ETIOLOGY, CONSEQUENCES, AND BEHAVIORAL PHARMACOLOGY OF FEMALE DRUGABUSE



NIH GUIDE, Volume 22, Number 9, March 5, 1993



PA NUMBER:  PA-93-059



P.T. 34



Keywords:



National Institute on Drug Abuse



PURPOSE



This program announcement seeks to stimulate research on (a) the

etiology and consequences of drug abuse by women of all ages and

reproductive status and (b) gender differences in the behavioral

effects of abused drugs.  Studies on the etiology, natural history,

and consequences of drug abuse unique to women include health risk,

psychosocial, psychiatric, physiological, and neuroendocrine factors

and clinical, social, economic, and legal issues related to the

multiple roles and status of women (i.e., the role of drug use in

female sexual activity, pregnancy, parenting, transmission of AIDS,

stress and coping strategies, self identity and self esteem, health

beliefs and practices and methods to reach, identify, and predict at

risk individuals).  Behavioral pharmacology studies include animal

studies and human laboratory studies on all phases of drug abuse

(acquisition, maintenance, withdrawal, and relapse) and are to

examine gender differences in the behavioral effects of abused drugs.



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, Etiology, Consequences, and Behavioral Pharmacology of

Female Drug Abuse, is related to the priority area of alcohol and

other drug abuse.  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, units of State and local

governments, and eligible agencies of the Federal government.

Applicants from minority individuals and women are encouraged.

Foreign institutions are not eligible for First Independent Research

Support and Transition (FIRST) awards (R29).



MECHANISM OF SUPPORT



Support mechanisms include research projects (RO1), small grants

(RO3), and FIRST awards (R29).  Because the nature and scope of the

research proposed in response to this program announcement may vary,

it is anticipated that the size of an award will vary also.



RESEARCH OBJECTIVES



Studies are needed on (a) the etiology, nature, concomitants, and

consequences of drug abuse by women of all ages and reproductive

status and (b) basic research involving laboratory studies on gender

differences in the behavioral effects of abused drugs.  One goal is

to seek a scientific basis for decision making regarding drug abuse

and women in recognition of the social, economic, political, marital,

familial, and caretaker roles of women and their special

vulnerabilities with regard to drug abuse.  Another goal is to bring

meaning to the efforts to assess gender differences in research on

the behavioral effects of drug abuse.



Etiology and Consequences of Drug Abuse Among Women:  Conceptual

models and theoretical constructs in drug abuse research based on

research with male subjects do not recognize factors unique to

females and the multiple etiologies, vulnerabilities, and special

problems of women.  Although the number of male drug abusers and

addicts exceeds the identified number of female drug abusers and

addicts, the clinical picture and consequences of drug abuse by women

are more severe although little is known about why this occurs or how

to intervene.  The changing role of women in society creates a need

to track how this may affect present and future substance abuse

patterns.



Existing studies of gender differences in drug metabolism, endocrine

functioning, and reproductive biology and the natural history of drug

abuse among subgroups of women--women with drug abusing partners,

adult children of alcoholics and drug addicts, prostitutes, women

having undergone traumatic life events--highlight the urgency of

research in this area.  Sex hormones interact at critical life stages

to produce profound differences.  Metabolites of illicit drugs are

differentially stored and recirculated based on complex factors

including age, gender, and physiologic reactions to stress.  Research

questions need to address clinically and socially relevant problems

and follow the axiom of picking the most appropriate design, units of

measure, and levels of analysis which fit the research question.



In depth descriptive and ethnographic studies are needed to address

fundamental issues on which future work can be based.  Because of the

realities of women in hidden, underserved populations, a combination

of insight building studies and meticulous longitudinal studies need

to be initiated.  Studies also need to consider possible

vulnerabilities due to drug effects on the female's developing

central nervous system, metabolism, or endocrine functioning and

their psychosocial development.  Studies are needed which have

promise of producing clinically significant information and tools for

risk assessment, intervention, treatment, and prevention strategies.



