NIDA Research Priorities and Highlights
Role of Research
Women's Health and Gender Differences
Historically, in drug use research, as in other fields of public health research, test subjects have been almost exclusively male; as a result, little data have been available on the specific problems and issues concerning the effects of drug use on women. In recent years, however, NIDA has vigorously promoted drug use research focusing on the study of women and gender differences, and such research is now supported in all of NIDA's programmatic branches. Data from NIDA-supported laboratory, field, and clinical research are beginning to show gender differences in virtually all areas of drug research, including research on biological factors in drug use, the antecedents and consequences of drug use and abuse, and prevention and treatment. Some of the findings, emerging in the past few years, are described below.
Gender Differences in the Impact and Consequences of Drug Use
There is growing evidence that the effects of drug use and addiction do not always affect men and women in the same manner, and the rate of any drug use among men is nearly twice that of women (8.1 percent vs. 4.2 percent). Data also indicate that for several illicit drugs, women may proceed more rapidly to drug dependence than do men, which may have to do with the way the body responds to drugs.
Preliminary data from several studies using varying clinical end points are beginning to suggest that drugs of abuse may produce biologic impairment in males different from that in females. In a study of cerebral perfusion abnormalities in dependent cocaine users, for example, males were far more likely than females to exhibit abnormalities, perhaps because of a protective role of estrogen.  In addition, a magnetic resonance spectroscopy study of chronic cocaine users found that in the white matter of the brain, males had elevations in three of five naturally occurring metabolites, whereas female subjects had no elevations. 
A study of cocaine users found that male occasional cocaine users achieved significantly faster peak plasma cocaine levels after snorting cocaine than did women. Men also reported a greater number of intense effects. However, heart rates did not differ between males and females despite differences in peak plasma levels between genders. This suggests that the female cardiovascular system may be more sensitive than that of males to cocaine's effects. 
A study of neuropsychological functioning in cocaine abuse also points to a possible protective factor with regard to women. In a study of the effects of chronic cocaine use following sustained abstinence, both males and females exhibited impairment on measures of attention-concentration, memory, and academic achievement. Visual-spatial, motor, language, and executive functioning measures were less consistently impaired among females. Interestingly, although the female subjects had a substantially greater exposure to cocaine, they were no more impaired than the men on neuropsychological measures. 
Two recent studies dealing with the genetics of cigarette smoking have revealed interesting gender differences. The first study demonstrates a role for genetically variable nicotine metabolism that varies by gender. Among a group of tobacco-dependent subjects, individuals having one defective and one active copy of the gene CYP2A6 smoked significantly fewer cigarettes per day and per week than did smokers without an impaired copy of the CYP2A6 gene. Although it appears that individuals with this defective gene have reduced nicotine metabolism and are therefore protected, the manner in which this protection is imparted has not yet been clarified.  In a second study, data from large national samples of Scandinavian, Australian, and U.S. adult twins have demonstrated that genetic factors play an important role in predicting who among cigarette smokers will progress to being long-term persistent smokers. The association was much stronger for males than for females, however. 
The two studies above that point to a stronger genetic factor in cigarette smoking for males than for females are consistent with the behavioral literature indicating that nicotine dependence in females, compared with males, is controlled less by nicotine and more by other influences, such as the pleasurable social situations in which smoking occurs. Although women smoke fewer cigarettes per day, have a tendency to smoke cigarettes with lower nicotine content, and do not inhale as deeply as men, women have more difficulty achieving and maintaining abstinence than do men. Unfortunately, for females, nicotine replacement using nicotine gum or the nicotine patch is less effective than for males despite equal compliance with the regimen.
One of the most devastating consequences of drug use for females is the risk of HIV/AIDS. AIDS is now the fourth leading cause of death among women ages 15 to 44 years, and approximately two-thirds of the AIDS cases among women are related to injection drug use. One study has examined the influences of various psychological and social risk factors on needle-sharing among female intravenous drug users. The investigators found that although there were similarities between males and females, the role of the family, particularly the significant other, was more important in its effect on needle-sharing behavior in women than in men. The data from this study suggest that women's resilience and resistance to self-destructive behavior are closely related to ties with others. There was a main effect as well as mediating effects of protective family factors in women, buffering the risk factors leading to needle-sharing. 
Considerable research efforts are being devoted to HIV prevention among drug users. A recent study demonstrated that the effectiveness of HIV preventive interventions differs by gender. Sexual risks of HIV infection were more likely to decrease for drug-dependent men if the risk-reduction information was provided on the street, whereas counseling in an office setting was more conducive to risk reduction for drug-dependent women.
An aspect of drug use by women that is of particular concern is the use of drugs during pregnancy. Research indicates that pregnant drug users are at increased risk for miscarriage, ectopic (tubal) pregnancy, stillbirth, low weight gain, anemia, thrombocytopenia, hypertension, and other medical problems. In addition, their newborns may have lower birth weight and smaller head size than babies born to non-drug-using mothers. Of particular concern is that HIV can cross the placental barrier; in fact, among the total cases of pediatric AIDS in the United States, 54 percent are related to either maternal injection drug use or maternal sex with an injecting drug user. New data from a study of pregnant drug users suggest that a mother can also transmit hepatitis C virus to her unborn child and that this also increases the risk of maternal transmission of HIV to the fetus. In this study, drug use during pregnancy was highly correlated with hepatitis C infection, and the data suggest that maternal hepatitis C infection either enhances HIV transmission directly or is a marker for another cofactor, such as maternal drug use. Further study is needed to confirm the findings of this study and to determine whether the association represents a biologic effect of hepatitis C infection or results from a confounding interaction with drug use or other factors. 
