2004 nida topics

8/4/2019 2004 NIDA Topics

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NATIONAL INSTITUTE ON DRUG ABUSE(NIDA)

The mission of the NlDA is to lead the

nation in bringing the power of scienceto bear on drug abuse and addiction,

through support and conduct of researchacross a broad range of disciplines andby ensuring rapid and effective

dissemination and use of research results

to improve prevention, treatment, andpolicy. For additional information about

areas of interest to the NIDA, please

visit our home page at

http://www.nida.nih.gov/.

Phase II Competing Continuation Awards

(See http://grants.nih.gov/grants/guide/pa-files/PA-

03-154.html.)

NIDA will accept competingcontinuation Phase II SBIR/STTR grant

applications from Phase II SBIR/STTR

awardees to continue the process ofdeveloping products that require

approval of a Federal regulatory agency.

Such products include, but are notlimited to: medical implants, drugs,

vaccines, and new treatment or

diagnostic tools that require FDAapproval. This continuation grant should

allow small businesses to get to a stage

where interest and investment by third

parties is more likely.Please contact Dr. Cathrine Sasek

(contact information provided below)

before beginning the process of puttingan application together. Prospective

applicants are strongly encouraged to

contact NIH staff prior to submission of

a type 2 competing continuationapplication. Prospective applicants are

strongly encouraged to submit to the

program contact a letter of intent thatincludes the following information:

Descriptive title of the proposed

research

Name, address, and telephonenumber of the Principal Investigator

Names of other key personnel

Participating institutions

PA, RFA or Solicitation Number

(e.g., PA-03-154; PHS 2004-2)

Although a letter of intent is not

required, is not binding, and does not

enter into the review of a subsequentapplication, the information that it

contains allows NIH staff to estimate the

potential review workload and plan thereview. It is expected that only a portion

of NIDA SBIR/STTR Phase II awards

will be eligible for a competing

continuation grant.The following examples would make

appropriate topics for proposed SBIR or

STTR Phase II competing continuationprojects. These are meant for illustrative

purposes only and are not exclusive of

other appropriate activities.Research and development efforts can be

focused on medications for the treatment

of cocaine, methamphetamine, and other

stimulant abuse, as well as towardsopiate, cannabis, PCP and club drugs.

The medications under development

should be targeted towards attainment ofabstinence, maintenance, and/or relapse

prevention. Preclinical studies, including

pharmacology and toxicology,

beyond those conducted under theinitial SBIR Phase I and Phase IIgrants. The studies conducted

under the previous grants should besufficient to provide a sound

rationale for continued development

of the entity or entities.

Completion of studies as requiredby the FDA for an IND application.

Human laboratory clinical trials to

determine a medication's safetyprofile, metabolism, cardiovascular


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effects, interaction with drugs ofabuse, etc.

Clinical studies to assess the

efficacy of the medication underdevelopment.

Cathrine Sasek, Ph.D.

National Institute on Drug Abuse6001 Executive Boulevard

Room 5230, MSC 9591Bethesda, Maryland 20892-9591

(301) 443-6071, Fax: (301) 443-6277

Email: [email protected]

Division of Treatment Research andDevelopment

The NIDA Division of Treatment

Research and Development (DTR&D)

supports research aimed at thedevelopment and testing of

pharmacological and behavioral

treatments for drug abuse and addiction.This includes the identification,

evaluation, development, approvability,

and efficacy testing of new andimproved pharmacotherapeutic agents,

as well as the testing of marketed

medications, and of behavioral

treatments used alone or integrated with

medications. The DTR&D also advancesa human neuroscience research and

training program focused onunderstanding the neurobiological

substrates of drug abuse and addiction

processes.A. Chemistry and Pharmaceutics

Branch (CPB). The CPB supportsresearch in the design (includingmolecular modeling and structure-

activity relationship studies) andsynthesis of novel compounds,

formulation development, bioanalyticalmethods development, and

pharmacokinetics/ pharmacodynamicsaimed at the discovery anddevelopment of new medications for

treating drug addiction. Areas that maybe of interest to small businesses

include, but are not limited to researchrelated to the design and development

of new compounds and improved drugproducts (drug delivery) for thetreatment of drug addiction:

1. Synthesis of new chemical

compounds that would havepotential as treatment agents forthe medical management of

stimulant (e.g., cocaine,methamphetamine, or nicotine)

addiction. Consideration should begiven to the design of partial

agonists or pure antagonists thatdiminish the reinforcing effects ofstimulants, as well as full agonists

that could function to normalizephysiological activity following

discontinuation of stimulant use.

Compounds of interest include

those that are designed to affect

dopaminergic (i.e., D1 agonists, D3agonists and D3 antagonists)activity, CRF antagonists,

compounds affecting glutamateactivity, GABAergic activity, smallmolecule neuropeptide antagonists

and compounds acting throughother mechanisms for which

justification has been supplied.

2. The development of combinatorial

libraries for discovery of drugaddiction pharmacotherapies.

3. Synthesis of new chemicalcompounds with potential for the

treatment of opioid dependenceand/or craving. Compounds which

may prevent relapse to opiate usefollowing a period of drugabstinence are of special interest.

Kappa antagonists are of particularinterest.

Richard Kline, Ph.D.(301) 443-8293


4. Development of new approachesfor the administration of potentialaddiction treatment drugs with poor

bioavailability.

5. Development of controlled release

dosage forms for addictiontreatment medications in order to

maintain therapeutic drug levels forextended periods of time to


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alleviate compliance problemsassociated with addiction

treatment.

Moo Park, Ph.D.

(301) 443-5280

Email: [email protected]. Medications Discovery and

Toxicology Branch (MDTB). TheMDTB supports research on thedevelopment of preclinical behavioralmodels (e.g., of craving, drug-seeking

behavior, dependence, or relapse),biochemical assays, gene expressional

assays and electrophysiologicalmethods to identify and characterize

new medications to treat substanceabuse, as well as pharmacologicalscreening of novel compounds to

identify potential drug abusemedications. The Branch also supports

research on toxicity studies of potentialmedications for the treatment of

substance abuse, and interactions ofpotential treatment medications withabused substances. Areas that may be

of interest to small businesses include,but are not limited to development ofnew methods for discovery ofmedications useful in treating drugaddiction. Of special interest would bethe development of new animal models

of addiction, incorporating establisheddrug self-administration techniques thatshow increased relevance to the

clinical setting. Development ofrelevant biochemical or

electrophysiological screening methodsis also encouraged.

Jane B. Acri, Ph.D.(301) 443-8489

Email:[email protected]. Behavioral Treatment Development

Branch (BTDB). The BTDB supportsresearch on behavioral treatments and

combined behavioral andpharmacological treatments for drugabuse and dependence. Behavioral

treatments include psychotherapies,behavior therapies, family therapies,

group therapies, counseling strategies,rehabilitative techniques, brief

behavioral interventions, therapeuticcommunity treatments, and otherpsychosocial treatments. Research on

these treatments may be carried out inany setting, including both academic

and community or real-world settings.Areas that may be of interest to smallbusinesses include, but are not limited

to:

1. Behavioral Strategies for

Increasing Compliance in TakingTreatment Medication. Research todevelop and to evaluate strategiesto induce recovering addicts to take

medication for a prolonged time,especially antagonists such asNaltrexone; to induce HIV infected

drug users to comply with medicaltreatments (HAART) in drug abuse

treatment settings; or to adaptexisting behavioral strategies to

increase patient compliance andcooperation in long-term treatment

for drug abuse or for diseasesassociated with drug abuse suchas tuberculosis or hepatitis. An

important consideration should becost and practicality of use in

actual clinical practice or in anaftercare program. The product of

such research might be a manual,which describes the behavioralstrategy, and its implementation by

treatment staff or scientific dataregarding evaluation.

2. Integration of Behavioral Therapiesand Pharmacotherapies.Development and testing ofintegrated therapeutic approaches

for individuals who abuse variousdrugs, includingmethamphetamine, cocaine,

nicotine, and opioids; in additionthis may include individuals with

co-occurring substance abuse andmental disorders, since effective

treatment of both disorders maylead to improved treatment

outcomes. Integrated behavioraltherapies and pharmacotherapiesmay enhance the efficacy of both

types of therapeutic interventions.For instance, the maintenance and

detoxification of heroin addictscould perhaps be optimized by the

integration of distinctive behavioraltherapies devised specifically for


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opioid agonists, antagonists orpartial agonists determined by the

heterogeneity of the subgroup ofaddicts and the pharmacologicaldifferences of the medications.

Integration of medications andbehavioral therapies could possibly

enhance compliance with

medication regimens, increaseretention allowing pharmacologicaleffects to occur and preventrelapse to drug abuse and

addiction.

