Bringing the full power of science to bear on Drug Abuse & Addiction

Transcription

1 ational nstitute on rug buse Bringing the full power of science to bear on Drug Abuse & Addiction Nora D. Volkow, M.D. Director National Institute on Drug Abuse

2 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 Biology/Genes Environment DRUG Brain Mechanisms Addiction

3 National Institute on Drug Abuse Portfolio Basic & Clinical Neuroscience & Behavioral Research -- 47% Epidemiology, Services & Prevention Research -- 24% Pharmacotherapies & Medical Consequences -- 11% Clinical Trials Network -- 4% Intramural Research -- 8% RM&S -- 6%

4 Priority Areas for NIDA Prevention Research (Children & Adolescents) genetics/epigenetics development environment co-morbidity Treatment Interventions (New Targets & New Strategies) HIV/AIDS Research

5 % in each age group who develop ADDICTION IS A DEVELOPMENTAL DISEASE starts in adolescence and childhood first time dependence 1.8% 1.6% 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% TOBACCO THC ALCOHOL Subcortical Frontal Parietal Occipital Temporal Brain areas where volumes are smaller in adolescents than young adults Sowell, E.R. et al., Nature Neuroscience, 2, , % 0.0% Age Age at tobacco, at alcohol and at cannabis dependence as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

6 Convergent Results Support CHRNA5/A3/B4 Gene Cluster Association with Nicotine Dependence Biological Psychiatry and with the risk of such smoking-related diseases as lung cancer and peripheral arterial disease

7 How Do Genes and Epigenetic Modifications Influence Brain Development, Behavior and Disease? Risk for Disease Behavior* BRAIN FUNCTION Protein expression Neurotransmission CBF Metabolism Electrophysiology Symptoms and DISEASE *Adapted from Hamer, Science, 2002; MAO A genotype studies from Caspi et al., Science, 2002.

8 Medications for Relapse Prevention Addicted Brain Control Interfere with drug s reinforcing effects Executive function/ Inhibitory control Vaccines Enzymatic degredation Naltrexone DA D3 antagonists CB 1 antagonists Biofeedback Modafinil Bupropion Stimulants Saliency Drive GO Strengthen prefrontalstriatal communication Adenosine A2 antagonists DA D3 antagonists Memory Interfere with conditioned memories (craving) Teach new memories Antiepileptic GVG N-acetylcysteine Cycloserine Counteract stress responses that lead to relapse CRF antagonists Orexin antagonists

9 Medications for Relapse Prevention Non-Addicted Addicted Brain Brain Control Control Interfere with drug s reinforcing effects Executive function/ Inhibitory control Vaccines Enzymatic degredation Naltrexone DA D3 antagonists CB 1 antagonists Biofeedback Modafinil Bupropion Stimulants Saliency Drive Drive STOP GO Strengthen prefrontalstriatal communication Adenosine A2 antagonists DA D3 antagonists Memory Memory Interfere with conditioned memories (craving) Teach new memories Antiepileptic GVG N-acetylcysteine Cycloserine Counteract stress responses that lead to relapse CRF antagonists Orexin antagonists

10 DISCOVERY/SCREENING ROADBLOCK #1: Lack of Pharmaceutical Industry Interest in Developing Medications to Treat Addiction PRE-CLINICAL RESEARCH CLINICAL STUDIES NDA REVIEW POST-MARKETING SYNTHESIS AND PURIFICATION PHASE I PHASE II PHASE III ADVERSE REACTION SURVEILLANCE PRODUCT DEFECT REPORTING PHASE IV ANIMAL TESTING SHORT-TERM LONG-TERM ACCELERATED APPROVAL TREATMENT USE PARALLEL TRACK SURVEYS/ SAMPLING TESTING POST APPROVAL INSPECTIONS AVG: 18 MOS. IND AVG: 5 YEARS NDA AVG: 24 MOS. APPROVAL The Process of NEW DRUG DEVELOPMENT Is Long and Expensive

11 ROADBLOCK #2: Erosion of the Medical Community s Involvement in Preventing and Treating Drug Abuse and Addiction Primary Care Physicians Are Often Reluctant To Treat Substance Abuse or Fail to Link This With Their Patients Other Medical Conditions

12 ROADBLOCK #3: Although Treatments For Addiction Are Available, They Are Not Being Widely Used By Those Who Need Them In 2007 An Estimated 22.3 Million Americans Were Dependent On or Abused Any Illicit Drugs or Alcohol But Only 3.9 Million (17%) of These Individuals Had Received Some Type of Treatment In the Past Year Self Help Group Outpatient Rehab Inpatient Rehab Outpatient Mental Health Center Hospital Inpatient Private Doctor s Office Emergency Room Prison or Jail Location TX Received Source: 2007 NSDUH, National Findings, SAMHSA, OAS, Numbers in Millions

13 Blending Research and Practice National Drug Abuse Treatment Clinical Trials Network (CTN) NIDA Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) Research Centers & CJ Partner Sites Oregon/Hawaii Node OHSU California/Arizona Node UCSF/U. Arizona Pacific Northwest Node U. Washington Ohio Valley Node U. Cincinnati Appalachian New York Node Tri-State Node NYU WPIC/U of Pitt. Northern NE Node McLean/Harvard New England Node Yale Long Island Node NY State Psych. Inst. Delaware Valley Node U. Pennsylvania Mid-Atlantic Node JHU/MCV Pacific Node UCLA Southwest Node U. New Mexico Southern Consortium Node MUSC Texas Node UT/S. Med Center Florida Node U. Miami Research Center

14 Priority Areas Prevention Genetics Environment Development Neurobiology Interventions Policy Treatment Neural mechanisms Medications Development Brain circuitry Implementation Consequences HIV/AIDS Fetal Exposure

15 2009 Dr. Benjamin Chen Mt. Sinai School of Medicine Visualizing early events of parenteral HIV transmission (cellcell vs. free virus) 2009 Dr. Dana Gabuzda Dana Farber Cancer Institute & Harvard Medical School Control of T cell restoration in HIVinfected IV drug abusers 2010 Dr. Eric Verdin Gladstone Institutes New methods to detect and model HIV latency 2009 Dr. Jonathan Karn Case Western Reserve University Developing strategies for long-term HIV suppression 2011 Dr. David Ho Aaron Diamond AIDS Research `Center Develop a novel HIV therapy that could be administered monthly 2009 Dr. Rafick-Pierre Sekaly Vaccine & Gene Therapy Institute, FL Novel pathways for purging the HIV reservoir 2008 Dr. Ileana Cristea Princeton University Quantifying HIV host interactome and regulation of gene expression 2008 Dr. Jerome Groopman Beth Israel Medical Center & Harvard Medical School Blocking HIV transmission at the immune synapse 2008 Dr. Julio Montaner University of British Columbia HIV treatment as prevention in drug using populations