INHALANT ABUSE RESEARCH

NIH GUIDE, Volume 22, Number 39, October 29, 1993



PA NUMBER:  PA-94-006



P.T. 34



Keywords:

  Drugs/Drug Abuse 



National Institute on Drug Abuse



PURPOSE



This program announcement encompasses the broad research field of

inhalant abuse which has received little attention and has not been

adequately researched.  Prevalence data from both the National

Institute on Drug Abuse (NIDA) National Household and High School

Surveys have identified inhalant abuse as a significant problem that

shows little evidence of abatement and may still be increasing in

scope.  Based on the general information available and the portfolio

of grants supported by NIDA, this announcement identifies

deficiencies in our knowledge base in many areas of research that

need development.  Investigators from many scientific disciplines are

encouraged to apply either individually (e.g., as individual

projects) or collectively (e.g., as a program project).



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This program

announcement, Inhalant Abuse Research, is related to the priority

area of alcohol and other drugs.  Potential applicants may obtain a

copy of "Healthy People 2000" (Full Report:  Stock No.

017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)

through the Superintendent of Documents, Government Printing Office,

Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by foreign and domestic, for-profit and

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, research institutions, units of

State or local governments, and eligible agencies of the Federal

government.  Applications from minority individuals and women are

encouraged.  Foreign institutions are not eligible for First

Independent Research Support and Transition (FIRST) (R29) Awards.



MECHANISMS OF SUPPORT



Support mechanisms include:  research project grants (R01), small

grants (R03), FIRST Awards (R29), and program projects (P01).

Because the nature and scope of the research proposed in this program

announcement may vary, it is anticipated the size of an award will

vary also.  For details on a particular mechanism, contact the

program staff listed under INQUIRIES.



RESEARCH OBJECTIVES



The term "inhalant abuse" is used to describe a variety of drug abuse

behaviors that cannot be classified by any associated pharmacology or

toxicology, but only by the mode of administration.  Inhalants are

volatile substances that are primarily administered by inhalation,

used for altering one's mental status.  On this basis, several

subcategories can be established:  (a) industrial or household

solvents, including paint thinners or solvents, degreasers or

cleaning fluids, gasoline, and volatile substances in glues; (b) art

and office supply solvents including correction fluids and solvents

in magic markers; (c) gases (e.g., butane and chlorofluorocarbons)

used in household or commercial products, e.g., butane lighters,

whipping cream dispensers (nitrous oxide), electronic contact

cleaners (dusters) and refrigerant gases; (d) household aerosol

propellants in items such as paint, hairspray, cooking lubricant, and

fabric protector sprays; (e) medical anesthetic gases such as ether,

chloroform, halothane, and nitrous oxide; and (f) aliphatic nitrites.

Other inhaled substances not considered in this category include

tobacco, marijuana, heroin, and "crack."



The practice of sniffing, huffing, bagging, or inhaling to get high

describes various forms of inhalation abuse.  This area has been

reviewed recently (Inhalant Abuse:  A Volatile Research Agenda, NIDA

Monograph 129, 1992).  Prevalence of inhalant and other drug use is

chronicled in the National High School Senior and Household Surveys

(1991).  Both publications are available by request from the National

Clearinghouse for Alcohol and Drug Information, P.O. Box 2345,

Rockville, MD 20852, (800) 729-6686.



Research Areas of Interest



I.  Etiology



Research is needed to determine the bases for the initiation and

development of inhalant dependency and includes community-based and

longitudinal and cultural studies with matched controls.



Studies could focus on how such factors as lack of family support,

family violence, lack of role models, poor parental supervision,

parental drug use, breakdown of the extended family system,

association with different peer groups and the socio-economic status

affect initiation, continuation, escalation, and cessation of

inhalant use among individuals at risk of using drugs, particularly

minority youth.



Studies are encouraged that focus on cultural values and attitudes

toward inhalant use, acculturation related stress, or loss of

cultural identification of minority individuals, of the existence of

subcultures of inhalant use, crosscultural etiology (local, endemic

or worldwide), drug availability and distribution networks,

recreational and employment opportunities, negative social

sanctioning and attitudes within society, gangs, religion, and

empowerment on the use of inhalants should be considered.



Studies of the impact of psychological, developmental, and

psychopathological factors, influence of low self-esteem, depression,

aggressive behavior, coping styles, or the opposite factors that

establish resiliency and protection for those high-risk minority

children who do not abuse drugs such as inhalants are relevant.  Such

studies might lead to the early identification of those at risk of

inhalant use or identify motivating factors responsible for the

cessation of inhalant use.  Also important are studies on the role of

criminal activity (including deviance and rebelliousness) in inhalant

users, the etiological relationship between inhalant-using youth and

learning disabilities and the exploration of the distinct age

patterns displayed by solvent users.



