The Impact of Research on the Care of Addicted Patients A Update Nora D. Volkow, M.D. Director National Institute on Drug Abuse
HISTORY - previous history - expectation - learning DRUGS BIOLOGY - genetics - circadian rhythms - disease states - gender BRAIN MECHANISMS ADDICTION ENVIRONMENT - social interactions - stress - conditioned stimuli
Priority Areas for NIDA Prevention Research (Children and Adolescents) genetics development environment co-morbidity Treatment Interventions (New Targets) HIV/AIDS Research Training Researchers
Recent Studies Have Shown that Maturation of the Brain s Gray Matter Moves from Back to Front This Means That Cognitive Processing and Other Executive Functions Develop Later than Spatial, Sensory and Language Functions Differences in gray-matter density between: 16 year olds (adolescents) and 23-30 year olds (young adults) Frontal Lobe Subcortical Region Likely reflect myelination differences Source: Sowell, E.R. et al., Nature Neuroscience, 2(10), pp. 859-861, 1999
What are Consequences of Drugs During Pregnancy? Smoking Low Birth Weight Conduct Disorder in Childhood and Adolescence Early Experimentation with Tobacco ADHD IQ What are the Neurobiological effects of drug exposure during brain development????
Mapping Drug Risk Factors in a Community Poor Family Support Drug availability No students in this area. Insufficient number of students in this area. Neighborhood #2 Poverty Crime Neighborhood #3 Neighborhood #1 John A. Pollard, Ph.D. Developmental Research and Programs What are the neurobiological factors that mediate social stressors as a risk factor for drug abuse?
Dopamine D2 Receptors are Lower in Addiction DA D2 Receptor Availability DA DA Cocaine Alcohol DA DA DA DA DA DA DA DA DA DA Reward Circuits Non-Drug Abuser DA DA DA DA DA DA Heroin control addicted Reward Circuits Drug Abuser
Individually Housed Group Housed 50 Dominant Subordinate Reinforcers (per session) 40 Dominant 30 20 * * 10 Subordinate 0 S.003.01.03.1 Cocaine (mg/kg/injection) Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002.
Comorbidities: Smoking Epidemiology normal population: 23% alcoholism: 90%+ other addictions: 90%+ schizophrenia: 85% depression: 80%
Priority Areas for NIDA Prevention Research (Children and Adolescents) genetics development environment co-morbidity Treatment Interventions: New Targets New Strategies HIV/AIDS Research Training Researchers
New Targets CB1 KO mice have decreased responses to multiple drugs of abuse Smokers who are poor nicotine metabolizers smoke less Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress Medication CB1 Antagonists Inhibitors of metabolizing enzymes CRF Antagonists
New Strategies Neuroscience Research has shown that the Human Adult Brain is Susceptible to Plastic Changes in Response to Environmental Stimulation
Source: Maguire, E.A. et al., PNAS, 97(8), pp. 4398-4403, 2000. Posterior Hippocampi of London Taxi Drivers Were Significantly Larger Than Those of Controls Positive Correlation Between Gray Matter Volume and Time As A Taxi Driver
The Plasticity of the Brain lhas Implications for The Design of Behavioral Interventions to Help Remediate Brain Changes Induced by Chronic Exposure to Drugs of Abuse control cocaine abuser
Treatment Strategies Clinical Practice and the Community As we strengthen our knowledge on treatment of addiction it becomes increasing urgent to expand our research on strategies to optimize their translation into clinical practice and the community
The Majority of People Who Need Treatment for Drug Abuse Problems Don t Receive It! % Not Treated 100 90 80 70 60 50 40 30 20 10 0 68% 62% 61% 57% 54% 63% 63% 57% 1991 1992 1993 1994 1995 1996 1997 1998 Source: OAS, SAMHSA. Unpublished Data from the National Household Survey on Drug Abuse and Uniform Facility Data Set (1991-1998) in National Drug Control Strategy 2000 Annual Report Table 39, p. 140.
Community Bedside Bench
TRANSLATIONAL BOTTLENECK Source: Hyman, S.E. and Fenton, W.S. Science, 299, pp. 350-351, January 17, 2003.
Percentage of Recommended Care Received Senile cataract Breast cancer Prenatal care Low back pain CAD Hypertension Congestive heart failure Cerebrovascular disease COPD Depression Orthopedic conditions Osteoarthritis Colorectal cancer Asthma Benign prostatic hyperplasia Hyperlipidemia Diabetes mellitus Headache UTI Community-acquired pneumonia STDs Dyspepsia and peptic ulcer disease Atrial fibrillation Hip fracture Alcohol dependence 0 20 40 60 80 100 Source: McGlynn, E.A., NEJM, 348, pp. 2635-2645, June 26, 2003
Pacific Northwest Node University of Washington National Drug Abuse Treatment Clinical Trials Network Pacific Node UCLA Northwest Node Oregon Health Sciences University Rocky Mountain Node University of Colorado Health Sciences Center California/Arizona Node University of California University of Arizona Northern New England Node Harvard University New Great Lakes Regional Node England Node Yale University Wayne State University Long Island Regional Node NY State Psych Inst NYC East Side Node NY University/NY VA Med Ctr Delaware Valley Node University of PA Ohio Valley Node University of Cincinnati Mid-Atlantic Node Johns Hopkins University North Carolina Node Medical College of VA Duke University New Mexico Node Univcersity of New Mexico Southeastern Node Medical University of South Carolina CTN Sites Florida Node University of Miami
DHHS NIH SAMHSA NIDA Translate Research Findings Into Relevant Clinical Practice
Priority Areas for NIDA Prevention Research (Children and Adolescents) genetics development environment co-morbidity Treatment Interventions (New Targets) HIV/AIDS Research Training Researchers
Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease
PercentofCases Proportions of AIDS Cases by Exposure and Year of Diagnosis, USA 70 60 Men who have sex with men (MSM) % of Cases 50 40 30 20 Injection drug use (IDU) Heterosexual contact 10 0 1986 1988 1990 1992 1994 1996 Year of Diagnosis Source: Centers for Disease Control and Prevention (CDC) 1998 2000
Effects of Alcohol (1g/kg) on Brain Glucose Metabolism sober intoxicated (0.1 mg%)
Acceleration of HIV Degeneration of Dopamine Cells With Cocaine Seronegative HIV HIV + Drug
Priority Areas for NIDA Prevention Research (Children and Adolescents) genetics development environment co-morbidity Treatment Interventions (New Targets) HIV/AIDS Research Training Researchers
NIDA S Research Training/ Mentored Career Awards F30 - Predoctoral Individual Fellowship for M.D./Ph.D. F31 - Predoctoral Individual Fellowship F32 - Postdoctoral Individual Fellowship 600 500 T32 - Institutional Research Training Grant T35 - Short-Term Research Training Grant # of Awards 400 300 200 100 K01 - Mentored Research Scientist Development Award K08 - Mentored Clinical Scientist Development Award K12 - Mentored Clinical Scientist Development Program Award K23 - Mentored Patient-Oriented Research Career Development Award K22 NIDA Scholars Program K25 - Mentored Quantitative Research Career Development Award 0 86 87 88 89 90 91 92 93 94 95 96 97 98 99 0 1 2 3* Fiscal Year *Estimate Individual Institutional
Systems and Translational Research Approaches in Addiction DRUGS OF ABUSE social behavior neuronal circuits protein expression genome