Presentation on theme: "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."— Presentation transcript:
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 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
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. Convergence of HIV Seroprevalence Among IDU and Non-IDU among Selected Cities
a p < 0.05 b p < 0.005 c p < 0.001 Intravenous Methylphenidate Increased Sexual Desire in Cocaine Abusers and Controls Volkow ND et al., AJP 2007 164: 157-160.
Key Brain Structures of the Impulsive (red) and the Controlling Systems (blue) Bechara A Nature Neuroscience 8, 1458 - 1463 (2005).
Alcohol decreased activity of areas involved with control and increased activity of areas involved with impulsivity Decreases prefrontal cortex cingulate gyrus Increases Amygdala, NAcc Zhu et al., Alcohol Alcohol 39: 53-58 2004. Effects of Alcohol Intoxication on Brain Glucose Metabolism (Marker of Brain Function)
Chronic Drug Effects – Disruption of Inhibitory Control DA signal DA D2 Receptors Metabolism
Dopamine D2 Receptors are Lower in Addiction DA D2 Receptor Availability Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth control addicted Adapted from Volkow et al., Neurobiology of Learning and Memory 78:610-624, 2002.
In Methamphetamine Abusers Low Striatal DA D2/D3 Receptor Availability Is Associated with Impulsivity Lee, B. et al. J. Neurosci. 2009. Impulsivity (z-score) D2/D3 Receptors BP (Z-score) -3 -2 -1 0 1 2 3
Correlations Between D2 Receptors in Striatum and Brain Glucose Metabolism Striatum CG PreF OFC 30 35 40 45 50 55 60 65 1.8126.96.36.199.833.23.4 DA D2 Receptors (Ratio Index) OFC umol/100g/min r = 0.7, p < 0.001 30 40 50 60 70 80 90 2.9188.8.131.52.43.53.6 OFC umol/100gr/min DA D2 Receptors(Bmax/kd) Cocaine Abusers r = 0.7, p < 0.005 METH Abusers control cocaine abuser Volkow et al., AJP 158(3):377-382, 2001.
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
Chang et al., Neuroimage, 42:869-78, 2008. Some Psychoactive Drugs Exacerbate Neurotoxic Effects of HIV
HIV Seroconversion at 18 Months By Receipt of Treatment 0 0 5 5 10 15 20 25 Rate of Seroconversion (%) Treatment Status No treatment Partial treatment Continuous treatment 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. Among IDUs the Most Effective HIV/AIDS Prevention Strategy is Drug Abuse Treatment
Krupitzky et al., unpublished Placebo: N=124 XR-NTX: N=126 IM Injection every 4 weeks for 24 weeks Future Research Long-Acting Injectable Medications (i.e., Depot Naltrexone)
Binding Site Capillary Blood Flow Brain Antibodies VACCINE Antibodies Can Reduce Brain Concentrations Future Research Immunotherapies for Addiction Treatment (i.e., Vaccines) Capillary Blood Flow Brain Targeting the drugs, not the receptors
## 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 Heroin 1 mg/kg, s.c. 30 min Hot Plate Test The Vaccine(s) New Heroin Vaccine(s) K.D. Janda & G.F. Koob Laboratories at TSRI
Drive OFC Drive OFC Saliency NAc Saliency NAc Memory Amygdala Memory Amygdala Control CG Control CG Non-Addicted Brain Addicted Brain STOP GO Drive Memory Saliency Control Drive Memory Saliency Adapted from: Volkow et al., J Clin Invest 111(10):1444-1451, 2003. Adapted from: Volkow et al., J Clin Invest 111(10):1444-1451, 2003.
Medications for Relapse Prevention Addicted Brain Drive Control Saliency Memory GO Strengthen prefrontal- striatal communication Strengthen prefrontal- striatal communication Executive function/ Inhibitory control Executive function/ Inhibitory control Interfere with conditioned memories (craving) Interfere with conditioned memories (craving) Teach new memories Counteract stress responses that lead to relapse Interfere with drug’s reinforcing effects Interfere with drug’s reinforcing effects Vaccines Enzymatic degredation Naltrexone DA D3 antagonists CB 1 antagonists Vaccines Enzymatic degredation Naltrexone DA D3 antagonists CB 1 antagonists Biofeedback Modafinil Bupropion Stimulants Biofeedback Modafinil Bupropion Stimulants Antiepileptic GVG N-acetylcysteine Antiepileptic GVG N-acetylcysteine Cycloserine CRF antagonists Orexin antagonists CRF antagonists Orexin antagonists STOP Drive Control Memory Non-Addicted Brain Saliency Adenosine A2 antagonists DA D3 antagonists Adenosine A2 antagonists DA D3 antagonists
Rates (%) of Positive Urines for Cocaine Metabolites Gerra G et al., J Psychopharmacol Online First January 9, 2006. 36.67 40 41.67 18.18 33.33 9.09 --Naltrexone Alone--Naltrexone + Buprenorphine Naltrexone & Buprenorphine in the Treatment of Cocaine Dependence
Dalley JW et al., Science 315, 1267 (2007). Impulsive Rats Have Lower D2R in Striatum