There are associations between specific occupations or occupational

settings and inhalant abuse that need study.  Also, does alcohol and

lack of use of protective devices (e.g., respirators) in occupational

settings or other occupational parameters relate to workers' abuse of

volatile substances?



II.  Epidemiology



Studies are needed to provide a definitive understanding of the

patterns and prevalence of inhalant use among high-risk minority

youth, school dropouts, gang members, children of drug users, and

homeless youth.



These studies should focus on the emotional, physical, and economic

status of individuals, their families, and communities; the

interrelationship between inhalant abuse and violence; the dynamics

associated with different consequences relative to inhalant abuse;

identification of disease states related to inhalant exposure; bases

for endemic patterns of abuse and diminished use of various solvents;

and ethnographic studies of the users' values, beliefs, routines, and

consequences of their solvent-using behaviors relative to solvent

abuse.



III.  Prevention Intervention



Inhalant abuse intervention research scientifically approaches the

causes, onset, and progression of inhalant use in order to design,

develop, and test theory-based prevention interventions focused upon

the individual, family, peer group, and community (school, workplace,

neighborhood).  These studies may focus on identifying early

childhood behaviors and characteristics of high-risk inhalant abusers

such as attention deficit disorders, conduct disorders,

hyperactivity, and learning deficits.



Primary goals of intervention research are to develop a

scientifically sound knowledge base concerning the efficacy and

effectiveness of inhalant abuse prevention policies and programs, and

develop and test innovative intervention strategies.



IV.  Treatment



Treatment of inhalant abuse, especially solvent abuse, has not been

adequately studied.  Therefore, investigators should give increased

attention to improving existing therapeutic approaches or to

developing new strategies.  Studies should focus on treatment

designed specifically for adolescents, chemically dependent pregnant

women, high-risk individuals, individuals with co-occurring medical

and/or mental disorders, and those involved in criminal activities.

Investigators should scientifically evaluate counseling,

psychotherapy, family and group therapy, social skills training,

acupuncture and medication as approaches to the treatment of inhalant

abuse dependency and correlative medical consequences.



Outreach strategies, alone and in combination with extensive case

management, should be examined in terms of enlisting and maintaining

inhalant-dependent persons in treatment and rehabilitation programs.

Related research might also examine the form and extent to which

professional, political, economic, and administrative factors relate

to the accessibility and effectiveness of therapeutic programs and

supportive services that are already available.  Additionally,

research should be directed toward developing screening techniques,

biological (e.g., brainstem evoked responses) and other measures,

such as those based on self-report and diagnostic tools related to

criteria specific to inhalant abuse and dependency.  Other studies

should identify pre-existing and co-existing neurobiological,

psychosocial, and environmental factors that significantly impact on

treatment outcomes.



V.  Clinical and Laboratory



Several medical sequelae have been correlated with inhalant abuse,

including hearing loss, neurological degeneration, metabolic

acidosis, and loss of cerebellar function.  Further research needs to

evaluate the medical sequelae and neuropsychological/neuropsychiatric

consequences of inhalant use incorporating epidemiologic, clinical,

and natural history approaches; evaluate associated learning

difficulties as both a cause and a consequence of inhalant use;

develop improved methods of detecting and differentiating different

types of inhalant use, especially long-term use, through laboratory

and self-report methods; develop improved methods of detecting and

treating medical conditions associated with inhalant abuse; clarify

the role of psychiatric disorders as both a cause and a consequence

of inhalant abuse, and improve the methods of evaluating the

physiological effects of inhalants in human subjects, such as more

sensitive neuropsychological batteries and related techniques that

allow differentiating the effects of inhalants from other drugs and

conditions.



There are a wide variety of substances in various products that are

being abused.  Animal studies of these substances should be

correlated with human studies identifying various clinical syndromes

including:  measures of acute and long-term irreversible neurological

effects; correlating the pharmacodynamics with the distribution and

bioavailability of abused solvents and their metabolites in animals

and humans, multi-solvent interaction, and of in utero exposure

(fetal toxicity), which mimics conditions of human pregnancy.

Experimental animal and prospective human studies should also include

the evaluation of lethal toxicity (especially cardiac sensitization),

neurotoxicity (e.g. seizures) and other neurological measures (e.g.,

brainstem evoked responses or BAER's) combined with neuroimaging

techniques (e.g., PET, SPECT, and EMIT) and morphological (human

post-mortem tissues analyses) and determine the physical and/or

psychological dependence of various inhaled substances.  Etiologic

studies may draw on previous cohorts and use those controls who

subsequently become inhalant abusers.



