brain Glucose Metabolism Cocaine Abusers 65 60 55 OFC CG 50 umol/100g/min 45 PreF Striatum 40 r = 0.7, p < 0.001 35 OFC 30 1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4 DA D2 Receptors (Ratio Index) METH Abusers OFC umol/100gr/min r = 0.7, p < 0.005 control cocaine abuser DA D2 Receptors (Bmax/kd) Volkow et al., AJP 158(3):377-382, 2001.

  11. What are the Mechanisms Underlying the Relationship Between Drug Use and HIV/AIDS? • Acute Drug Effects • – Drug Intoxication and Decision Making • Chronic Drug Effects • – Disruption of Inhibitory Control • Interaction of Drugs and HIV

  12. Some Psychoactive Drugs Exacerbate Neurotoxic Effects of HIV Chang et al., Neuroimage, 42:869-78, 2008.

  13. 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.

  14. Future Research Long-Acting Injectable Medications (i.e., Depot Naltrexone) IM Injection every 4 weeks for 24 weeks Placebo: N=124 XR-NTX: N=126 Krupitzky et al., unpublished

  15. Future Research Immunotherapies for Addiction Treatment (i.e., Vaccines) Antibodies Can Reduce Brain Concentrations VACCINE Binding Site Antibodies Targeting the drugs, not the receptors Capillary Blood Flow Capillary Blood Flow Brain Brain

  16. New Heroin Vaccine(s)K.D. Janda & G.F. Koob Laboratories at TSRI The Vaccine(s) Hot Plate Test Heroin 1 mg/kg, s.c. 30 min ##p<0.01, ###p<0.001, significant reduction of analgesia vs. Control/KLH group, ### p<0.001, significant reduction of analgesia vs. Control/KLH group

  17. 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.

  18. 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

  19. Naltrexone & Buprenorphine in the Treatment of Cocaine Dependence 41.67 --Naltrexone Alone --Naltrexone + Buprenorphine 40 36.67 33.33 Rates (%) of Positive Urines for Cocaine Metabolites 18.18 9.09 Gerra G et al., J Psychopharmacol Online First January 9, 2006.

  20. Impulsive Rats Have Lower D2R in Striatum Dalley JW et al., Science 315, 1267 (2007).

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