Areas of Special Interest:  Drugs of abuse include illicit drugs and

alcohol, tobacco, and medications within the context of polydrug

abuse.  Areas include, but are not limited to, studies of the natural

history, etiology, consequences, concomitants, incidence and

prevalence of drug use, abuse, dependence, and addiction among women,

specifically:



o  The role of drug use in female sexual activity, pregnancy,

parenting, and high risk sexual behaviors;



o  Differences in drugs of abuse, patterns of abuse, routes of

administration, different physiologic and therapeutic responses, and

abuse of prescription drugs by females;



o  The role of factors which increase risk for early onset and

severity of drug abuse, such as stress and coping strategies, self

identity and self esteem, sexual identity, psychosexual and social

role, psychopathology, socioeconomics, metabolic and neuroendocrine

functioning, reproductive and health status, health beliefs and

practices, drug abuse by significant others, victimization,

interrelationships between drug abuse and problem behaviors

(delinquency, prostitution, high risk sexual activity, unwanted

pregnancy);



o  Differential consequences of female drug abuse: morbidity, co-

morbidity; psychological, social, economic, health and reproductive

outcomes mediated by immune, endocrine, and other systems

(differential physiologic, neurologic, psychiatric, psychologic,

metabolic factors), and the clinical neuroscience interface with

behavior;



o  Etiology of drug abuse among subgroups of women;



o  Special factors affecting subgroups of women (incarcerated,

homeless, victims of violence, single head of household);



o  Impact of age at onset in developing drug and other disorders;



o  Victimization, rape, trauma, child abuse and neglect, and post

traumatic stress disorder with women as victim or perpetrator;



o  Natural history of transmission of HIV among drug abusing women,

especially women in minority and homeless populations;



o  Intergenerational studies of factors that transmit risk for drug

abuse including role of females who model behaviors for daughters and

influence how sons will relate to females;



o  Legal, health, and social policy issues;



o  Barriers to identification, diagnosis and treatment for women;



o  Incidence and prevalence of drug abuse among women and methods to

reach, identify, and predict individuals at risk for drug abuse and

misuse of prescriptive drugs;



o  Animal models to look at factors which are difficult or can not be

examined in human studies.



Laboratory Studies on Gender Differences in the Behavioral Effects of

Abused Drugs:  The PHS has explicit requirements for the inclusion of

women in clinical research grants.  This requirement grew out of

concern that research findings benefit both men and women.  The

requirement, however, does not demand inclusion of an adequate sample

of both genders so that separate conclusions can be drawn about men

and women.  Recent studies, however, showing gender differences in

the behavioral responses to abused drugs indicate the need for

further research in this area to achieve the objective of obtaining

research findings that are of benefit to both men and women.



Converging evidence from human and animal research stresses the need

for further basic laboratory research on gender differences in the

behavioral responses to abused drugs.  Preliminary data suggesting

that women may more rapidly proceed to addiction after casual drug

use than men, as well as evidence that effects of marijuana and

alcohol use in women is associated with the menstrual cycle, raise

questions about possible fundamental gender differences in the

reinforcing and stimulus properties of abused drugs.  Such

differences have been reported in animal studies with rodents.  On

several measures of stimulant-induced activity females exhibit more

responsiveness than males, and this responsiveness varies with the

estrus cycle.  Further, gender differences in self-administration of

cocaine have been reported.  When cocaine infusions were made

contingent upon increasingly higher numbers of bar presses, female

rats made substantially more presses than males and their level of

cocaine self-administration varied as function of the estrus cycle.



Research findings from laboratory studies on gender differences in

the behavioral responses to abused drugs should have implications for

the development of prevention, intervention, and treatment procedures

that are gender specific.  The high rate of drug use by women of

child-bearing age, thus potential prenatal drug exposure, underscores

the importance of this research.