3. Behavioral Treatment Research forDrug Abuse and Addiction inPrimary Care. Recent research hasshown that physicians and otherclinicians often fail to recognize

drug abuse or addiction amongtheir primary care patients. In

addition, a significant number ofthese clinicians reported that theydid not know how to intervene with

their patients if drug abuse oraddiction was suspected. Drug

abuse related illnesses andmorbidity often occur in adults and

may have begun in adolescence.However, very little research hasbeen done to develop or test

behavioral treatment approachesor combined pharmacological and

behavioral treatments for drug

abuse and addiction in primarycare settings. The objectives of thisinitiative are to encourage researchon the development and testing of

innovative brief behavioraltreatment approaches, alone or in

combination with pharmacologicaltreatments that may be used in

various primary care patientpopulations and primary caresettings. Other goals of this

research initiative are to encourage

additional research on thedevelopment and evaluation ofculturally sensitive screening and

assessment instruments for use inprimary care; and to encourageresearch on the transportability of

efficacious behavioral treatments toprimary care settings, as well as

research on science-based trainingapproaches for changing primary

care clinicians' behaviors regardingtheir recognition and intervention

with drug abusing or addictedpatients. While motivationalenhancement approaches for some

drug abusing populations havebeen found to be effective, this

behavioral approach has not been

widely used in primary care.

4. Woman and Gender Differences inthe Provision of BehavioralTreatments, and HIV/AIDS RiskReduction Approaches. Developand evaluate specific behavioral

treatment approaches targetingdrug-addicted women. This may

include behavioral therapies, skillstraining techniques, counseling

strategies, and HIV and otherinfectious disease behavioral risk

reduction strategies. This may alsoinclude development and testing oftraining materials that specifically

address women and genderdifferences in drug addiction

treatment to promote effective useof research-based treatment

approaches. Training materialsmay involve treatment manuals,training videos, CD ROM or DVD

technologies, Internet or computerbased programs to manage

aspects of treatment

administration, or other innovativeeducational strategies for healthprofessionals using newtechnologies.

5. Transporting BehavioralTreatments to CommunityPractitioners. There is a need foreffective methods of transferring

behavioral therapies found to beeffective in clinical trials to clinical

practice. Cognitive-behavioraltherapy, operant behavioral

therapy, group therapy, and familytherapy are among the therapiesthat have been shown to be

efficacious in a highly controlledsetting and may be helpful

treatment approaches incommunity treatment programs as

well. However, communitypractitioners may have been


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trained using other approaches andmay not have been exposed to

these scientifically-basedapproaches. This is a call forproposals that examine

mechanisms to transfer effectiveresearch-based drug abuse

treatment information and skills-

based techniques to practitioners inthe community. This may involvethe development and testing ofinnovative training materials and

procedures to use in the training ofcommunity practitioners to skillfully

administer these treatments,including the development of highly

innovative technology transfer andcommunication approaches.Research testing the

transportability of empirically

supported therapies to thecommunity is an importantcomponent of the Behavioral

Therapies Development Program.

There is also a need for the

development of educationalmethods to train non-drug abuse

health care workers in relating todrug abusers; eliciting medicalhistories regarding past or present

drug abuse; recognition of thesigns and symptoms of drug

abuse; identification of those at

high-risk for HIV and other drugabuse related medical problemssuch as tuberculosis or hepatitis.Development and validation of a

drug abuse screening instrumentwhich can be administered by

primary health care providers, andtraining in administering such an

instrument.

6. Using Telemedicine to DisseminateDrug Addiction Research Findingsto Primary Health Care Providers.

Telemedicine programs are beingused in urban medical centers torapidly disseminate science-based

information on new medicaltreatments. In addition,

approximately one-third of the ruralhospitals are now using

telemedicine to improve patientcare. Health care professionals

need science-based information ondrug abuse prevention and

treatment. Research to developand evaluate telemedicineprograms to transport science-

based information on drugaddiction to the primary health care

community is encouraged.

7. Developing, Evaluating, andTransporting Culturally SensitiveBehavioral Therapies for Racialand Ethnic Minorities. Minoritypopulations are disproportionatelyaffected by the consequences of

drug abuse. Research to developand evaluate behavioral treatments

that are culturally sensitive andrelevant for diverse racial and

ethnic minority populations isencouraged. This may include

studies of behavioral treatments,alone or in combination withpharmacological treatment, or

studies of behavioral strategies forincreasing adherence to taking

medications. In the developmentand evaluation of the behavioral

treatment, attention needs to bedirected at examining medical,social, and cultural factors that may

influence adherence to thebehavioral treatment approach and

treatment outcome. Also, little is

known about the transportability ofefficacious behavioral treatmentsfor minority populations. Researchis needed on how to transport

science-based treatments tovarious racial/ethnic populations.

Dorynne Czechowicz, M.D.(301) 443-0107

Email: [email protected]. Behavioral Therapy Development.

Development of new or refinementof existing psychotherapies,

behavioral therapies, skills trainingtechniques or drug counseling

strategies for the treatment of drugabusers/addicts. Incorporation ofHIV risk reduction strategies as an

integral component in routinecounseling or other behavioral

interventions. This would includethe development of: therapy


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manuals, to define exactly what thetherapy is and how to administer it

optimally; competence andadherence scales, to evaluate theextent to which therapists and

counselors are actually providingthe therapy intended; process

measures, to measure various

aspects of the therapeuticinteraction; and measures of theintegrity and fidelity of the therapy.The following are of particular

interest:

a. Development of behavioral

therapies or components ofsuch therapies that are based

on developments and findingsfrom the basic behavioral or

cognitive sciences.

b. Discrete therapy componentsthat address specific problemscommon among drug addicted

individuals and that can beimplemented in conjunctionwith other therapeutic services.

For example, an investigatormay wish to develop a four

session, highly focused, jobseeking skills module that can

be easily implemented by awide range of practitioners toeffectively increase appropriate

job seeking behavior. Otherexamples include, but are not

limited to, modules to engageambivalent drug dependent

individuals in treatment,modules to increaseassertiveness in female drug

addicts who feel pressured byothers to use drugs, or to

incorporate effective HIV riskreduction techniques.

c. Therapies designed specifically

to engage and retainindividuals in treatment,especially those at high risk for

HIV. An example could be atherapy that is: (1) sensitive tothe motivational level of the

client; (2) is specificallydesigned to respond to the

needs of the individual,whatever his or her

motivational level might be;and (3) actively works toincrease an individual's desire

to remain in treatment.

d. Therapies designed tointervene with understudiedpopulations including users of

drugs such as MDMA andother club drugs, marijuana,

and inhalants, as well aspersonality disordered drug

abusers.

e. Therapies for drug abusers

who are not yet dependent ondrugs to reduce risk of

escalation to dependence andtherapies for drug abusers whohave not considered or claim

little interest in seeking

treatment for their drugproblems. For thesepopulations treatments are

needed which interest andengage the potential client andintervene with them.

Treatments which participantsin their natural environment,

such as treatments deliveredover the Internet or in

neighborhood settings such aschurches and recreationcenters are desired.

Lisa Simon Onken, Ph.D.(301) 443-0107

Email: [email protected]. Development of HIV Risk

Reduction Interventions. Researchto develop and evaluate behavioralstrategies to reduce HIV riskbehaviors in HIV-positive and HIV-

negative substance abusingtreatment populations. Risk

reduction interventions should bespecially adapted to patients age,

gender, cultural background andpotential cognitive impairments andshould address compliance with

medical regimens. The product ofsuch research might be

educational materials, such asmanuals or videotapes that

describe the intervention and itsimplementation by treatment staff.


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10. Complementary and AlternativeTherapies (CAT) for Drug AbuseTreatment. Research isencouraged on complementary andalternative interventions for drug

abuse treatment. CAT interventionscould be the sole treatment or

could be adjunctive strategies to

enhance the therapeutic potency ofexisting drug abuse treatments. Anexample of an adjunctive CATintervention might be where the

intervention reduces withdrawalsymptoms thus enhancing

retention in treatment. Includedwould be interventions that are

commonly used in real worldtreatment settings, but whosetherapeutic efficacy has not been

scientifically demonstrated. Such

interventions include acupuncture,bioelectrical stimulation, exercise,biofeedback, meditation, among

others. The product of thisresearch might be a manual orvideo, which illustrates the

intervention and how it isimplemented by treatment staff.

