National Institute on Drug AbuseBringing the full power of science to bear on Drug Abuse and AddictionNora D. Volkow, M.D.DirectorNational Institute on Drug Abuse

Nora D. Volkow, M.D.Director

National Institute on Drug Abuse

ationalnstitute

on rug buse

… Bringing the full power of science to bear on

Drug Abuse & Addiction

Addiction Involves Multiple FactorsADDICTION INVOLVES MULTIPLE FACTORS

Addiction

DRUG

Brain Mechanisms

Biology/GenesJo

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Environment

National Institute on Drug Abuse PortfolioFY 2008 Actual

Epidemiology, Services & Prevention Research -- 24%

Basic & Clinical Neuroscience & Behavioral Research -- 47%

Pharmacotherapies & Medical Consequences -- 11%

Intramural Research -- 8%

Clinical Trials Network -- 4%

RM&S -- 6%

National Institute on Drug Abuse Portfolio FY 2008 Actual

Priority Areas for NIDAPriority Areas for NIDA

(New Targets & New Strategies)

HIV/AIDS Research

(Children & Adolescents)genetics/epigeneticsdevelopmentenvironmentco-morbidity

Treatment Interventions

Prevention Research

Addiction Is A Developmental DiseaseStarts in Adolescence and Childhood

NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

AgeAge at tobacco, at alcohol and at cannabis dependence as per DSM IV

0.0%

0.2%

0.4%

0.6%

0.8%

1.0%

1.2%

1.4%

1.6%

1.8%

5 10 15 20 25 30 35 40 45 50 55 60 65

% in

eac

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who

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THCALCOHOL

TOBACCO

ADDICTION IS A DEVELOPMENTAL DISEASEstarts in adolescence and childhood

Brain areas where volumes are smaller in adolescents than young adults

Sowell, E.R. et al., Nature Neuroscience, 2, 859-861, 1999.

SubcorticalFrontalParietalOccipitalTemporal

Percentage of U.S. 12th Grade Students Reporting Past Month Use of Cigarettes and Marijuana, 1975 to 2008

Percentage of U.S. 12th Grade Students Reporting Past Month Use of

Cigarettes and Marijuana, 1975 to 2008

CESAR FAX January 19, 2009, Vol. 18, Issue 2.Adapted by CESAR from University of Michigan, “Trends in 30-Day Prevalence of Use of

Various Drugs in Grades 8, 10, and 12,”Monitoring the Future study, 2008.

Cigarettes

Marijuana

40%

30%

20%

10%

0%1978 1982 1986 1990 1994 1998 2002 2006

1976 1980 1984 1988 1992 1996 2000 2004 2008

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

Biological Psychiatry

…and with the risk of suchsmoking-related diseases aslung cancer and peripheralarterial disease

Convergent Results Support CHRNA5/A3/B4 Gene Cluster Association with Nicotine Dependence

Epigenetic Marks Are Altered by Repeated Exposure to Drugs of AbuseCocaine induces the transcription factor ΔFosB, which co-activates HAT leading to sustained acetylation of histones and activation of genes, such as Cdk5, involved in addiction

Cocaine induces the transcription factor • FosB, which co-activates HAT leading to sustained acetylation of histones and activation of genes, such as Cdk5, involved in addiction

Kumar et al Neuron 48: 303-314 2005

Epigenetic Marks Are Altered by Repeated Exposure to Drugs of Abuse

How Do Genes Influence Brain Development, Behavior and Disease?

How Do Genes Influence Brain Development,Behavior and Disease?

*Adapted from Hamer, Science, 2002; MAO A genotype studies from Caspi et al., Science, 2002.

BRAIN FUNCTION

Risk for Disease

Behavior*

Protein expressionNeurotransmissionCBFMetabolismElectrophysiology

Symptomsand

DISEASE

Medications for Relapse PreventionMedications for Relapse Prevention

Strengthen prefrontal-striatal communication

Executive function/Inhibitory control

Interfere with conditioned memories (craving)

Teach new memories

Counteract stress responsesthat lead to relapse

Interfere with drug’sreinforcing effects

Addicted Brain

Drive

Control

Saliency

Memory

GOSTOPDrive

Control

Memory

Non-Addicted Brain

Saliency

VaccinesEnzymatic degredationNaltrexoneDA D3 antagonistsCB1 antagonists

BiofeedbackModafinilBupropionStimulants

Antiepileptic GVGN-acetylcysteine

Cycloserine

CRF antagonistsOrexin antagonists

AdenosineA2 antagonistsDA D3 antagonists

Roadblock # 1: Lack of Pharmaceutical Industry Interest in Developing Medications to Treat Addiction;The Process of New Drug Development is Long…and Expensive

PRE-CLINICAL RESEARCH CLINICAL STUDIES NDA REVIEW POST-MARKETING

AVG: 18 MOS.IND

AVG: 5 YEARSNDA APPROVAL

DIS

CO

VE

RY

/SC

RE

EN

ING

SYNTHESISANDPURIFICATION

ANIMALTESTING

AVG: 24 MOS.

