Science of Drug Addiction “In the past 30 years,

advances in science have revolutionized our understanding of drug abuse and addiction. We now know that drug addiction is a complex brain disease. It involves multiple factors and usually starts in adolescence.”Nora D. Volkow, M.D.

Director, National Institute on Drug Abuse

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Blockade in these regions blocks relapse or reinstatement

Drug Seeking Behavior – Motor Subcircuit

glutamate

Reward – Limbic Subcircuit

dopamine

Blockade in theseregions blocksinitiation of druguse, but notrelapse

Different Brain Circuitry Involved inDrug Reward and Drug Persistence Behavior

Different Brain Circuitry Involved inDrug Reward and Drug Persistence Behavior

Source: Adapted from McFarland, K. and Kalivas, P.W. Journal of Neuroscience, 21(21), pp. 8655-8663, November 1, 2001.Source: Adapted from McFarland, K. and Kalivas, P.W. Journal of Neuroscience, 21(21), pp. 8655-8663, November 1, 2001.

NIDA’s Neuroscience Program

Defining the Problems...Defining the Problems...

Developing the Tools...Developing the Tools...

Genetics Research at NIDAGenetics Research at NIDA

Genetics Research at NIDAGenetics Research at NIDA

40-50% of the vulnerability to addiction is genetic

Genetic Variation Predicts Naltrexone Treatment Response for Alcohol Dependence

Genetic Variation Predicts Naltrexone Treatment Response for Alcohol Dependence

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Naltrexone/Asp40 Allele (A/G, G/G) (n=23)

Naltrexone/Asn40 Allele (A/A) (n=48)

Placebo/Asn40 Allele (A/A) (n=41)

Placebo/Asp40 Allele (A/G, G/G) (n=18)

Oslin, Berrettini, Volpicelli, Kranzler, O’Brien, et al., 2003Oslin, Berrettini, Volpicelli, Kranzler, O’Brien, et al., 2003

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Amphetamine and the Hallucinogen DOI Amphetamine and the Hallucinogen DOI Produce Different Protein Profiles in Produce Different Protein Profiles in

BrainBrain

Amphetamine and the Hallucinogen DOI Amphetamine and the Hallucinogen DOI Produce Different Protein Profiles in Produce Different Protein Profiles in

BrainBrain

High-Throughput Genome-Wide Scan High-Throughput Genome-Wide Scan for Addiction Locifor Addiction Loci

High-Throughput Genome-Wide Scan High-Throughput Genome-Wide Scan for Addiction Locifor Addiction Loci

• NIDA plans to work with Perlegen Sciences to utilize their resource of 1.5 million single nucleotide polymorphisms in a whole genome scan to identify drug addiction loci

• Three groups from the NIDA Genetics Consortium competed for access to the Perlegen resource -- A group studying nicotine genetics, headed by Dr. Laura Bierut, has been granted access

• NIDA plans to work with Perlegen Sciences to utilize their resource of 1.5 million single nucleotide polymorphisms in a whole genome scan to identify drug addiction loci

• Three groups from the NIDA Genetics Consortium competed for access to the Perlegen resource -- A group studying nicotine genetics, headed by Dr. Laura Bierut, has been granted access

40-50% of the vulnerability to addiction is genetic

Adolescent Brain DevelopmentAdolescent Brain Development

ADDICTION IS A DEVELOPMENTAL DISEASE It starts in adolescence and childhood

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

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Age at cannabis use disorder as per DSM IV

Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179

Brain Maturation from Ages 5 to 20

Imaging and Other Innovative Technologies

Imaging and Other Innovative Technologies

Partial Recovery of Brain Metabolism and Function in Methamphetamine Abusers After

Protracted Abstinence

Partial Recovery of Brain Metabolism and Function in Methamphetamine Abusers After

Protracted Abstinence

Short AbstinenceShort Abstinence

Protracted AbstinenceProtracted Abstinence% Metabolic Change

Improved memory correlates with thalamic recovery

Improved memory correlates with thalamic recovery

Adapted from Wang, Volkow, et al, (2004) American Journal of Psychiatry 161: 242-8 (scans unpublished)

