Neurobiological Advances in Addiction Science: Implications For Treatment Nora D. Volkow, M.D. Director
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1 Neurobiological Advances in Addiction Science: Implications For Treatment Nora D. Volkow, M.D.
2 Concentration ) Dopamine (nm) Drugs and Natural Rewards ACTIVATE Dopamine in Reward Regions ` METHAMPHETAMINE Dose (mg/kg IV) min Time After Methamphetamine SEX Nestler, Nature Neurosci, 2
3 Repeated Drug Use Changes the Brain Weakens the Brain Dopamine System Control Cocaine Abuser TYROSINE TYROSINE TYROSINE DOPA DOPA DOPA D A D A D A D A D A D A COCAINE D A D A PLEASURE REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES LEVELS OF DOPAMINE D2 RECEPTORS
4 Bmax/Kd D2 Receptors (Ratio Index) Dopamine D2 Receptors are Lower in Addiction. Normal Controls Cocaine Abusers Cocaine. 2. Meth Alcohol.2` Heroin 2 2 control addicted Volkow et al., Neuro Learn Mem
5 2nd D2R Vector Null Vector % Change in D2R 1st D2R Vector 2nd D2R Vector Effects of Increasing Brain D2 Receptors in Alcohol Drinking Behavior (Thanos et al., 21) D2 Receptors p <. p <. p <. p <.1 p < Time (days) -2 Alcohol Intake p <.1 p <.1 p <.1 p <.1 p < Time (days)
6 Frontal Metabolism Chronic Drug Use Reduces D2 Receptors Impairing Frontal Function signal D2 Receptors Metabolism Control Controls Metabolism CG (micromol/1g/min) Controls Cocaine Abuser Methamphetamine Abusers Alcoholics D2R VS (Bmax/Kd) Metabolism OFC (micromol/1g/min) D2 Receptors (BP ND ) D2R VS (Bmax/Kd) D2 Receptors (BP ND ). Metabolism Prefrontal
7 D2 Receptors and Relationship to Brain Metabolism in Subjects with Family History for Alcoholism OFC Relative metabolism CG Relative metabolism Correlations between Metabolism and D2R P <. Volkow et al. Arch Gen Psychiatry D2R (Bmax/Kd) D2R were associated with metabolism in PREFRONTAL regions the disruption of which results in impulsivity and compulsivity
8 John Smith James Smith Ann Jones ThomasSmith AnneCook John Jones Mary Hill John Smith EdwardSmith JaneWalker JamesCook Beth Bryson Walter Jones Alice Price James Hill Susan Edwards John Walker JaneJones JonathanCook Amy Mason Edward Bryson Beth Carter Thomas Jones Rebecca Wilson William Price Alice Benson Richard Hill Mary Walters Steven Adams Susan Adams Allison Fields Addiction Involves Multiple Factors DEVELOPMENT/Genes ENVIRONMENT DRUG Brain Mechanisms Addiction
9 Social Rank & Vulnerability to Drug Abuse Dominant months Dominant Subordinate Individual Housed Individual Housed Subordinate months Group Housed Group Housed 2 * * 1 S Cocaine (mg/kg/inj Morgan, D. et al. Nature Neuroscience, : , 22.
10 ADDICTION CAN BE TREATED Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence ml/gm Normal Control METH Abuser (1 month detox) METH Abuser (1 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, , 21.
11 Symptom Severity Symptom Severity Evaluation of A Hypothetical Treatment HYPERTENSION Pre During During During Post ADDICTION Pre During During During Post Stage of Treatment Just Like Hypertension, Addiction Is A Chronic Disease That Requires Continued Care Source: McLellan, AT, Addiction 97, 29-22, 22.
12 Opportunities with Health Care Reform to Expand Involvement of the Health Care System in Treatment of SUD In 21 An Estimated 21. Million Americans 12 or Older Were Dependent On Any Illicit Drugs or Alcohol Self Help Group Outpatient Rehab Outpatient Mental Health Center Location TX Received But Only.1 Million (19%) of These Individuals Had Received Some Type of Tx In the Past Year and few involved Health Care Systems Inpatient Rehab Hospital Inpatient Doctor s Office Emergency Room Prison or Jail Numbers in Millions Source: 21 NSDUH, National Findings, SAMHSA, OAS, 21.
13 Challenge: How to Integrate Drug Abuse & Addiction Screening, Prevention & Treatment into the Healthcare System
14 Non-Addicted Brain Addicted Brain Control Control CG STOP Saliency NAc Drive OFC Saliency Drive GO Memory Amygdala Memory Adapted from: Volkow et al., J Clin Invest 111(1):1-11, 2.
Neurobiological Advances in Addiction Science: Implications For Prevention and Treatment Nora D. Volkow, M.D. Director
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