11. Translation of Cognitive andAffective Neuroscience FindingsTowards Development ofBehavioral Treatments. Recentstudies using neuroimaging and

neuropsychological evaluationsprovide ample evidence thatchronic drug use is associated withneuroanatomical changes that alter

cognitive function and the ability toregulate affective states. Further,

these changes vary over time andmay depend on the current state of

the individual (e.g., acuteadministration of one or moredrugs; during initial vs protracted

abstinence). Such comorbid

conditions make it difficult for manychronic drug users to engage inand participate meaningfully in

efficacious behavioral drugtreatments. However, knowledgefrom neuroimaging and

neuropsychological studies has notyet been utilized to benefit the

patient. In addition, knowledgeabout fundamental cognitive and

affective functioning even in theintact brain, typically has not led to

tools that can be used for treatingsubstance abuse. Thus, researchthat integrates basic research

findings on cognition (e.g.,decision-making, problem-solving,

learning, memory, attention,

motivation) and affect (e.g.,anxiety, anger, depression) in thefollowing areas are encouraged:Development of interventions to (a)

reduce the negative impact ofcognitive dysfunction and affective

dysregulation on drug useoutcome; (b) prevent relapse; (c)

reduce the severity and course ofthe dysfunctions; (d) improvespecific areas of cognitive and

affective functioning; and (e)

improve daily functioning inaddition to reducing clinicalsymptoms. Other goals of this

initiative are to: Develop reliableand valid methods for assessingbasic cognitive and affective

processes as part of clinicaldiagnosis; evaluate cognitive and

affective functioning as indicatorsof risk for exacerbated drug use

during treatment or for developingother disorders; determine if andhow current efficacious treatments

rehabilitate altered cognitive andaffective functioning; modify and

test current efficacious treatmentstailored to the needs of cognitively

impaired individuals.

Mary Ann Stephens, Ph.D.

(301) 443-0107

Email: [email protected]. Incorporating Smoking Cessation

in Drug Abuse Treatment.Research is encouraged to developand test behavioral treatments for

nicotine-addicted individuals whoalso are addicted to othersubstances, such as heroin,

cocaine, methamphetamines andalcohol. Prevalence of cigarette

smoking is extremely high amongdrug dependent individuals

attending drug treatment. Manytreatment providers are reluctant to


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address smoking cessation withclients either because they believe

that substance abusers are notinterested in quitting or becausethey fear smoking treatment will

have a negative impact on drugabuse treatment outcome.

However, studies have shown that

many drug abuse clients areinterested in quitting smoking andthat the concurrent treatment oftobacco dependence and other

drug dependencies does notthreaten abstinence and might

even assist in maintaining it.Research is needed to develop and

test smoking cessation treatmentsthat can be incorporated intotreatments for illicit drugs of abuse.

13. Developing Treatments for

Smokers with Comorbid Disorders.Research is encouraged thatfocuses on the development,

refinement, and testing ofbehavioral treatments for smokers

with psychiatric comorbidity, suchas depression, schizophrenia, or

anxiety disorders. Smokingprevalence is very high inindividuals with psychiatric

disorders. These populationsgenerally respond poorly to

traditional smoking cessation

treatments. Research is needed todevelop and test innovativebehavioral and combinedbehavioral and pharmacological

treatments that address the uniqueneeds of these individuals.

Ms. Debra Grossman(301) 443-0107

Email: [email protected]. Development of New or Improved

Addiction Assessment Measuresand Procedures. Research directed

at the improvement of a currentlyavailable measure or the design of

a new psychosocial, social orenvironmental measureappropriate for use in the clinical

assessment of substance abusingpopulations. Special consideration

should be given to a specificscreening or diagnostic tool, or to a

specific measure of treatmentreadiness, treatment compliance,

service utilization, therapeuticprocess or drug treatmentoutcome. The NIDA DTR&D

supports research aimed at thedevelopment and testing of

pharmacological and behavioral

treatments for drug abuse andaddiction. This includes theidentification, evaluation,development, approvability, and

efficacy testing of new andimproved pharmacotherapeutic

agents, as well as the testing ofmarketed medications, and of

behavioral treatments used aloneor integrated with medications. TheDTR&D also advances a human

neuroscience research and training

program focused on understandingthe neurobiological substrates ofdrug abuse and addiction

processes.

15. Behavioral Therapies for Pre-Adolescents and Adolescents.Behavioral therapies for pre-

adolescents and adolescents thatincorporate HIV risk reductioncounseling as an integral

component of the treatment. Thisincludes the development of new,

or refinement of existing

psychotherapies, behavioraltherapies, and counseling (groupand/or individual). This alsoincludes the development and

testing of manuals as well as othercreative, interactive approaches for

therapy delivery that may considerdifferent settings for delivery, such

as primary care, school-basedhealth programs, juvenile justicesettings, etc. Also the behavioral

treatments should be culturally and

gender sensitive.16. Behavioral Therapies for Couples

and Families. This includes thedevelopment of new psychotherapyapproaches, the modification or

testing of existing behavioraltreatments, and the design and/or

testing of innovative clinical trainingand supervision methods for


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dissemination of efficacioustreatments to community settings.

Treatments that target domesticviolence or other forms ofinterpersonal abuse along with

substance abuse are encouraged.

17. Behavioral Therapies for Groups.

This includes the development ofnew psychotherapy approaches,

the modification or testing ofexisting behavioral treatments, and

the design and/or testing ofinnovative clinical training andsupervision methods for

dissemination of efficacioustreatments to community settings.

Examples of relevant projects are:traditional group therapies, such as

12-step and therapeutic communityapproaches, and newer group

therapies such as cognitive-behavioral and acceptance-oriented approaches; groups for

various populations, such asadolescents, adults, couple and

family groups, gender-specificgroups, and groups tailored for

racial or ethnic minoritypopulations. Of particular interestare projects that address the recent

findings suggesting possiblecontraindications of group

treatments for some populations

(e.g., delinquent adolescents), or insome formats (e.g., less-structured,emotion-focused grouptreatments).

18. Behavioral Therapies Drawing fromStress Research or Stress-Management Interventions.Projects are encouraged that apply

concepts from stress research(such as appraisal, coping, and

social support) to drug abuse ininnovative ways, or that test the

extent to which stress-management interventions can beapplied to the treatment of drug

abuse and interventions to reducerisk of HIV and other infectious

diseases. Examples of stress-management techniques that may

have novel application to drugabuse and HIV risk include

techniques that teach problem-solving and affect-management,

restore ones sense of purpose andmeaning, prevent burnout in theface of chronic stressors, increase

self-efficacy for managing stress,inoculate against stressors, train

relaxation and meditation,

intervene during crises, enlistsocial support and system support,and others.

Melissa W. Racioppo, Ph.D.(301) 443-0107, Fax: (301) 443-6814

Email: [email protected]. Modifying Efficacious Behavioral

Treatments to be CommunityFriendly. Several behavioralinterventions have been found to

be efficacious for the treatment ofdrug addiction. However, there are

barriers to implementation ofbehavioral therapies in community-

based settings. Communitysettings that treat drug addictedindividuals are reluctant or

unwilling to adopt theseinterventions for a variety of

reasons. Reasons thatscientifically-based behavioral

treatments are not accepted bycommunity providers could include

the excessive cost ofimplementation, the length of timefor administration of treatment,

inadequate training available fortherapists and counselors,

treatments not shown to begeneralizable for different patient

populations or for polydrug abusingpopulations, etc. Research aimedat modifying efficacious behavioral

treatments to make them moreacceptable to community settings

is needed. Settings might include,drug abuse treatment facilities,

primary care, managed care, andthe criminal justice system.Examples of possible studies are

those that are designed to reducethe cost of implementation of

treatments, reduce the time ofadministration of treatments, aid in

training of therapists, counselors


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and nurses, adapt individualtherapies for group situations, etc.

20. Innovative Technologies for DrugAbuse Treatment, HIV RiskReduction, and Training Clinicians.Relevant research would bedirected at the development and

evaluation of innovativetechnologies to treat substance

abuse, enhance adherence tomedications, and/or reduce risk for

HIV infection or transmission.Approaches should be capable ofbeing readily incorporated at

reasonable cost into varioustreatment settings. Areas of

interest include Internet-basedtreatment or training programs,

CD-ROM technology, audiodelivery devices, photo therapeutic

instruments, and hand-heldcomputers. Also of interest arecreative approaches for

disseminating science-basedbehavioral treatments and for

training therapists to usescientifically based treatments for

drug abuse and addiction. Suchapproaches might include Internet-based education, interactive

computer programs, telemedicine,etc. Finally, approaches which

apply therapies with evidence of

efficacy through new media suchas web-based platforms, overemail, or through chat rooms andbullet boards are also desirable.

21. Virtual Reality Applications for DrugAbuse Treatment ProviderTraining. Recently virtual realitysimulations have been used to train

medical personnel in demandingmedical procedures such as

microsurgery techniques. Virtualtraining allows trainees to gain

familiarity with both theenvironment in which services aredelivered as well as the

intervention techniques without thedanger of mistakes impacting live

patients. Virtual reality interfacescan assess skill acquisition and

provide detailed feedback duringprocedures to help trainees correct

mistakes or avoid making themaltogether. In the drug abuse field,

training and dissemination effortshave been hampered by a dearthof knowledge about ways to

conduct dissemination. Althoughtrainees often practice on actual

clients, this approach has

drawbacks including its reliance onthe client or participants scheduleand willingness to participate intraining sessions and potential

danger to the client or if theintervention is delivered incorrectly.