Areas of Special Interest:  This announcement seeks to stimulate

behavioral pharmacology studies, in humans and animals, on gender

differences in the behavioral response to abused drugs.  Animal

studies focusing on all phases of drug abuse--acquisition,

maintenance, withdrawal, and relapse--are needed.  Within these

phases, studies of gender differences in (a) reinforcing and stimulus

properties of abused drugs, (b) behavioral and pharmacotherapeutic

interventions, and (c) behavioral history variables that may modulate

gender differences are of particular interest.  The existing

literature on the effects of gonadal hormones on learning and memory

and on neurotransmitter systems should serve to guide research in

these areas, where applicable.  Human laboratory studies examining

gender differences in the behavioral effects of abused drugs in non-

use and low-use subjects, as well as subjects who are in maintenance,

withdrawal, and relapse phases of drug abuse are needed.  Study of a

variety of factors that may modulate gender differences is

encouraged, including (a) hormonal and other biologic factors, (b)

behavioral history variables, such as dieting and drug use pattern,

(c) family history of drug abuse.



STUDY POPULATIONS



NIH POLICY CONCERNING INCLUSION OF WOMEN AND MINORITIES AS SUBJECTS

IN RESEARCH



Applications for grants and cooperative agreements that involve human

subjects are required to include minorities and both genders 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 including

minorities and women in studies of disease, disorders and conditions

which disproportionately affect them.  Although the applicability of

women to this program announcement is obvious, the requirement to

address minorities must be addressed.  If minorities are not included

in the study populations for clinical studies, a specific

justification for this exclusion must be provided.  Applications

without such documentation will not be accepted for review.



AIDS IRB Guidelines



Applicants are advised to obtain a copy of the "Guidance for

Institutional Review Boards for AIDS Studies (December 16, 1984)"

from the Office for Protection from Research Risks (OPRR), Building

31, Room 4B09, National Institutes of Health, Bethesda, MD 20892

(telephone: 301/496-7005).  This office may be consulted on how to

deal with difficult human subjects protection issues in AIDS

research.  Guidelines emphasize special considerations which must be

taken into account in AIDS research and stipulate important

protection that must be considered in design of AIDS research

projects, including the requirement that subjects be informed of the

result of AIDS antibody testing, if any such testing is done.



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 indicated in the application kit.  Receipt dates for

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

instructions.



Application kits are available at most institutional business offices

or offices of sponsored research and may be obtained from the Office

of Grants Inquiries, Division of Research Grants, National Institutes

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

301/496-7441).  The title and number of this announcement must be

typed in Item 2a on the face page of the application form PHS 398.



FIRST award applications must include at least three sealed letters

of reference attached to the face page of the original application.

FIRST award applications submitted without the required number of

reference letters will be considered incomplete and will be returned

without review.



The completed original and five legible copies of the application

form PHS 398 must be sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



The Division of Research Grants, NIH, serves as a central point for

receipt of applications.  Applications will be assigned in accordance

with established PHS referral guidelines.  Applications will be

reviewed by an initial review group (IRG) for scientific and

technical merit in accordance with the standard NIH review

procedures.



AWARD CRITERIA



Applications recommended for further consideration will compete for

available funds with all other applications assigned to the that

Institute.  The following will be considered in making funding

decisions:



o  Quality of the proposed project as determined by peer review;

o  Availability of funds; and

o  Program balance among research areas of the announcement.



INQUIRIES



Written and telephone inquiries to clarify any issues or questions

from potential applicants is welcome.



Direct inquiries regarding programmatic issues to:



Coryl Jones, Ph.D.

Division of Epidemiology and Prevention Research

National Institute on Drug Abuse

Rockwall II, Suite 615

Rockville, MD  20857

Telephone:  (301) 443-2974



Cora Lee Wetherington, Ph.D.

Division of Basic Research

National Institute on Drug Abuse

Parklawn Building, Room 10A20

Rockville, MD  20857

Telephone:  (301) 443-1263



Direct inquiries regarding fiscal matters to:



Mrs. Shirley A. Denney

Grants Management Branch

National Institute on Drug Abuse

Parklawn Building, 8A54

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 Public

Health Service Act, Sections 301 and 405 (42 USC 241 and 284). Title

42 Code of Federal Regulations (CFR) Part 52, "Grants for Research

Projects," Title 45 CFR Part 74, "Administration of Grants," and 45

CFR Part 92 are applicable to these awards.  Grants must be

administered in accordance with the PHS Grants Policy Statement,

(rev. 10/90).  This program is not subject to intergovernmental

review requirements of Executive Order 12372 or Health Systems Agency

review.



.

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