ADVERSEREACTION

SURVEILLANCEPRODUCT DEFECT

REPORTING

SURVEYS/SAMPLINGTESTING

POST APPROVALINSPECTIONS

SHORT-TERM

LONG-TERM

PHASE I

PHASE II

PHASE III PHASE IV

ACCELERATED APPROVAL

PARALLEL TRACK

TREATMENT USE

The Process of NEW DRUG DEVELOPMENTIs Long…and Expensive

ROADBLOCK #1: Lack of Pharmaceutical IndustryInterest in Developing Medications to Treat Addiction

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

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

Addiction Contributes to Many Serious Medical Consequences: Mental IllnessCancerInfectious Diseases (HIV/HCV)CardiacPulmonaryLearning DisordersObesityCerebrovascular (strokes)Trauma (accidents)

ADDICTION CONTRIBUTES TO MANY SERIOUS MEDICAL CONSEQUENCES

• Mental Illness• Cancer• Infectious Diseases

(HIV/HCV)• Cardiac• Pulmonary• Learning Disorders• Obesity• Cerebrovascular

(strokes)• Trauma

(accidents) Source: Fowler JS et al., PNAS. 2003;100(20):11600-5.

Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users

0

5

10

15

20

Current Injectors

Non-Injectors

HIV

Pre

vale

nce

13%CI 12-15%

12%

CI 9-16%

Drug Treatment Program(n=2121 2001-2004)

Respondent-Driven Sampling (n=448 2004)

0

5

10

15

2015%

CI 11-19%

17%CI 12-21%

Source: Des Jarlais et al AIDS, 21: 231-235, 2007.

Current Injectors

Non-Injectors

Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users

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 AbusedAny Illicit Drugs or Alcohol

But…Only 3.9 Million (17%) of These Individuals

Had Received Some Type ofTreatment In the Past Year

Source: 2007 NSDUH, National Findings, SAMHSA, OAS, 2008.

Self Help Group

Outpatient Rehab

Inpatient Rehab

Outpatient Mental Health Center

Hospital Inpatient

Private Doctor’sOffice

Emergency Room

Prison or Jail

Numbers in Millions0 .5 1.0 1.5 2.0 2.5

2.2

1.7

1.0

0.9

0.8

0.6

0.5

0.3

Location TX Received

ROADBLOCK #3: Although Treatments For Addiction Are Available, They Are Not

Being Widely Used By Those Who Need Them

Treatment Linkage & Days Used Heroin6 Months Post-release

Days Used Heroin

Treatment Linkage & Days Used Heroin6 Months Post-release

Source: Gordon, MS et al., Addiction 103:1333-1342, 2008.

C = Counseling Only C+T = Counseling & Treatment Referral C+M = Counseling & Methadone Started in Prison

11

85

35

57

64

46

80%

C C + T C + M

Days In Treatment

70%60%50%40%30%20%10%

0%

90%

Blending Research and Practice

National Drug Abuse TreatmentClinical Trials Network (CTN)

NIDA Criminal Justice Drug Abuse Treatment Studies (CJ-DATS)

Research Center

Research Centers & CJ Partner Sites

Blending Research and Practice

Oregon/Hawaii NodeOHSU

Pacific NorthwestNode

U. Washington

Pacific NodeUCLA

Texas NodeUT/S. Med Center

Florida NodeU. Miami

Appalachian Tri-State NodeWPIC/U of Pitt.

Ohio Valley NodeU. Cincinnati

Southern ConsortiumNode

MUSC

California/Arizona NodeUCSF/U. Arizona

Southwest NodeU. New Mexico

Northern NE NodeMcLean/Harvard

New England NodeYaleNew York Node

NYULong Island Node

NY State Psych. Inst.

Delaware Valley NodeU. Pennsylvania

Mid-Atlantic NodeJHU/MCV