Libraries of virtual realitysimulations of drug users in

treatment or virtual patients areneeded to provide experientialtraining for treatment providers

without relying on existing patients.

This will help facilitate the rapidand effective dissemination ofproven treatment strategies.

Cecelia McNamara, Ph.D.(301) 443-0107, Fax: (301) 443-6814

Email: [email protected]. Clinical Neurobiology Branch (CNB).

The CNB supports research on thebiological etiology (determining the

biological basis for vulnerability to drugabuse and progression to addiction,

including studies on individualdifferences and genetics) and clinicalneurobiology of addiction (exploring

alterations of the structure and/orfunction of the human central nervous

system following acute or chronicexposure of drugs of abuse), and the

neurobiology of development(neurobiological effects of drugs ofabuse and addiction during various

stages of development and maturation,effects of drug exposure on

neurobiological processes,development of methodologies and

refinement of techniques used inpediatric neuroimaging). The Branchalso supports investigations on the

cognitive neuroscience of drug abuseand addiction, the neurobiology of

treatment, neuroAIDS, and human painand analgesia. Areas that may be of

interest to small businesses include,but are not limited to:


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1. Development of Novel Approachesin Human Neuroscience.Development of innovative,noninvasive research methods ornovel approaches are needed to

identify various neurobiologicalmarkers of brain alterations in

humans induced by acute or

chronic exposure drugs of abuse.This may include the identificationof neurobiological (includinggenetic) markers that might be

associated with risk for, orresilience to drug abuse and

addiction. Of particular interest arenoninvasive methods (e.g., brain

imaging) that could be used todetermine the effects of drugabuse/ addiction treatments on

neurobiological systems in an

attempt to understand theneurobiological processesunderlying therapeutic efficacy.

In recent years, there has been anincrease in studies employing

functional magnetic resonanceimaging (fMRI) to understand brain

processes and functional neuronalsystems. In particular, theseneuroimaging techniques are being

used to probe how drugs of abusealter brain functioning.

Consequently, there is a need for

the development of stimulusgeneration hardware to be usedwithin an fMRI magnet that candisplay stimuli important in drug

studies. As the studies of brainfunction become more

sophisticated, task-relatedassessments of brain activation are

increasingly important. Shieldedgoggles or other types of stimulus-generating hardware and software

are necessary for presentation, for

example, of neurocognitive tasks,drug-related images for theinduction of craving, or other

virtual reality types of dynamicstimuli important in studies of drugabuse and addiction. Responses to

this type of stimulation then couldbe correlated with brain measures

using neuroimaging techniques.These types of studies will provide

new insights into drug-brain-behavior interactions.

Development of the human centralnervous system and how drugs of

abuse perturb this process is ofgreat interest. Little is currentlyknown about the effects of

exposure to drugs of abuse, eitherprenatally or during childhood or

adolescence, on the developmentof the human nervous system.

Further, the application of newlyemerging technologies (such asneuroimaging) to these populations

presents unique challenges due tothe fact that the central nervous

system, and its capabilities, arechanging rapidly. The development

of novel techniques, or therefinement of existing methods, to

provide direct noninvasivemeasures of brain structure and/orfunction that are adapted

specifically for use in pediatric andadolescent populations is strongly

encouraged. Also, neurocognitiveand other neurobehavioral tasks foruse in these populations, especially

where they can be designed toprobe underlying neurobiological

processes, need to be developed.

Joseph Frascella, Ph.D.

(301) 443-4877Email:[email protected] Stanford, Ph.D.(301) 443-4877

Email: [email protected]. Virtual Reality for the

Neurobiological Study of Drug-Brain-Behavior Interactions andDrug Abuse Treatment. VirtualReality (VR) is an emergingtechnology useful in a variety of

research-related, therapeutic andinstructional settings. By immersing

a persons senses in a syntheticworld or Virtual Environment (VE)

that characterizes VR, a highlyflexible and programmable set ofstimuli can be used to enhance the

standard approaches used inassessment of neurobiological and

neurobehavioral processes.


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Collection of real-time data andbulk data recording can provide a

correlation of a stimulus referencesignal with simultaneouslycollected fMRI scanner and

physiological data over time. Unlikemost computer access systems

that accept only one or two modes

of precise and/or discrete input at atime, VR systems have thepotential to monitor movement oraction from any, or many,

neurobiological functions at once.In addition, the multimodal

feedback inherent in VR provides away to vary nonvisual stimulus

components (e.g., resistance,temperature, pitch) in a way that isimpossible to achieve via standard

computer systems. Finally, VR

systems provide a bypass forkeyboard entry or directmanipulation environments (e.g.,

pointing instruments like themouse), by allowing themanipulation of multi-sensory

representations of entireenvironments by natural actions

and gestures.

VE can provide a completely

controlled, noninvasive, safe andalternative methodology for a

variety of important studies of drug

abuse and addiction. For example,VR allows for the presentation of avariety of complex, multi-sensorystimuli for neurocognitive tasks or,

alternatively, the dynamic stimuliimportant for producing drug-

related images for the induction ofcraving. VR can also be tested as

an alternative to traditionalbehavioral therapies in thetreatment of drug abuse.

Responses obtained as a result of

the above can then be correlatedwith brain measures using state-of-the-art neuroimaging techniques.

We, therefore, invite studiesemploying VR, especially to probebrain processes in drug

abuse/addiction combined withneuroimaging methods or to be

developed or applied as a potentialtreatment for substance abuse.

Ro Nemeth-Coslett, Ph.D.(301) 402-1746

Email: [email protected]. Development of Interactive

Computer Applications forNeuropsychological/Neurocognitive Assessment toDetermine Functional Brain Deficitsin Acute and Chronic DrugAbusers. In addition, aneurobehavioral test battery to

assess otherneurobehavioral/neurocognitive

deficits resulting from drugabuse/addiction is encouraged. Ofparticular interest is the

development of such assessmentsfor use in children and adolescents

exposed to drugs of abuse to betterdefine and understand the effects

of early exposure on brain functionand development (fordevelopmental issues, contact

Larry Stanford, Ph.D.).

Steven Grant, Ph.D.

(301) 443-4877

Email: [email protected] Stanford, Ph.D.(301) 443-4877

Email: [email protected]. Development of Ligands for Brain

Imaging. Development of novelradioligands for PET and SPECT

imaging in human brain formolecular targets (e.g., receptors,intracellular messengers, disease-

related proteins) is of broad interestto the neuroscience and drug

abuse research community. Theprimary application of these

radiotracers will be in basicneuroimaging research. Ultimately,these radiotracers may also be

used as potential biological

markers and surrogate endpointsfor translational and clinicalresearch, drug discovery and

development, and clinical trials.The scope of the projects mayencompass pilot or clinical

feasibility evaluation in pre-clinicalstudies, model development, or

clinical studies. Alternatively, the


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focus may be on research anddevelopment of new technologies

for radiotracer development.

Steven Grant, Ph.D.

(301) 443-4877

Email: [email protected]. Novel Approaches in the Clinical

Neurobiology of Drug Addiction.Given the array of interdisciplinarysolutions across the NIH for avariety of existing conditions, NIDA

has a strong interest in novelapproaches, devices and

strategies, which have not, untilnow, focused on the drug abuse

arena. We, therefore, inviteproposals to determine which, ifany, pre-existing assessments,

research tools and/or interventionstrategies can be effectively

applied to issues specificallyrelated to neurobiology of human

drug abuse and the addictionprocess (e.g., neurobiologicmechanisms underlying drug

abuse or addiction,neurobiologic/genetic determinants

of risk/protective factors, theprevention of initiation, the onset of

dependence, the longevity ofmaintenance, the termination ofuse and the mitigation of residual

neurobiologic sequelae). As anexample, under a separate

announcement (see above), NIDAhas solicited and continues to

solicit proposals using virtual realityto increase our understanding of

the neurobiology of addiction, (e.g.,drug cues, craving), comorbidity(e.g., post-traumatic stress

disorders) and pain (e.g.,distraction). Additional novel

approaches, devices and strategiesare now being sought to further our

understanding of the cognitiveneuroscience of drug abuse andaddiction, neuroplasticity and

repair, the neurobiology oftreatment (including training tools,

assessment and neurolobiologiccorrelates of treatment outcome),

neuroAIDS, and humanpain/analgesia. Techniques such

as hyperbaric oxygenation, used toincrease oxygen in blood in

experimental and treatmentprotocols, may improve drug-induced cognitive deficits.

