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National Institute on Drug Abuse Bringing the full power of science to bear on drug abuse and addiction Nora D. Volkow, M.D. Director National Institute on Drug Abuse Nora D. Volkow, M.D. Director ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function Decreased Brain Metabolism in Drug Abuse Patient High Control Cocaine Abuser Decreased Heart Metabolism in Heart Disease Patient Low Healthy Heart Diseased Heart Sources: From the laboratories of Drs. N. Volkow and H. Schelbert % in each age group who develop firsttime cannabis use disorder ADDICTION IS A DEVELOPMENTAL DISEASE starts in adolescence and childhood 1.6% Prefrontal Cortex 1.4% 1.2% 1.0% 0.8% Amygdala 0.6% Brain areas where volumes are smaller in adolescents than young adults 0.4% 0.2% Sowell, E.R. et al., Nature Neuroscience, 2, 859-861, 1999 0.0% 5 10 15 18 25 30 35 40 45 50 55 60 65 70 Age Age at cannabis use disorder as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003 % of Basal Release Drugs and Natural Rewards ACTIVATE Dopamine in Reward Regions frontal cortex nucleus accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 AMPHETAMINE 0 VTA/SN 1 2 3 4 Time After Amphetamine FOOD % of Basal Release 200 Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction 5 hr 150 100 50 0 Empty Box Feeding 0 60 120 180 Time (min) Di Chiara et al. Repeated Drug Use Changes the Brain Weakens the Brain Dopamine System Control Cocaine Abuser TYROSINE TYROSINE TYROSINE DOPA DOPA DOPA DA DA DA DA DA DA DA DA DA DA DA DA DA COCAINE DA DA DA DA DA DA DA DA DA DA DA DA PLEASURE REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES LEVELS OF DOPAMINE D2 RECEPTORS Dopamine D2 Receptors are Lower in Addiction Normal Controls Cocaine Abusers 4.5 4 DA D2 Receptors (Ratio Index) Cocaine 3.5 3 2.5 2 Meth 1.5 15 20 25 30 35 40 45 50 3.2` 3 2.8 Bmax/Kd Alcohol 2.6 2.4 2.2 2 1.8 1.6 Heroin 20 control addicted 25 30 35 40 45 Volkow et al., Neuro Learn Mem 2002. 50 50 40 2nd D2R Vector 60 p < 0.0005 p < 0.0005 p < 0.005 30 20 p < 0.005 p < 0.10 10 0 0 4 6 8 10 24 0 Null Vector Percent Change in D2R Overexpression of DA D2 receptors reduces alcohol self-administration 1st D2R Vector Effects of Tx with an Adenovirus Carrying a DA D2 Receptor Gene into NAc in DA D2 Receptors -20 -40 p < 0.01 p < 0.01 -60 p < 0.001 -80 -100 p < 0.001 p < 0.001 0 Thanos, PK et al., J Neurochem, 78, pp. 1094-1103, 2001. 4 6 8 10 Time (days) 24 Low Levels of Striatal D2 Receptors Are Associated with Impaired Activity in Frontal Regions 65 60 50 45 Control umol/100gr/min 40 OFC addicted Brain glucose metabolism 55 35 30 1.8 90 2 2. 2 2.4 2. 6 2.8 3 3.2 3. 4 80 70 60 40 35 30 30 2.9 3 3.1 3.2 3.3 3.4 3.5 3.6 36 34 32 30 28 26 24 2 2 .5 3 3 .5 4 Volkow et al., PNAS D2R 2011 VS 108(37): 15037-42 4 50 38 22 1 .5 Methamphetamine Abusers Controls Metabolism Prefrontal (micromol/100g/min) 45 40 Metabolism OFC (micromol/100g/min) control 50 50 25 1 .5 Cocaine Abuser 45 40 0 35 Controls 30 2 2 .5 3 3 .5 D2 Receptors (BP ) D2R VS ND 4 1 .5 Alcoholics 2 2 .5 3 3 .5 VS DA D2D2R receptors (Bmax/Kd) 4 ADDICTION CAN BE TREATED Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 ml/gm Normal Control METH Abuser (1 month detox) METH Abuser (14 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001. Opportunities with Health Care Reform to Expand Involvement of the Health Care System in Treatment of SUD In 2012 An Estimated 22.2 Million Americans 12 or Older Were Dependent On Any Illicit Drugs or Alcohol But …Only 4 Million (18%) of These Individuals Had Received Some Type of Tx In the Past Year and Few involved Health Care Systems Location TX Received Self Help Group 2.1 Outpatient Rehab 1.5 Inpatient Rehab 1.0 Outpatient Mental Health Center 1.0 0.8 Hospital Inpatient 0.7 Doctor’s Office 0.6 Emergency Room Prison or Jail 0.4 0 .5 1.0 1.5 2.0 Numbers in Millions Source: 2012 NSDUH, National Findings, SAMHSA, OAS, 2013. 