Genetics Mechanisms Treatments Genetics Mechanisms Treatments

We Are Using Science toDevelop Even Better Treatment

We Are Using Science toDevelop Even Better Treatment

NIDA Has Numerous Mechanisms To Fund Innovative

Drug Abuse Research

NIDA Has Numerous Mechanisms To Fund Innovative

Drug Abuse Research

Some Recent RFAs and PAsSome Recent RFAs and PAs RFA-DA-05-003RFA-DA-05-003 Developmental Centers for Translational Developmental Centers for Translational

Research on the Clinical Neurobiology of Drug AddictionResearch on the Clinical Neurobiology of Drug Addiction

PA-04-152PA-04-152 MDMA: Research Areas Needing More Interest MDMA: Research Areas Needing More Interest

PA-04-110PA-04-110 Prescription Drug Abuse Prescription Drug Abuse

PA-03-175PA-03-175 Fine Mapping Genes and Gene Variants for Drug Fine Mapping Genes and Gene Variants for Drug Addiction SusceptibilityAddiction Susceptibility

PA-03-155PA-03-155 Molecular Genetics of Drug Addiction Vulnerability Molecular Genetics of Drug Addiction Vulnerability

PAR-03-146PAR-03-146 (B/START) Behavioral Science Track Award for (B/START) Behavioral Science Track Award for Rapid TransitionRapid Transition

PAR-03-017PAR-03-017 Cutting-Edge Basic Research Awards (CEBRA) Cutting-Edge Basic Research Awards (CEBRA)

Find out more at: Find out more at: http://www.drugabuse.gov/funding/resfundslist.htmlhttp://www.drugabuse.gov/funding/resfundslist.html

NIDA CEBRA PROGRAMNIDA CEBRA PROGRAM

Foster highly innovative, novel or conceptually creative research that advances our understanding of drug abuse and addiction

Support research that is high-risk and potentially high-impact and that is underrepresented or not included in NIDA's current portfolio

PURPOSE

Micro-optical probesMicro-optical probes

CEBRA: Two-photon endoscopyCEBRA: Two-photon endoscopy(Mark Schnitzer)(Mark Schnitzer)

NIH ROADMAPNIH ROADMAPNIH ROADMAPNIH ROADMAP

• Building Blocks, Biological Pathways and Networks

• Molecular Library and Imaging

• Structural Biology• Nanomedicine• Bioinformatics and

Computational Biology

NEW PATHWAYS TO DISCOVERY

To accelerate the discovery and translation of biomedical research into new and effective prevention and treatment strategies.

RESEARCH TEAMS OF THE FUTURE• High-Risk Research• Interdisciplinary Research

RE-ENGINEERING THE CLINICAL RESEARCH ENTERPRISE

• Public-Private Partnerships

Current and Future Roadmap Funding OpportunitiesCurrent and Future Roadmap Funding Opportunities NEW PATHWAYS TO DISCOVERYMolecular Libraries and Imaging• Novel Preclinical Tools for Predictive ADME-

Toxicology • Cheminformatics Research Centers • Assay Technology Development (Re-

issuance)

• Pilot Scale Libraries for High Throughput Screening

• New Methodologies for Natural Products Chemistry

Building Blocks, Biological Pathways • National Technology Centers for Networks & Pathways (Re-issuance)Bioinformatics and Computational Biology• National Centers for Biomedical Computing (Re-issuance)Structural Biology• Membrane Protein Production and Structure DeterminationNanomedicine: Nanomedicine Development Centers

Neurosciences

Blueprint

Neurosciences

Blueprint

Sunday, October 24, 1:00 p.m.–3:00 p.m.Sunday, October 24, 1:00 p.m.–3:00 p.m.

Convention Center, Room 3Convention Center, Room 3

•Funding Opportunities:Funding Opportunities: http://www.drugabuse.gov/funding/resfundslist.html

•Training Opportunities:Training Opportunities: www.drugabuse.gov/researchtraining/traininghome.html

•Roadmap activities:Roadmap activities: http://www.drugabuse.gov/about/roadmap/index.html

www.drugabuse.govwww.drugabuse.gov