Transcranial magnetic stimulation,utilized to modulate cortical

excitability, deep brain stimulation

to improve refractory comorbidconditions, and biofeedback controlof cortical function are otherexamples of untested possibilities

in the study of addiction. We arecasting a wide, interdisciplinary net

to encourage cutting-edge, state-of-the-art proposals. As with all

NIDA-funded research, theconceptual framework, design,methods, and analyses must be

adequately developed, well-

integrated, and appropriate to theaims of the project. The applicantmust acknowledge potential

problem areas and consideralternative approaches. Whereasthe proposal must employ novel

concepts, approaches or methodsthat are not mainstream to drug

abuse, the inclusion of establishedanalytic tools to determine the

efficacy of the approach isrequired. The aims must be originaland innovative and the proposal

should challenge existingparadigms or develop new

methodologies or technologies. Inaddition, the investigator must be

appropriately trained and wellsuited to carry out this work andthe work proposed must be

appropriate to the experience levelof the principal investigator and

team of other researchers (if any).

Ro Nemeth-Coslett, Ph.D.

(301) 402-1746

Email: [email protected]. Medications Research GrantsBranch (MRGB). The MRGB supports

investigations of the use of therapeuticagents (including vaccines and

monoclonal antibodies) for thetreatment of substance related

disorders, with the aim of assisting inreducing drug use, becoming drug free,


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prolonging abstinence, decreasingassociated psychosocial, medical or

legal problems, or surviving drugoverdose. In general, therapeuticagents are expected to be investigated

using a platform of appropriatepsychosocial interventions. The

program funds extramural grants in the

following areas:

Clinical trials to test the safety, find

the optimal dose, and/or obtainpreliminary efficacy data for newagents or new indications of

marketed medications. This phaseincludes interaction studies to test

the safety of the agent when used incombination with drugs of abuse.

Clinical trials to assess the efficacy

of new agents or marketed

medications for the treatment ofsubstance related disorders. Ingeneral, these types of trials use arandomized double blind placebocontrolled design.

Clinical studies of the efficacy of

medications for the treatment of thecomorbidity of substance related

disorders (e.g., alcohol and cocainedependence) or the comorbidity of

these disorders with other medicalor psychiatric conditions.

Clinical evaluation of the efficacy of

medications for the treatment ofsubstance related disorders in

specific groups of the population.For example, adolescents, the

elderly, women of childbearing age,pregnant and/or postpartum women,

as well as racial and ethnicminorities.

Evaluation of biological and/or

psychosocial factors that may affect

the outcome of thepharmacotherapy of substancerelated disorders.

Specific areas that may be of interest to

small businesses include, but are notlimited to:

1. Pharmacogenetics and SubstanceUse Disorders. The emergence of

new genetic techniques may allowthe use of genetic information to

improve the safety and efficacy oftreatments. The field ofpharmacogenetics focuses on the

genetic determinants of responseto medications and other in

humans and animals. The goal is

to discover novel single nucleotidepolymorphisms (SNPs) and testtheir relevance to the underlyinggenetic differences that determine

the safety and efficacy ofmedications for the treatment of

SUD. It includes the study of genesencoding drug metabolizing

enzymes, transporters, receptorsand other drug targets, polygenicdeterminants of drug disposition

and effects in humans, the role of

genes in the clinical response toand medical safety of medications,and application of genetic

information to disease preventionand to optimize treatments inhumans. It also includes novel

methods for phenotyping thediagnosis, safety and treatment

outcome of SUD. Ultimately, it isexpected that pharmacogenetics

research will help clinicians toindividualize the treatment of theirpatients based on their genetic

information. Research is needed tostudy the genetic factors that may

be associated with drug abusetreatment safety and outcome.

2. Medications Development for theTreatment of Drug Abuse inAdolescents. Drug abuse amongadolescents is a significant and

growing public health concern. It isknown that the pharmacokineticsand pharmacodynamics of some

medications are different in

adolescents. Therefore,adolescents may presentoverdoses, underdoses or lack of

efficacy, or different safety profileswhen administered medications atthe doses studied only in adults.

Unfortunately, little is known aboutthe safety and efficacy of

medications for the treatment ofdrug abusing adolescents because


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most of the drug abuse medicationresearch has focused on adults.

Research is needed to testmedications for the treatment ofnicotine and drug abuse in

adolescents.

3. Medications for the Treatment of

Pregnant and Post-Partum DrugAbusing Women and TheirChildren. Little is known about thesafety and efficacy of medications

for the treatment of substanceabusing pregnant women and theirchildren. There is a need for safe

and effective medications for thetreatment of nicotine and drug

abuse among pregnant and post-partum women and the effect of the

medications on their children.Research is also needed to study

the effects on the newborn of themedications taken by the motherand medications for treatment of

children born to substance abusingmothers who may present drug

withdrawal and other symptoms.

4. Medications for the Treatment ofComorbid Medical or MentalDisorders and Drug Abuse.Comorbid medical and psychiatricconditions are frequently foundamong substance abusing patients.

Co-occurring mental disorders,such as depression, post-traumatic

stress disorder, and anxietydisorder, and medical conditions

such as hepatitis C, AIDS relateddisorders, and pain, are commonamong substance abusing patients.

Unfortunately, there are presentlyno commonly prescribed safe and

effective medications for thetreatment of substance abusing

patients with other comorbidmedical and psychiatric conditions.

Research is needed to study thesafety and therapeutic profiles ofmedications for treatment of

substance abuse in patients withother comorbidities. There is also a

need to study the effects ofmedications for the treatment of

substance use disorders in patientstaking medications for other

comorbid conditions and thenecessary dose adjustments.

5. Development of Software and/orOther Tools for Data Collection andStatistical Analysis of Clinical TrialsTesting the Safety and Efficacy ofTherapeutic Agents for the

Treatment of Substance RelatedDisorders. Current data collectiontechniques often have questionablevalidity and reliability and statistical

data analysis pose particularchallenges. These problemsinclude lack of well defined

outcome measures or having alarge amount of missing data,

which may be due to intermittentmissing data points or early subject

drop out (attrition). To solve thosechallenges, investigators have

developed pragmatic methods toanalyze their data. For example,carry forward data from the last

timepoint, data replacement byregression, end point analysis by

regression, or worst case scenario,they all have important statistical

limitations. The purpose of thisinitiative is to stimulate research oninnovative data management tools

to improve data collection andanalysis of data from nicotine and

drug abuse clinical trials.

Ivan D. Montoya, M.D.

(301) 443-8639

Email: [email protected]. Immunotherapy for Addiction

Treatment. The MRGB supportsresearch on the advanced stagedevelopment of monoclonal

antibodies and vaccines for thetreatment of drug and nicotineaddiction and/or overdose.

Monoclonal antibodies have beenreported as possible treatment

agents through passiveimmunization for PCP,

methamphetamine, MDMA, andcocaine overdose and may alsoserve to minimize abuse and

prevent relapse. New vaccines arebeing developed as therapies for

drug or nicotine cessation andrelapse prevention. New


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technologies, such as theproduction of antibodies in plants,

are emerging as cost-effective andefficient ways for the large scalemanufacture of immunotherapy

agents, represent another facet ofthis area for development.

Jamie Biswas, Ph.D.(301) 443-8096

Email:[email protected]. Development of GHB Detection

Kits and Antidotes to Treat GHBPoisoning. A DAWN report statesthat there were over 3000emergency room visits connected

to GHB poisoning in the UnitedStates in 2001. GHB poisoningresults in respiratory depression

and coma, and can be fatal.Clinical interventions are needed to

facilitate recovery from intoxicationand/or poisoning from gamma-

hydroxy butyric acid (GHB). Thereis also a need for the developmentof diagnostic kits for the rapid

detection of GHB, gamma-butyrolactone (GBL), and 1,4-

butane-diol (BD) in body fluids(plasma, saliva, urine). The method

of detection should be fairly rapidand specific, and could be eitherqualitative or quantitative.

Detection kits are needed to assistemergency room doctors in the

rapid diagnosis of GHB poisoning,which is very difficult and critical for

the selection of a proper treatmentstrategy. The availability of such

kits would aid in the reduction ofmortality and treatment costs.8.Development of Neurotechnologyfor the Treatment of DrugDependence. MRGB is interestedin clinical research evaluating theefficacy of emerging

neurotechnological diagnostic andtherapeutic modalities for treatingdrug dependence and addiction,

with particular emphasis onpsychostimulants, opiates, nicotine

and cannabinoids. An example ofsuch a therapy would be

Transcranial Magnetic Stimulation(TMS) of the brain. TMS is a

noninvasive technique currentlyused as a diagnostic and

therapeutic tool in neurology andpsychiatry. It has been reported toreduce symptoms of depression,

PTSD, OCD, epilepsy, migraine,Tourettes syndrome, Parkinsons

disease, and hallucinations in

schizophrenic patients. Thetherapeutic uniqueness of thistechnique lies in the relativeneuroanatomical specificity of its

effects, in contrast to generalizedeffects of pharmacotherapies. TMS

may be used to rapidly, eitherlaterally or focally, alter cortical

brain activity, which might behelpful in the treatment of drugdependence. Repetitive TMS may

alleviate drug craving by the brief

deactivation of certain brainregions. It may also improve moodand enhance cognition, thus

facilitating abstinence from drugs ofabuse and increasing effectivenessof cognitive therapies.

