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Research Directions

and Opportunities

Richard A. Millstein

INTRODUCTION

The major focus of all the topics presented at this conference can be

subsumed under the general rubric of the demise of male-only research.

Future research cannot neglect females as it has in the past, and despite

the wealth of information presented during this conference, and some

promising findings, unfortunately, there still are more research gaps than

findings. Research that has a male-only approach cannot continue.

And it cannot be assumed that the results from research based exclusively on male subjects can be extrapolated confidently and generalized

safely to females. The U.S. Public Health Service guidelines on the inclusion of women and minorities in research are an important step in

redressing past decades of research that was predominantly male-focused.

The question is how these guidelines will be implemented in the future.

The National Institute on Drug Abuse (NIDA) is entering a new

era. NIDA’s 20th anniversary in 1994 provided the opportunity to look

not only at accomplishments but also at research gaps and goals and priorities for the future. NIDA has a long history of studying women and

sex differences; however, most of these studies have been among pregnant women and their offspring. Now it is necessary to look at females

as independent individuals, not just in their roles as mothers.

In recent years, NIDA has taken a number of important steps in an

attempt to fill the gaps in drug abuse-related women’s health issues. For

example, Dr. Loretta Finnegan was enlisted to serve as the senior adviser

on women’s health and research issues and to head the Women’s Health

Issues Group. The Women’s Advisory Committee was also established,

comprising representatives from each of the Institute’s major organizational components. In June 1993 a technical review on drug abuse and

HIV infection and their effects on women and children was conducted.

Also that year, two program announcements were issued seeking applications for research directly focused on women in two areas: first, the etiology, consequences, and behavioral pharmacology of female drug abuse,
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and second, drug abuse treatment for women of childbearing age and

their children. In June 1994 a technical review was conducted on

methodological issues involving the etiology and consequences of drug

abuse among women. In addition, some AIDS program announcements

have focused indirectly on women. These include notification of partners of HIV-infected drug users and strategies to reduce high-risk sexual

practices among drug abusers.

NIDA has released videos, NIDA Capsules, and brochures on the

subject of women’s health. In addition, dozens of NIDA-funded grants

have been awarded that have focused on women’s issues and sex differences. In fact, most of the presenters at this conference have been or are

NIDA grantees.

Although the activities NIDA has instituted are an important beginning, much remains to be done, and help is needed in two specific

ways. First, research on women and addiction must include biological

and behavioral sex-related differences and the effect of drug abuse prevention and treatment on women. NIDA wants and needs to receive

grant applications from all areas of research that can address women

and sex differences.

Second is the need to know what the research agenda should be.

The feedback and recommendations of those attending this conference

present an opportunity to determine that agenda. Research and clinical

practice are a two-way street. Clinicians and practitioners can enhance

the effectiveness of their services by using state-of-the-science practices

identified through research, and research professionals benefit from the

clinical judgment, wisdom, and insights of clinicians and practitioners

because such inclusion ensures that the research addresses clinical

concerns.

INVESTIGATIONAL AREAS

Conference participants identified several areas of investigation.

In epidemiology, research should be conducted on the role of sex differences and women’s vulnerability to drug use, the progression from initial

drug use to abuse and dependence, and the implications of sex differences for prevention and treatment approaches and strategies.

Replication of the initial findings of intergenerational transmission

of smoking behaviors from women who smoke during pregnancy to their
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female offspring (Kandel et al., this volume) must be accomplished.

These findings hold promise related to dopamine system regulation and

drug use. At the same time, it is necessary to avoid the too-common

practice of placing blame on women for their behaviors and their

pregnancy outcomes.

A caveat heard in most discussions of female drug abusers, whether

in reference to epidemiology, treatment, or prevention, is that women

constitute a heterogenous group of people; different strategies must be

used for different women and at different times in their lives. There is

no “one size fits all” in terms of prevention, treatment, etiology, or any

research area.

Another major research gap relates to the lack of information about

minority women, lesbians, and bisexual women. This deficiency is compounded by the fact that when information exists on so-called minority

women, too often the data are aggregated without attention to subgroups; for example, the term “Latinas” is used without regard to whether

women are Puerto Rican, Mexican-American, or Cuban by heritage.

Biological and behavioral mechanisms that need study include

cocaine’s effect on reproductive function, the effect of the estrous cycle

on cocaine self-administration, sex differences in response to serotonergic neurotransmission, and sex-specific considerations in the use of

psychoactive medications.

In the fields of etiology and prevention, more information is needed

about sex differences and child and adolescent precursors of drug abuse,

personality pathways that lead to drug use and progression to abuse and

dependence, protective factors, and resiliency and what constitutes invulnerability, as well as how to prevent drug use and related adverse

health and medical consequences.