Studies of interest also include animal and human behavioral

experiments of inhalant exposure on learning and performance,

including those identifying associated neurologic systems and basic

mechanisms of action underlying these actions.  This includes

measures of cognitive and neurological determinants that initiate or

moderate long-term use of inhalants in humans, behavioral indices of

both acute and chronic inhalant exposure, (e.g., operant behavioral,

learning versus performance, and avoidance conditioning [and

learning/discrimination or memory] tasks), drug-discrimination

studies to compare subjective (user experienced) effects and brain

electrical self-stimulation.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements will be required to include minorities and

women in study populations so that research findings can be of

benefit to all persons at risk of the disease, disorder or condition

under study; special emphasis should be placed on the need for

inclusion of minorities and women in studies of diseases, disorders

and conditions which disproportionately affect them.  This policy is

intended to apply to males and females of all ages.  If women or

minorities are excluded or inadequately represented in clinical

research, particularly in proposed population-based studies, a clear

compelling rationale should be provided.



The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of

the study.  This information should be included in the form PHS 398

in Sections 1-4 of the Research Plan AND summarized in Section 5,

Human Subjects.



Applicants are urged to assess carefully the feasibility of including

the broadest possible representation of minority groups.  However,

NIH recognizes that it may not be feasible or appropriate in all

research projects to include representation of the full array of

United States racial/ethnic minority populations (i.e., Native

Americans (including American Indians or Alaskan Natives),

Asian/Pacific Islanders, Blacks, Hispanics).



The rationale for studies on single minority population groups should

be provided.



For the purpose of this policy, clinical research includes human

biomedical and behavioral studies of etiology, epidemiology,

prevention (and preventive strategies), diagnosis, or treatment of

diseases, disorders or conditions, including but not limited to

clinical trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.



For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the application will be returned.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and will be

reflected in assigning the priority score to the application.



All applications for clinical research submitted to NIH are required

to address these policies.  NIH funding components will not award

grants or cooperative agreements that do not comply with these

policies.



APPLICATION PROCEDURES



Applications are to be submitted on the grant application form PHS

398 (rev. 9/91) and will be accepted at the standard application

deadlines as indicated in the application kit.  The receipt dates for

applications for AIDS-related research are found in the PHS 398 (rev.

9/91) instructions.



Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grant

Inquiries, Division of Research Grants, National Institutes of

Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone

(301) 435-0714.  The title and number of the announcement must be

typed in Section 2a on the face page of the application.



The completed original application and five legible copies  must be

sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications will be assigned on the basis of established Public

Health Service referral guidelines.  Applications will be reviewed

for scientific and technical merit by initial review groups in

accordance with the standard NIH peer review procedures.  Following

the scientific/ technical review, the applications will receive a

second-level review by the appropriate national advisory council.

Small grant applications (R03) do not receive a second-level review.



AWARD CRITERIA



Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding

decisions:



o  Quality of proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement



INQUIRIES



The opportunity to clarify any issues or questions from potential

applicants is encouraged.



Direct inquiries regarding programmatic issues to:



Charles Sharp, Ph.D

Division of Basic Research

National Institute on Drug Abuse

Parklawn Building, Room 10A-31

5600 Fishers Lane

Rockville, MD  20857

Telephone:  (301) 443-1887



Direct inquiries regarding fiscal matters to:



Gary Fleming, J.D., M.A.

Grants Management Branch

National Institute on Drug Abuse

5600 Fishers Lane, Room 8A-55

Rockville, MD  20857

Telephone:  (301) 443-6710



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance No. 93.279.  Awards are made under authorization of the

Public Health Service Act Section 301 (42 USC 241) and administered

under PHS grants policies and Federal Regulations at Title 42 CFR

Part 52, "Grants for Research Projects,"  Title 45 CFR part 74 & 92,

"Administration of Grants," and 45 CFR Part 46, "Protection of Human

Subjects."  Title 42 CFR Part 2 "Confidentiality of Alcohol and Drug

Abuse Patient Records" may also be applicable to these awards.  This

program is not subject to the intergovernmental review requirements

of Executive Order 12372 or Health Systems Agency review.  Sections

of the Code of Federal Regulations are available in booklet form from

the U.S. Government Printing Office.  Awards must be administered in

accordance with the PHS Grants Policy Statement (rev 10/90) available

from most offices of sponsored research.



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