9. Research and Development ofPsychobiological Markers ofResilience or Refractoriness ofDrug Dependence as a Tool forOptimization of Treatment.Difficulties in finding rapid and

effective therapies for drug

dependence, especiallydependence on psychostimulants,appear to result, in part, from theheterogeneity of drug addicts

entering treatment programs ortrials. This heterogeneity may

ensue from differentpsychobiological and genetic

determinants, including psychiatriccomorbidities, which contribute tothe development and persistence

of drug dependence. Studies and

clinical observations show thatsome addicts recover relativelyeasily after standard treatments for

stimulant dependence, while othersrelapse early or drop out of thetreatment. Identifying

psychobiological markersdistinguishing different groups of

addicts may permit selection ofoptimal treatment strategies for


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these groups, which may or maynot include selective

pharmacotherapy in addition tostandard psychotherapeuticmodalities. Research is needed to

identify potential biological andpsychological markers, which

correlate with resiliency or

refractoriness of drug/stimulantaddicts. Identification of suchmarkers may guide development ofnovel treatments for drug

dependence. There is a need foranalytic kits for simultaneous

detection of several hormonessuch as PS, DHEAS, THP,

THDOC, cortisol and testosteronein body fluids, optimally in saliva.Detection kits for steroid hormones

may also have broader utility as

aids for diagnosis of otherpsychiatric disorders, such asdepression and PTSD.

Maria D. Majewska, Ph.D.(301) 443-9807


Division of Neuroscience and BehavioralResearch (DNBR)

DNBRs basic neuroscience and

behavioral research focuses on

understanding the mechanisms,characteristics, and processes of drug

abuse. Basic behavioral, cognitive,neurobiological, cellular, molecular,

chemical, and genetics research aims at

characterizing and understanding drugseeking, compulsive behavior, and

addictive processes. These research

areas necessarily include studies of

normal processes.Using both animal and human studies,

basic behavioral research focuses onbehavioral and cognitive processes thatmay or do lead to drug initiation, and the

behavioral and cognitive consequences

of drug abuse. Neurobiology researchfocuses on the neural mechanisms and

substrates underlying behavioral and

cognitive processes and vulnerability

factors associated with drug abuse,

addiction, sensitization, tolerance, andrelapse.

DNBR supports basic chemistry and

pharmacological studies focusing onstructure/activity relationships,

definition, and characterization of

systems involved in drug actions,

chemical synthesis of new ligands,pharmacokinetics, analytical methods,

understanding basic mechanisms of drug

action and drug testing.Computational and theoretical modeling

of biological systems and behavioral

processes, biomedical computing and/orinformation science and technology

development is supported by DNBR.A. Research Related to the Design of New

Therapeutic Approaches.Development of new therapeutic

approaches based on the application ofnanoscale particle formulations for

drugs that are either poorly water-soluble or otherwise unstable under

physiological conditions, anddevelopment of methods for usingnanoscale formulations for targeting

specific brain sites or to control drugdelivery over extended periods of time.

Thomas G. Aigner, Ph.D.

(301) 443-6975Email: [email protected]. Virtual Reality for Treatment of Pain.

Recent findings (Hoffman et al., 2000,Pain, 85, 305-309) have suggested that

Virtual Reality (VR) exposure canreduce reported pain during wound

care. Grant proposals are sought toexamine the utility of VR technologiesin the treatment of various types of

pain. Development of treatments forboth acute and chronic pain are sought.

These treatments can be based in

clinical settings or the patients homes.Phase I testing should establish thefeasibility of the use of this technologyin the particular population to be tested.

Phase I should also produce data thatdemonstrates that this methodology is

effective for the particular type of painbeing treated. Phase II should involve

larger-scale testing (e.g., more subjects


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and treatment trials) examining varioustreatment parameters (e.g., timing of

treatment, types of VR environments).The focus of Phase II testing should bethe refinement of this treatment for use

in pain patients.

C. Virtual Reality for the Treatment of

Drug Abuse. Recent findings (Hoffmanet al., 2000, Pain, 85, 305-309) have

suggested that Virtual Reality (VR) canbe a useful clinical tool. In this

particular study, VR exposure wasused to allow patients to selectively notattend to an otherwise painful

procedure. Drug abuse, like pain, is aproblem that is strongly impacted by

stimuli in the abusers environment andpsychological factors. Thus, it is

reasonable to assume that VR may beuseful in allowing individuals to ignore

drugs cravings, withdrawal symptomsor environmental cues that promotedrug abuse. Grant proposals are

sought to examine the utility of VRtechnologies in the treatment of various

types of drug abuse. These treatmentscan be based in clinical settings or the

patients homes. These treatments canbe developed to address drugwithdrawal, drug craving or on-going

drug related behaviors. Thedevelopment of VR technologies to

address abuse of all types of drugs

(e.g., cocaine, marijuana, nicotine,alcohol, inhalants) are sought. Phase Itesting should establish the feasibility ofthe use of this technology for the

particular drug problem addressed(e.g., cocaine craving, opioid

withdrawal) and should also producedata that demonstrates that this

methodology is effective for theparticular drug problem. Phase IIshould involve larger-scale testing

(e.g., more subjects and treatment

trials) examining various treatmentparameters (e.g., timing of treatment,types of VR environments). The focus

of Phase II testing should be therefinement of this treatment for use inthe treatment of drug abusers.

David Thomas, Ph.D.

301-443-6975


D. Chemical Libraries for DrugDevelopment. The development andbiological screening of lead compoundsand their combinatorial libraries for usein the area of drug abuse treatment

research are encouraged, such asgeneration of new ligands having

opiate receptor selectivity, or ligands

with NMDA or serotonergicagonist/antagonist activity and/orrelated. These are designed as leadcompounds either for drug design or as

tools to elucidate mechanisms of actionof drug abuse.

Hari H. Singh, Ph.D.(301) 443-6300

Email: [email protected]. Genetic Studies. The National Institute

on Drug Abuse is interested in SBIRproposals that would greatly facilitate

the identification of genetic loci thatconfer vulnerability to substance abuse

and addiction. Areas of interest includebut are not limited to:

1. Collection and genotyping ofhuman pedigrees and sib-pairs for

vulnerability or resistance to drugabuse.

2. Isolation and identification ofmutant strains in genetic model

systems such as Zebrafish,Drosophila, C. elegans, mice, andrats that are more vulnerable or

resistant to drugs of abuse.

3. Design, development, and

marketing of behavioralapparatuses to conduct rapid

behavioral throughput screens foridentifying genetic vulnerability to

addiction in genetic modelsystems.

4. Development of transgenic modelsfor drug abuse using bacterial

artificial or yeast artificialchromosomes.

5. Development of software anddatabases for candidate genes fordrug abuse.

6. Identification and mapping of

functional polymorphisms ofcandidate genes for drug abuse.


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7. Placement of candidate genes fordrug abuse on biochips.

8. Marker-assisted breeding ofcongenic mouse and rat strains for

mapping quantitative trait lociassociated with addiction and drugabuse.

9. Vectors for gene transfer intoneurons.

Jonathan Pollock, Ph.D.

(301) 443-6300

Email:[email protected]. Drug Testing Development.

Development of new, more refined or

more practical drug testingmethodologies. Studies may focus, butare not limited to the following topics:

drug testing methods; drug extractionprocedures; methods to control for

possible environmental contaminationfactors; and reference materials.

Methodologies with special applicationto the workplace, the emergency room,the transportation environment, or other

specific settings are welcome.Methodologies with an emphasis upon

circumstances for testing such as post-accident testing or readiness for work

testing are also encouraged.

Beth Babecki, M.A.

(301) 443-1887

Email: [email protected]. Effects of Drugs at the Cellular Level.

Development of new imaging

techniques, reagents and relatedhardware and software for dynamic

investigations of the effects of drugs ofabuse on cellular activities andcommunications. For example, these

techniques might include, but are notlimited to, development and utilization

of reagents for magnetic resonancemicroscopy and other MRI methods;

development of methodologiesapplying functional MRI to drug abusestudies; the use of dyes, intrinsic

signals, and other optical indicators forstudying signal transduction

mechanisms, the regulatory control ofprotein entities (such as

phosphorylation), and neuronalexcitatory and inhibitory pathways.