2.5 Evaluation of A Hypothetical Treatment Symptom Severity 10 HYPERTENSION 9 8 7 6 5 4 3 2 1 0 Pre During Symptom Severity 10 During During Post ADDICTION 9 8 7 Just Like Hypertension, Addiction Is A Chronic Disease That Requires Continued Care 6 5 4 3 2 1 0 Pre During During During Stage of Treatment Post Source: McLellan, AT, Addiction 97, 249-252, 2002. ADDICTION TREATMENT Addiction is a chronic disease and requires continued care No single treatment is appropriate for everyone Medications are an important element of treatment for many patients, Drug use during treatment must be monitored continuously, as lapses during treatment occur and need to be addressed Attends to multiple needs of the individual, including co-morbid mental illness and infectious diseases (HIV, HCV, HBV, TB) Treatment does not need to be voluntary to be effective Medications for Opioid Addiction agonist antagonist no effect effect an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect an antagonist drug is close enough in shape to bind to the receptor but not close enough to produce an effect. It also takes up receptor space and so prevents the endogenous ligand from binding Opioid Effect Full Agonist (Methadone) Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013. Partial Agonist (Buprenorphine) Antagonist (Naloxone) Log Dose Opioid Agonist Treatments Decreased Heroin Overdose Deaths Heroin overdoses Buprenorphine patients Methadone patients Schwartz RP et al., Am J Public Health 2013;1 03: 917-922. Patients Treated, No. Overdose Deaths, No. Baltimore, Maryland, 1995-2009 Methadone Maintenance Therapy Improves HIV Outcomes in IDU Antiretroviral Adherence and HIV Treatment Outcomes Among HIV/HCV Co-Infected IDU: Role of Methadone Adjusted Odds Ratio Methadone Maintenance Therapy Promotes Initiation Of Antiretroviral Therapy IDU Uhlmann S et al., Addiction 2010; 105(5):907-913. Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194. Implementation research Lack of uptake of medication-assisted treatment TOO FEW ARE TREATED Addiction Specialty Programs Offering Services As % of all programs surveyed (N=345) Within adopting programs, % of eligible patients receiving Rx Methadone 7.8 41.3 Buprenorphine 20.9 37.3 Tablet naltrexone 22.0 10.9 Opioid Tx Meds: Knudsen et al, 2011, J Addict Med; 5:21-27. ED-initiated Buprenorphine Increased Engagement In Addiction Treatment, Reduced Self-reported Illicit Opioid Use, & Decreased Use Of Inpatient Addiction Treatment Services % engaged in treatment on the 30th day after randomization D’Onofrio JAMA. 2015. 100 90 80 70 60 78% 5.4 5.6 5.4 50 40 2.3 30 20 0.9 37% 45% 2.4 10 0 Buprenorphine Referral Brief Intervention Number of days of illicit opiate use per week Medications Are An Important Part Of Treatment For Many Drug Abusing Offenders Methadone Maintenance For Prisoners: Results At 12 Months Post-release 80% 70% 60% 50% 40% 30% 20% 10% 0% -10% 66% 49% 37% 25% 17% 0% C In Treatment for one year at 12 months post-release Opiate + Urine Test at 12 months post release C+T C+M C = Counseling Only; C+T = Counseling & Transfer C+M = Counseling & Methadone Kinlock T, et al. J Subst Abuse Treatment 2009. Challenge: How to Integrate Drug Abuse & Addiction Screening, Prevention & Treatment into the Healthcare System Interventions Tailored to Severity In Treatment ~ 2,300,000 Addiction ~ 23,000,000 “Harmful – 40,000,000 Use” Little or No Use McLellan and Woodworth Journal of Substance Abuse Treatment, Volume 46, Issue 5, 2014, 541 - 545 Integration of Substance Use Disorders Into Healthcare System 1. SUDs are too omnipresent, dangerous & expensive in healthcare to be ignored 2. Market forces will accelerate integration • 2008 Parity Law providing for coverage of SUD at level of other medical diseases • 2010 Healthcare reform provides insurance to individuals with SUD that in the past would have not had access to healthcare 3.Mainstream healthcare needs to prepare for this • Integrate with specialty service Resources for Medical Students, Resident Physicians & Faculty • NIDA CoEs established in 2007 to help fill gaps in medical education curricula related to both illicit drugs and Rx drug abuse • Medical schools at CoEs have developed a diverse portfolio of innovative curriculum resources about how to identify and treat patients struggling with SUD Addicted Brain Non-Addicted Brain Control Control CG STOP Saliency NAc Drive OFC Memory Amygdala Adapted from: Volkow et al., J Clin Invest 111(10):1444-1451, 2003. Saliency Drive GO Memory