Rates of anxiety and depressive disorders, considered precursors to

drug use and dependence, are reported to be higher for women than for

men (Moras, this volume). Such findings demand greater attention not

only by NIDA but also by its prevention and treatment partners so that

better treatment of anxiety and affective disorders can be offered and

drug dependence can be delayed or prevented.

Prevention and treatment programs must be designed to address the

specific research-based risk factors in women, such as sexual and other

childhood abuse and posttraumatic stress disorder. Research should
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examine the relationship between victimization and drug abuse among

women and whether partner violence is a consequence of drug use.

Many of these research issues relate to intergenerational models of

violence and alcohol and other drug problems and go beyond drug

abuse research, treatment, and prevention.

SEX DIFFERENCES

Information presented at this conference addressed treatmentrelevant sex differences; barriers, including legal barriers; fears about losing child custody; the need for comprehensive services—not just drug

abuse services but also health care services, child care services, and

perinatal programs; prenatal care; the need for vocational education;

housing; raising low self-esteem; and overcoming feelings of worthlessness, hopelessness, and helplessness and, therefore, the need for counseling and treatment for depression. There have been reports of different

rates of recruitment and retention for men and women seeking drug

treatment, and what these differences predict and portend, particularly

in relation to AIDS.

Research on sex differences relevant to treatment suggests that

women and men may respond differently to some treatments. These

differences emphasize the need for (1) comprehensive services,

(2) attention to the effects of violence, (3) recognition of the effects

of exposure to victimization and stress, and (4) health services, including

mental health and social services and case management. Male-oriented

and -dominated treatment programs may constitute poor or inappropriate treatment for females, even if they result in successful treatment

outcomes for males.

Women are reported to be less likely to accept random study assignments (Wallen, this volume); this refusal has tremendous implications

for research, recruitment of individuals, and the interpretation of data.

Females are less likely to do well in male-oriented, male-dominated,

male-theory-based programs. In addition, information is needed about

the components necessary for parental skills training and family therapy.

AIDS

AIDS and its epidemiology constitute another area of critical need

for more research related to women. Drug abuse by women is the vector
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for AIDS much more often than it is for men. Data as of September

1993 (Centers for Disease Control and Prevention 1993) indicate that

51 percent of AIDS cases in men resulted from men having sexual relations with men; for women, 46 percent of the cases resulted from women

being injection drug users (IDUs), and another 38 percent were attributable to heterosexual sex. Of this 38 percent, more than half the cases

were the result of heterosexual sex with IDUs (Selwyn, this volume).

The lack of epidemiological data about lesbians has implications for

AIDS epidemiology and therefore prevention and treatment.

Risk factors for HIV infection are different for women. For example,

among crack users, the adjusted odds ratio of acquiring HIV infection

for a male is 2.8-fold; but for a female, it is 4.7-fold. Female prostitutes

have 4.6 times the odds of being infected with HIV compared with men

who frequent prostitutes, who have 1.5 times the odds of being infected.

There is a need for research to investigate the possible mechanisms that

can explain these differences and, from this information, identify interventions that can prevent this outcome.

In the median survival time from AIDS diagnosis to death, women

die sooner than men, and some of the hypotheses and the implications of

this fact are startling, striking, and sad. There is a need to know whether

women present later than men, and if so, the reasons for and the implications of this behavior. In addition, women’s barriers to entry and treatment need to be better understood, as well as why women are underscreened for HIV infection and substance abuse compared with men

and what good medical practice is where women are concerned.

Another question relates to the implications of the AIDS definition,

now broadened by the Centers for Disease Control and Prevention to

include women with HIV infection who have cervical cancer (Centers

for Disease Control 1992; Selwyn, this volume). There is a need to determine whether that definitional change alone will affect the numbers

and how they are perceived.

AZT is offered to men more frequently than to women. The implications of this practice, particularly given the findings of a study on AZT

and transmission of HIV infection from mothers to newborns (Selwyn,

this volume), are potentially profound. In the control group, 25.5 percent of the women gave birth to infants with HIV infection, whereas the

rate was only 8.3 percent in mothers who had taken AZT. The study was

terminated early because of these results, but there is still a need to know
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whether more women are being given access to AZT and what changes

in practice have been made because of that study. Community alerts are

needed about this new information and this medication should be incorporated into our treatment and demonstration programs.

NIDA’s health services research agenda must be broadened to include

prevention as well as treatment, and treatment should include not only

drug abuse treatment but also AIDS treatment and primary care treatment. Research should address the issues of HIV and AIDS detection,

access to care, engagement into prevention or treatment, and utilization

of services, as well as questions related to specific subgroups of women,

such as women of color, lesbians, and bisexual women.

Conference participants identified the need to develop different care

models as well as integrated approaches linking health care, drug treatment, and HIV services. Also highlighted were other consequences

of drug abuse in the wake of HIV infection, AIDS, and drug abuse, including other sexually transmitted diseases, tuberculosis, and hepatitis.