Areas of interest may include, but arenot limited to:

1. Studies using molecular biologicaltechniques to scale-up protein

production for investigations aimedat enhancing understanding of thestructure, function and regulation of

molecular entities involved in thecellular mechanisms through which

abused drugs act.

2. Validated in vitro test systems can

reduce the use of animals inscreening new compounds that

may be of potential benefit intreating drug abuse. Test systems

are needed to evaluate activity atreceptors or other sites of action,explore mechanism(s) of action,

and assess potential toxicity.

3. With the recent success inmolecular cloning of various drugabuse relevant receptors,

enzymes, and other proteins,researchers will elucidate the

molecular mechanism of action ofthese drugs. Studies to generate

strains of transgenic animalscarrying a gene of interest aresolicited. Of special interest are

knockout and tissue-specificknockout animals. These animals

can be used to identify gene

function, and to study thepharmacological, physiological,and behavioral role of a singlegene.

Jonathan Pollock, Ph.D.(301) 443-6300

Email:[email protected]. Toxicity Studies

1. Studies on abused drugs and their

metabolites to developmethodologies that may be

potentially useful in addressingmedical emergencies. Such studiesmight include investigations

involving development ofpharmacokinetic models,

methodologies, and data.

2. Concern remains about the

potential acute and chronicneurotoxicity of drugs of abuse.


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Information is needed about thepossible neurotoxicity of

pharmacotherapeutic agents withpotential for treating drug abuse.Improved methods are needed for

identifying, assessing, andquantifying the nature and extent of

neurotoxicity. Such studies might

include the development orapplication of quantitativechemical, physiological, orbehavioral measurements relating

to nervous system injury ormethods for quantitative analysis of

damage.

I. Predisposition to CardiovascularComplications Associated with AbusedSubstance(s). Development ofexperimental animal models to assessa genetic predisposition or increased

sensitivity to cardiac and vascularcomplications associated with druguse. Such studies might include, but

are not limited to, investigationsinvolved with biochemical, physiological

and pathological indices ofcardiovascular system function.

Pushpa V. Thadani, Ph.D.(301) 443-6300

Email: [email protected]. Opioid Peptides. Research and

development directed at the medicinal

chemistry and molecular pharmacologyof opioid peptides, especially inmethods development. Areas ofinterest include but are not limited to:

1. Development of innovative

methodologies for the synthesis ofopioid peptides to be madeavailable to researchers.

Syntheses proposed should belimited to single analogs.

2. Methods to identify new ligands foropioid receptors and the design of

new opioid peptide analogs withtherapeutic potential.

3. Development of analyticalmethodologies for the quantitation

of synthetic and endogenous opioidpeptides, peptide precursors, and

processing enzymes. Theinnovation may be limited to a part

of the method, such asdevelopment of a special detector

or a sample cell. Methods mightinclude antibody development anddevelopment of innovative

immunoassays.

K. Dopamine and Serotonin Receptor

Ligands. Both dopamine and serotoninreceptors exhibit multiple subtypes.

Applications are solicited usingchemical combinatorial library

techniques to develop ligands having ahigh degree of selectivity to thesereceptor subtypes, which can be useful

both as pharmacological tools and leadcompounds in medicinal chemistry/drug

development.

Rao Rapaka, Ph.D.

(301) 443-6300

Email: [email protected]. Systems Biology. The NationalInstitute on Drug Abuse is interested in

SBIR proposals that would facilitateglobal analysis of biological systems

relevant to drug abuse. Technologiesand resources developed should be

applicable and relevant to drug abuseresearch. Areas of interest include, butare not limited to:

1. Improved technology for analysis of

membrane proteomes for theidentification of targets andvalidation of leads.

2. Development of technology or newstrategies that will improve

dynamic range to allow theanalysis of a broader spectrum of

the proteome of neural cells.

3. Single cell analysis and the

development of model systems forproteomic analysis of neuronal

function and drug effects.

4. Development of real-time

proteomics technology for theanalysis of processes such as

cellular responses to drugexposure.

5. High throughput, high resolution3-dimensional in situ proteome

profiling such as optical projectiontomography, improved methods for


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high throughput sectioning ofneural tissue and the development

of tools for identifying and mappingprotein expression, localization andmovement relevant to addiction

and other medical consequencesof drug abuse.

6. High throughput, functional,molecular interaction screening

methods for proteins implicated indrug abuse.

7. Strategies to characterize post-translational modifications related

to addiction and drug effects.

8. Development of proteomic tools for

identifying biomarkers to tracktherapeutic efficacy, to monitor

effects of drug interactions, and toadvance biological understanding

of relationships between drug useand infectious disease, andtherapies for HIV, hepatitis C and

other diseases.

9. Development of computational

tools such as knowledge bases,information systems and

computational models for proteindata related to addiction and other

medical consequences ofsubstance abuse. Tools thatenable the integration of

proteomics, genomics,transcriptomics, metabolomics and

other data into applications leadingto systems understanding of drug

effects upon biological systems.

10. Technologies to identify

parameters of molecular, cellular,or physiological systems important

in addiction, and the properties ofthe system, such as redundancyand robustness.

11. New approaches for characterizing

cell phenotypes and mapping thosephenotypes.

Karen Skinner, Ph.D.(301) 443-6300

Email: [email protected] Colvis, Ph.D.(301) 443-6300

Email: [email protected]. Research Resources. The National

Institute on Drug Abuse is interested inSBIR proposals that would generate

the following resources for drug abuseresearch:

1. Resources for the application of

genetic engineering to dynamicallymonitor neuronal function.

2. C57BL6 Mouse embryonic stem

cells and spermatogonial stemcells.

3. Turnkey technology for proteomicssuch as the development of protein

and peptide chips to study drugeffects on neuronal mechanisms.

4. Antibodies, aptamers, ligands, etc.relevant to drug abuse research.

Jonathan Pollock, Ph.D.(301) 443-6300

Email:[email protected]. Development of Innovative Pulmonary

Nicotine Delivery Systems. NIDA isseeking SBIR grant applications for

development of devices that achievethe pulmonary delivery of nicotine inhuman subjects. A major effort in

smoking cessation centers on nicotinereplacement. Pulmonary delivery of

nicotine should permit more reliable

replication of the delivery that occursduring the inhalation of tobacco smoke.Thus, such devices would provevaluable as resources in support of

research studying the efficacy of rapidnicotine replacement, and as potential

future aids in smoking cessation. Thedevices should be small, portable, and

deliver a smoking-dose of nicotine ina reliable manner.

Allison Chausmer, Ph.D.(301) 402-5088

Email: [email protected]. Development of Innovative SyntheticProbes, Drug Dosage Forms, and/orDrug Metabolites For Drug AbuseResearch. Proposals are solicited forthe synthesis of new chemicalcompounds, drug metabolites,

peptidomimetics, and/or developmentof drug dosage forms for studying the


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mechanism of action of drugs of abuseand drug addiction.

Specifically proposals are encouragedin the following areas:

1. Synthesis of chemical probes, drugmetabolites, peptidomimetics,

and/or development of drug

dosage forms that are needed bydrug abuse research investigators,and they are not commerciallyavailable, and/or available with

great difficulty.

2. Alternate synthetic methods for

existing chemical probes thatimprove the yield and produce

these chemicals at lower costs ascompared to commercially

available substances.

3. Development of alternate drugdosage forms of existingdrugs/drug products for enhancing

their efficacy.

Hari H. Singh, Ph.D.

Phone: (301) 435-1310

Email: [email protected]. Development of Analytical Techniques.

The development of new analytical

methods for measuring drugs of abuseand their metabolites in biological

matrices, such as urine, blood, saliva,sweat, hair, breast milk, brain tissue,and meconium is encouraged. The new

methods should be efficient, sensitive,convenient, and cost effective.

Modifications and improvements inexisting analytical techniques are also

encouraged particularly thoseimproving sensitivity and selectivity.

Hari H. Singh, Ph.D.Phone: (301) 435-1310


Office of Science Policy andCommunications (OSPC)

SCIENCE POLICY BRANCH (SPB)

Science Education. In order to improve

science education in the area of drugabuse research (e.g., disciplines such as

neuroscience, psychology,

epidemiology), efforts are needed to

develop innovative methods forimproving knowledge of and generating

interest in science among school

children, the general public, and healthcare providers, including providers

involved in drug abuse treatment. These

might include but are not limited to:A. Development of methodologies to

present drug abuse and scienceinformation to particular groups, such

as kindergarten and elementary schoolstudents, African Americans,Hispanics, persons with disabilities and

health care providers.

B. Development of methodology to

transfer new knowledge and directionsof scientific growth to teachers,

curriculum developers and health care

providers.

C. Development of computer-basedlearning systems that allow students to

experience the scientific process.