Several studies are ongoing to determine the effects of maternal cocaine use on a child's development. One study has now gathered data on a poorly categorized group of women, namely, those from a rural population with little access to drug treatment. These data show that rural cocaine users were found more likely than their urban counterparts to be older, use other drugs, begin their drug use at an earlier age, have more depressive symptoms, have an external locus of control, have lower self-esteem, have a more simplistic understanding of child development, and have higher positive life event impact scores. However, both groups exhibited a very low level of reading skills, a finding that led to having to read the interviews and measures to each participant. This finding has important implications for health care and drug treatment programs. 
Initiation and Progression of Drug Abuse Among Women
Research is beginning to show that the progression or developmental stages of drug involvement are not identical for males and females. In the progression from legal drug use to illicit drug use, for example, cigarettes have a relatively larger role for females than for males, and alcohol has a relatively larger role for males than for females. With regard to initiation into illicit drugs, data suggest that women are more likely to begin or maintain cocaine use to develop more intimate relationships, whereas men are more likely to use the drugs with male friends and in relation to the drug trade. The onset of drug abuse occurs later for females, and the paths are more complex than for males. For females, there is typically a pattern of breakdown of individual, familial, and environmental protective factors and an increase in childhood fears, anxieties, phobias, and failed relationships; the etiology of female drug use often lies in predisposing psychiatric disorders prior to using drugs.
Childhood sexual abuse has been associated with drug use in females in several studies. Some studies indicate that up to 70 percent of women in drug use treatment report histories of physical and sexual abuse, with victimization beginning before 11 years of age and occurring repeatedly. A study of drug use among young women who became pregnant before reaching 18 years of age reported that 32 percent had a history of early forced sexual intercourse (rape or incest). These adolescents, compared with nonvictims, used more crack, cocaine, and other drugs (except marijuana); had lower self-esteem; and engaged in a higher number of delinquent activities.
Furthermore, female drug users may have greater vulnerability to victimization than males. For example, in a recent study of homicide in New York City, 59 percent of white women and 72 percent of African-American women had been using cocaine prior to death compared with 38 percent of white men and 44 percent of African-American men. Thus, although more males than females use cocaine, its use is a far greater risk factor for victimization for women than for men. Therefore, it is critical that the factors involved in the relationship between drug use and dependence among females and physical and sexual victimization (including partner violence) be identified and understood.
The rate of co-occurring substance use disorder and other psychiatric disorders is relatively high for females. Data from a study on female crime victims, for example, indicate that those suffering from posttraumatic stress disorder (PTSD) were 17 times more likely to have major drug use problems than nonvictims. In addition, individuals with a trauma history and PTSD use substance use inpatient services more frequently than do their non-PTSD counterparts. This fact has led researchers to speculate that the co-occurrence of substance use and PTSD may predict a more severe course than would ordinarily be present with either disorder alone. For females, a high correlation appears to exist between eating disorders and substance use. For example, as many as 55 percent of bulimic patients are reported to have drug and alcohol abuse problems. Conversely, as many as 40 percent of females with drug use or alcohol problems have been reported to have eating disorder syndromes, usually involving binge eating.
In one recent study, psychiatric and substance use comorbidity was assessed in opiate abusers seeking methadone maintenance. Rates of co-occurring mental disorders and personality traits were compared by gender, and the results showed that women were more likely than men to have a mood disorder and were seven times more likely than men to have a borderline personality disorder. Although all patients had at least one substance use diagnosis beyond opiate dependence, most often cocaine dependence, women were less likely than men to have a lifetime marijuana, alcohol, or hallucinogen disorder or current marijuana or alcohol dependence. 
Treatment Programs for Women
Women who abuse drugs face a variety of barriers, including barriers to treatment entry, treatment engagement, and long-term recovery. Barriers to entry include a lack of economic resources, referral networks, women-oriented services, and conflicting child-related responsibilities. Because women have many specific needs, a number of components of treatment have been found to be important in attracting and retaining women in treatment. These components include the availability of female-sensitive services; nonpunitive and noncoercive treatment that incorporates supportive behavioral change approaches; and treatment for a wide range of medical problems, mental disorders, and psychosocial problems.
One research study showed that treatment of drug-dependent women was more likely to be successful if treatment was provided in a mutually supportive therapeutic environment and addressed the following issues: psychopathology, such as depression; a woman's role as mother; interpersonal relationships; and the need for parenting education. Another study found that cocaine-using women whose children were living with them during residential treatment remained in the programs significantly longer than women whose children were not living with them at the facility. In this study, approximately 77 percent of the women with their children living in the treatment facility were still in the program at 3 months, compared with 45 percent of the group that did not have their children with them. At 6 months, the corresponding figures were 65 percent compared with 18 percent. The clear implication of this study is that providing facilities to accommodate children is a major factor in improving retention and outcome for drug-using mothers in treatment. In addition, having the children in the facility provides opportunities to assess and meet their needs, which may, in turn, affect the mother's prognosis. 
A recent national study of individuals in drug use treatment programs between 1991 and 1993 (DATOS) showed that women who had at least 28 days of treatment, with at least 14 days in short-term inpatient care, had sharp reductions in their use of illicit drugs, HIV risk behavior, and illegal activities. For instance, 84 percent of the women who were admitted to long-term residential treatment programs admitted at intake using illegal drugs every day or at least once a week. Twelve months after treatment, only 28 percent continued to abuse drugs. Women in short-term inpatient treatment also showed significant reductions in illegal drug use 1 year after their treatment, with 86 percent admitting use at intake and 32 percent reporting use after 1 year.
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