There is a known association of alcoholism with mental health

problems, poor pregnancy outcomes, and adverse social and behavioral

consequences on coping and self-esteem. Also known is the role of social

supports as protection against drug abuse, high-risk sexual behaviors,

and psychiatric sequelae. The importance of the context in which people

live has been stressed: social, cultural, and economic factors; sex-related

issues; factors of race, ethnicity, and sexual orientation; program philosophy; the effects of racism and internalized racism; and the effects of

societal violence, partner violence, and living in a community where

violence pervades daily life.

Conference presenters also highlighted the need to focus on individuals’ strengths, not only on their deficits, and the need to look at genetic,

environmental, social, and cultural factors and combinations and aggregations of these factors. Biological and behavioral approaches and the implications for intervention for outreach also were identified for further

study.

TERMINOLOGY

Presenters emphasized the lack of clear-cut definitions. For example,

what are licit and illicit drugs? For minors, it must be remembered that

alcohol and tobacco are illicit drugs.
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Why is Congress not convinced that drug abuse is a priority in terms

of funding? Perhaps the answer to some extent lies in the lack of measures of outcomes. And what are the goals? What are seen as “good” outcomes? Must drug-free status be demanded, or can reductions in use and

harmful consequences be accepted as indicators of the success of treatment?

In reference to drug abuse, the term “relapse” is used. Professionals

in other health disorders and diseases speak about the “recurrences”

or “perturbations” expected of chronic disorders. Drug abuse can be

compared with hypertension and diabetes because they also are chronic

disorders characterized by poor patient compliance with diet, medication, and behavior change. But with hypertension and diabetes, relapse

is not mentioned; the terms used are “expected and normal recurrences.”

There is a lesson to be learned—if we are listening and attentive.

INSTITUTIONAL RESPONSIBILITY

People should have access to treatment even if they are not totally

abstinent. But acceptance of this fact requires educating Congress, the

Administration, medical doctors, the academic community, the media,

the public, and practitioners in the treatment community.

On the issue of including women and pregnant women in clinical

trials, there has been discussion about institutional review boards. But

the issue was not pursued in terms of what that inclusion means for finding the efficacy of candidate medications in nonpregnant women before

the medications are administered, what it means about the paternalism

that has existed for so long, and what it means in relation to the lack

of empowerment of women to make their own decisions about whether

they should be included as research subjects.

Whether the proliferation of agencies with drug abuse programs

is good has not been decided; it can be seen as fragmentation. For

example, NIDA deals with research; the Center for Substance Abuse

Prevention deals with prevention; the Center for Substance Abuse

Treatment deals with treatment; and individual States deal with the

direct delivery of treatment. NIDA sees its training role primarily in

research training, looking to the Substance Abuse and Mental Health

Services Administration (SAMHSA) and the Health Resources and

Services Administration for clinical training.
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NIDA, the National Cancer Institute, the National Heart, Lung,

and Blood Institute, and the Centers for Disease Control and Prevention

all have programs that address smoking. For children, there are programs within NIDA, SAMHSA, the National Institute of Child Health

and Human Development, and the Administration on Children, Youth,

and Families. To address violence and posttraumatic stress disorder,

anxiety, and affective disorders, there are programs within the National

Institute of Mental Health; for alcohol abuse and alcoholism, there are

programs in the National Institute on Alcohol Abuse and Alcoholism

and the Indian Health Service.

RESEARCH NEEDS

• Initiatives and collaborations with multiple interactions and partnerships. Although many organizations are involved, none of

them has taken ultimate responsibility. Everyone—inside and

outside Government—must recommit to focusing on individuals

and on restoring lives—productive, healthy lives of promise for

the next generation.

• More information about research dissemination and application

models that are effective in getting research-based information

out, applied, adopted, adapted, and used in clinical practice.

Much more information is needed about effective communication

and education.

• In addition to more research on women and women’s health,

more female researchers, including women of color and women

of all sexual orientations.

This list is not an exhaustive one, but it does present some research

needs, opportunities, and directions and the beginnings of a structural

framework for a program that will ultimately enable the drug abuse field

to better address and fulfill the long-neglected needs of women’s health.

REFERENCES

Centers for Disease Control. 1993 revised classification system for HIV

infection and expanded surveillance case definition for AIDS among

adolescents and adults. MMWR Morb Mortal Wkly Rep 41(RR-17):1-19,

1992.
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Centers for Disease Control and Prevention. HIV/AIDS Surveillance Rep 5(3):

7-8, 1993.

AUTHOR

Richard A. Millstein

Deputy Director

National Institute on Drug Abuse

5600 Fishers Lane, Room 10-05

Rockville, MD 20857

(301) 443-6480 (Tel)

(301) 443-9127 (Fax)

millstein@nih.gov (E-mail)