D. Development of specific materials,

activities, or programs that promotescience education related to drug

abuse, such as exhibits, curriculummaterials, coloring books, videos,teacher education workshops,

partnership programs with scientistsand educators, or workshops for health

care providers.

E. Development of specific materials,

activities or programs that promote theteaching of scientific and research

ethics to middle and high schoolstudents.

Cathrine A. Sasek, Ph.D.(301) 443-6071


Division of Epidemiology, Services and

Prevention Research (DESPR)

A. Prevention Research Branch (PRB).The Prevention Research Branch(PRB) supports a program of research

in drug abuse and drug related HIVprevention to (1) examine the efficacy

and effectiveness of new andinnovative theory-based prevention


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approaches for drug abuse, drug-related HIV/AIDS and other associated

health risks, (2) determine thecognitive, social, emotional, biologicaland behavioral processes that account

for effectiveness of approaches, (3)clarify factors related to the effective

and efficient provision of prevention

services, and (4) develop and testmethodologies appropriate for studyingthese complex aspects of preventionscience.

Prevention Research. Rigorousscientific prevention research is

encouraged to study novel approachesto substance abuse prevention for use

at multiple levels of the socialenvironment including: the family,

schools, peer groups, community andfaith-based organizations, the

workplace, health care systems, etc.The purpose of this research is todetermine the efficacy and

effectiveness of novel programmaterials, training strategies, and

technologies developed to prevent theonset and progression of drug abuse

and drug-related HIV/AIDS infection.Materials and technologies may targeta single risk-level or may take a

comprehensive approachencompassing audiences at the

universal, selective, and/or indicated

levels. Universal interventions targetthe general population; selective targetsubgroups of the population withdefined risk factors for substance

abuse; indicated interventions targetindividuals who have detectable signs

or symptoms foreshadowing drugabuse and addiction, but who have not

met diagnostic criteria. NIDAencourages the development andtesting of innovative prevention

intervention technologies that are

sensitive and relevant to cultural andgender differences.

1. Laboratory studies of the

underlying mechanisms and effectsof various prevention approaches

such as persuasive communication(e.g., mass media and print media)

as they are affected by and affect

drug related cognition, emotion,motivation and behaviors.

2. Decomposition of preventionprograms to understand

components that account forprogram effectiveness.

3. Research on design features of

prevention curricula, materials, andapproaches that result in positiveoutcomes.

4. Training modules for programimplementers of research basedsubstance abuse prevention

programming strategies.

5. Prevention interventiondissemination technologies andmechanisms that integrate

research with practice; specifically

the transfer of drug abuseprevention information to decision-makers, funders, and practitioners.

6. Prevention services research onthe organization, financing,

management, delivery, andutilization of drug abuse prevention

programs.

7. Strategies for the integration of

proven prevention approaches intoexisting service delivery systems.

8. Studies that develop and assess

reliability and validity ofdevelopmentally appropriate self-report, physiological, andbiochemical measures for use in

prevention trials in a variety ofsettings and a variety of audiences.

9. Development of community needsassessment tools and services.

10. Drug abuse preventionmethodological research on

promising data collection, data

storage, data dissemination, andreporting techniques.

Larry A. Seitz, Ph.D.

(301) 402-1725

Email: [email protected]. Epidemiology Research Branch

(ERB). The ERB supports a research

program on drug abuse epidemiologythat includes (1) studies of trends and


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patterns of drug abuse and relatedconditions such as HIV/AIDS in the

general population and amongsubpopulations, (2) studies of causalmechanisms leading to onset,

escalation, maintenance, and cessationof drug abuse across stages of human

development, (3) studies of person

environment interactions, (4) studies ofbehavioral and social consequences ofdrug abuse, (5) bio-epidemiologicstudies including genetic epidemiology

studies, (6) methodological studies toimprove the design of epidemiologic

studies and to develop innovativestatistical approaches, including

modeling techniques.

1. Improvement of Reliability andValidity of Reporting of SensitiveData. The reliability and validity of

self-report of drug use and relatedbehaviors (e.g., HIV risk behavior)is a matter of great concern. Use of

new technologies for real time datacollection in ecological settings is

of great interest because thesetechnologies enable collection of

drug consumption data in context.Studies to improve methodologiesbased on variations of standard

survey protocols or computer-assisted self-interview (CASI) and

personal interview (CAPI) are also

encouraged.

2. Instrument Development. Easy-to-use assessment instruments are

needed to enhance epidemiologyresearch. Areas of interest includebut are not limited to:

a. Community Assessment. Thedevelopment of communitydiagnostic instruments forpsychometrically sound

assessment of community

characteristics is essential toimprove our understanding ofhow community factors affect

drug abuse and ensuingbehavioral and socialconsequences. Standardized

assessments of communitycharacteristics are needed to

better understand the fullimpact of drug use and to

develop targeted interventionsto specific community needs.

b. Assessment of PsychiatricComorbidity in CommunitySettings. Easy to use, reliable,and valid instruments areneeded to assess psychiatric

comorbidity in differentpopulations of drug abusers,

including adolescents andthose in community drug abuse

treatment settings.

c. Assessment Instruments toMeasure CNS FunctionRelated to Drug Abuse. Thedevelopment of age-appropriate assessmentinstruments to measure

behavioral and cognitive

function over the course ofdevelopment will contribute toour understanding of

vulnerability to drug abuse andfunctional impairment due todrug use.

Lynda Erinoff, Ph.D.

(301) 443- 6720

Email: [email protected]. Services Research Branch (SRB).

The SRB supports a program of

research on the effectiveness of drugabuse treatment with a focus on thequality, cost, access to, and cost-

effectiveness of care for drug abusedependence disorders. Primary

research foci include: (a) theeffectiveness and cost-benefits and

cost-effectiveness of drug abusetreatment, (b) factors affectingtreatment access, utilization, and health

and behavioral outcomes for definedpopulations, (c) the effects of

organization, financing, andmanagement of services on treatment

outcomes, (d) drug abuse servicedelivery systems and models, such ascontinuity of care, stages of change, or

service linkage and integration models,and (e) drug abuse treatment services

for HIV seropositive patients and forthose at risk of infection.

1. Drug Abuse Treatment EconomicResearch. This initiative will


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support research to design anddevelop data systems for financial

management and economicanalysis of treatment programs andlarger systems in new healthcare

settings and managed carenetworks. Managerial decision-

making requires the

implementation of sophisticateddata systems to facilitate routinebudgeting processes, allocation ofresources, performance

measurement, and pricingdecisions. The focus is on the

needs of managers within theorganization and managers outside

of the organization. Data systemdevelopment must be based onstandard cost behavior and profit

analysis. Data systems must be

designed with correct costconcepts (accounting andeconomic) in order to permit cost

and pricing decisions to bedeveloped for new treatmenttechnologies and management of

on going systems. In researchsettings, such an initiative is vital

for the assessment of newtechnologies developed for transfer

to practice.

William S. Cartwright, Ph.D.

(301) 443-4060

Email: [email protected]. Personnel Selection Technology

Research for Drug AbuseTreatment Clinics. NIDA would beinterested in supporting small

innovative research that developsand validates generic selectionsystems that could be adopted and

tailored for use by drug abusetreatment clinics. Like many small

businesses, drug abuse treatmentclinics have problems attracting

and retaining qualified personnel.Also like many small businesses,treatment clinics have limited

resources to apply to the recruitingand hiring of new and replacement

personnel. Though reliable dataare lacking, a great many clinic

directors complain of high annualstaff turnover rates. This has been

attributed anecdotally to poorquality of work life, low wages, low

skill levels, incompatibilities withthe clinics treatment philosophy,and the high stress of working with

drug abusers. Research has shownthat the application of standardized

selection methods designed to

maximize person-job fit can cost-effectively reduce staff turnover.Systematic methods such asbackground inventories, protocol-

driven interviews, aptitude tests,and credit checks have

demonstrated validity for improvingperson-job fit. Examples of

possible projects might includedevelopment of easy-to-understandguidance about legal

considerations in hiring practices,

software that transform job taskanalysis into selection criteria,interview protocols to standardize

applicant screening, tolls to helpimprove recruitment, and/or self-paced training for hiring officials or

interview panels to improvescreening reliability.

3. Customer Retention Technology.Premature disengagement from

drug abuse treatment participationis a common problem and ranges

from approximately 30 to 60%

based upon the clinic and modalitystudied. Past research has veryfrequently attributed dropping outof treatment to participant

characteristics (e.g., motivation,addiction severity, comorbidity)

and/or environmental factors (e.g.,social pressures, unemployment,

homelessness). Seldom has thedropout problem been studied inthe context of customer

satisfaction. That is, there is little

research looking at the causes ofdropping out of treatmentatt

2004 nida topics

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