Women and Sex/Gender Differences Research Program

April 2012
Lori Whitten, NIDA Notes Staff Writer

Since its inception, NIDA has sponsored research on issues related to women. Beginning with an early focus on the effects of drug use on pregnant women and the children they bear, the Institute soon expanded its interest to sponsor research into women’s specific addiction risk factors and treatment needs. When the HIV/AIDS epidemic emerged in the 1980s, NIDA responded with funding for projects on gender-specific risk factors for infection and on the impact of drug abuse on HIV transmission between mother and newborn and the subsequent health of both.

In 1995, NIDA formally established the Women and Sex/Gender Differences Research Program with the objective of achieving a comprehensive understanding of addiction and optimally effective prevention and treatment interventions for both men and women. The Program works with NIDA’s Divisions to integrate the study of male-female differences in drug and treatment responses into all areas of NIDA-sponsored research. “Without information on sex and gender effects, researchers may draw incorrect conclusions about the underlying causes of addiction and best ways to prevent and treat addiction in both men and women,” says Dr. Cora Lee Wetherington, the Program’s Research Coordinator.

Strategic and Dissemination Activities

Dr. Wetherington and Program Deputy Research Coordinator Dr. Samia Noursi lead the Women and Sex/Gender Differences Research Group (WGRG). This group regularly convenes scientists from throughout NIDA to discuss the state of scientific knowledge, new findings, and as yet unanswered questions. WGRG members draw on these exchanges to infuse issues of women and sex/gender differences into all types of Institute research, from animal models to intervention trials. For example, WGRG members helped plan NIDA’s recent research initiatives on gender differences in prescription drug abuse, the efficacy of addiction treatments, and substance abuse among members of the military and their families.

Functional magnetic resonance images show a cross-sectional view of three female and three male brains. The brains of the female smokers have substantially more white, yellow, and orange areas than those of males, indicating higher levels of activation after exposure to smoking cues.Heightened Brain Response to Cigarette Cues Among Women After exposure to cigarette cues, female smokers showed heightened activity in several brain regions—including areas of the reward pathway—compared with male smokers, Dr. Teresa Franklin and colleagues at the University of Pennsylvania have demonstrated. The top three functional magnetic resonance images show the locations where females have greater activity, and the lower three show the locations of heightened activity in males. The largest differences appear white/yellow, and more moderate differences appear orange.
Image courtesy of Teresa Franklin, Jason Gray, John Listerud, John Monterosso, Charles P. O’Brien, and Anna Rose Childress.

The WGRG also organizes and sponsors—often in collaboration with other groups—symposia, seminars, and Webinars to provide addiction researchers, clinicians, and program administrators with the latest information on the influence of sex and gender on drug abuse. Recent topics of these dissemination activities have included interventions to reduce smoking among pregnant women, HIV prevention among women who abuse drugs, and the potential impact of sex-related neurobiological differences on addiction.

To encourage young researchers to get involved in addiction research on sex and gender differences, the Program has established a dissertation award program for outstanding studies in this area and provides travel awards to the annual meeting of the College on Problems of Drug Dependence.

The Program has partnered with the National Institute on Alcohol Abuse and Alcoholism in issuing the funding opportunity announcement, “Women and Sex/Gender Differences in Drug and Alcohol Abuse/Dependence” (http:// The Program has long-standing collaborations with the National Institutes of Health (NIH) Office of Research on Women’s Health, with which NIDA cofunds three center grants and mentoring for junior faculty to develop research careers focusing on women and sex/gender differences in drug abuse.

Sex and Gender in the Clinic...

“Clinical studies that examine outcomes separately for men and women can help determine whether treatments have differential effectiveness or distinct side effects in the two genders,” says Dr. Wetherington. The Program works closely with NIDA’s Clinical Trials Network (CTN), helping investigators formulate hypotheses and design protocols that take into account sex- and gender-related differences in responses to treatment. CTN studies, which are conducted in community-based treatment facilities, have shown that gender-specific programs to teach substance-abusing men and women safe-sex skills outperform standard care in reducing risky behaviors (see “Intensive Interventions Reduce Risky Sexual Behaviors”).

The Program takes the lead in promoting NIDA clinical research on drug abuse among pregnant women and its effects on their children. The value of such studies is exemplified by recent findings that interventions that bridge prenatal care and help build parenting skills improve treatment outcomes for both mother and child (see “Home Visits by Nurses to Low-Income First-Time Mothers Yield Enduring Benefits”) and that treating addicted pregnant women with buprenorphine rather than methadone can lead to shorter hospital stays for their newborns and less need to give neonates methadone for opioid withdrawal.

Many Differences

NIDA research indicates that optimal treatment for all drug abusers must take into account male-female differences in:

  • Responses to drugs in some brain areas
  • Risk and protective factors for drug abuse
  • Reasons for abusing prescription drugs in young adulthood
  • Benefits obtained from certain treatments
  • Reasons for dropping out of treatment and relapsing
  • Outcomes affected by prenatal drug exposure

Among the Program’s clinical foci, the issue of sex-specific responses to medication interventions addresses a historically understudied area. For many years, researchers omitted women from clinical trials to avoid the difficult challenge of assessing possible effects of female hormones and menstrual cycles on the study results. This situation has eased since NIH mandated the inclusion of women in all NIH-funded clinical trials in the mid-1990s. NIDA-supported findings underline the importance of this mandate: We now know, for example, that women have a harder time quitting smoking than men and benefit less from nicotine replacement therapy.

...and in Basic Research

The Program promotes laboratory research to seek neurobiological explanations for differences in drug and treatment responses observed between men and women and to reveal differences between male and female animal behaviors that have potential relevance for people. Among potentially far-reaching findings in the latter line, recent studies have shown that female rats learn to self-administer several types of drugs of abuse more quickly than males, consume more of the drugs, and demonstrate greater reinforcement from them. “This animal model and human laboratory research can suggest prevention and treatment strategies that are gender-based or have gender-based components,” says Dr. Wetherington.

Although hormones are not the only reason a drug or medication might affect men and women differently, the question of hormonal influences on drug responses may be critical for the addiction field. “Scientists know that ovarian hormones influence neurotransmitters that are associated with addiction, and NIDA basic researchers have shown that these hormones affect drug self-administration, the motivational properties of drugs, and the neural processes underlying addiction. This is why it is important for NIDA’s research with animal models to include females and examine the role of ovarian hormones on outcomes,” Dr. Wetherington says.

The Program is hoping to take full advantage of the many powerful new research tools and techniques that are available for the identification and elucidation of gender differences. Dr. Wetherington says, “New imaging modalities, molecular biology, and genetics are making great contributions to our understanding of addiction. We need to infuse the study of sex differences in those and other fields.”

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