National Institute on Drug Abuse Biennial Report to Congress for Years 1999-2000

In the past several years, the National Institute on Drug Abuse (NIDA) has been actively promoting a research agenda on women, gender differences, and drug abuse. Whereas as recently as a decade ago, NIDA funded virtually no research on gender differences, today NIDA supports research in this area in all of its major program areas. From basic and field research on etiology and consequences of drug abuse to research on prevention and treatment, NIDA-supported research is repeatedly showing that gender matters in drug abuse. Leadership for NIDA efforts to promoted research on women and gender differences is provided by NIDAÕs Women and Gender Research Coordinator, Deputy Women and Gender Research Coordinator along with the Women and Gender Research Group which has representation from all of NIDAÕs program branches and Offices. The research findings summarized below, published in 1999 or 2000, are representative of NIDAÕs research on women and gender differences. These research findings fall into five major research areas: Biological Mechanisms and Consequences, Genetics, HIV/AIDS, Children and Adolescents, and Intervention Research: Prevention and Treatment.

BIOLOGICAL MECHANISMS AND CONSEQUENCES

Past NIDA research has indicated that the biological impact and the biological underpinnings of drug abuse are not always identical for males and females. Current research has expanded this knowledge base through its exploration of gender differences in the pharmacodynamics and pharmacokinetics of abused drugs, including the impact of hormonal systems. Animal research has addressed gender differences in self-administration, drug tolerance and withdrawal, as well as maternal functioning. And finally, research on the interactions between neuronal substrates of drug abuse and reproductive hormones hold promise for development of medications for drug dependence.

Cocaine Pharmacokinetics in Male and Female Rhesus Monkeys and Humans. Both animal and human studies have shown greater cocaine toxicity in males than in females. There has been little research focus, however, on the study of sex differences in pharmacokinetics and the relation it may have to cocaine's greater toxicity in males. A study of the pharmacokinetics of plasma cocaine in male and female rhesus following the intravenous administration of 0.8 mg/kg cocaine, conducted by researchers at Harvard Medical School, revealed that although females had significantly lower plasma cocaine levels than males ten minutes after injection, males and females did not differ in peak levels of cocaine, time to reach peak levels of cocaine in plasma, the elimination half life, or the area under the curve (Mendelson, Mello, & Negus, 1999). In a similar study by these researchers in which human subjects received intravenous cocaine, no sex differences were found in peak plasma cocaine levels, elimination half-life, or area of the curve, nor were sex differences observed in cardiovascular effects on heart rate and blood pressure or in the subjective report of feeling "high." In females, both the pharmacokinetic and pharmacodynamic measures were similar in the follicular and mid-luteal phases of the cycle. The single significant difference observed in the pharmacokinetic parameters was that the time to reach peak plasma levels was significantly lower in the follicular phase women (4 minutes) than in the luteal phase women (6.7 minutes) or in males (8 minutes). This work suggests that pharmacokinetic factors alone do not account for sex differences observed in cocaine toxicity (Mendelson, Mello, Sholar, Siegel, Kaufman, Levin, Renshaw, & Cohen, 1999).

Drug Self-Administration: Sex Differences and the Estrus Cycle in Rats. Researchers at the University of Minnesota have found that female rats acquire self-administration of intravenous cocaine and heroin self-administration significantly faster than male rats. Females acquired cocaine self-administration in approximately half the sessions required for males, and acquired heroin in about two-thirds the number of sessions required for males. For cocaine, but not heroin, significantly more females than males met the cocaine self-administration acquisition criterion. Following the acquisition of drug self-administration, the level of self-administered cocaine, but not heroin, was significantly higher in females than in males (Lynch, & Carroll,1999). In a follow up study, the researchers found that using a choice procedure, the average infusion dose of cocaine varied with the estrus cycle. It was highest during estrus and proestrus and lowest during metestrus/diestrus. Cocaine self-administration regulation, measured by the correlation between the mean interdose interval and the size of preceding dose, was significantly more precise in males and in metestrus/diestrus females as compared to estrus and in proestrus females. There was no difference in regulation between males and metestrus/diestrus females (Lynch, Arizzi, & Carroll, 2000).

Estrus Cycle Affects Cocaine Metabolism and Behavioral Response in Rats. In related work, Rockefeller University researchers have also shown that the estrus cycle plays a role in cocaineÕs effects. They found that when rats were administered cocaine in a ÒbingeÓ pattern, plasma levels of the cocaine metabolite, benzoylecgonine, increased more during metestrus-diestrus than during estrus and proestrus. Stereotypic behavior and locomotion were also greater during the same period (Quiniones-Jenab, Ho, Schlussman, Franck, & Kreek, 1999).

Contingent Versus Non-Contingent Cocaine: The HPA Axis and Sex Differences. Researchers at the University of Michigan Medical School and at Washington University have shown in rhesus monkeys that cocaine-produced increases in cortisol and ACTH release are greater and more dose-dependent when the cocaine (0.01-, 0.03-, 0.1-, and 0.3-mg/kg/injection) is delivered response-contingently (i.e., the subjects press a lever that produces an intravenous injection) than when it is delivered non-contingently (i.e., the intravenous injection is experimenter produced). Under both procedures, the cortisol response was higher in males than in females; there were no sex differences in the ACTH response. A single large dose infusion of cocaine (1 mg/kg) produced a substantially larger ACTH response in males than in females; there were no sex differences in the cortisol response to the large dose (Broadbear, Winger, Cicero, & Woods, 1999).

Sex Differences in Nicotine Self-Administration in Rats. Evidence has accumulated that there are sex differences in nicotine use and dependency in humans, although until recently, there was little corroborating evidence in animals. Researchers at the University of Pittsburgh have found that at the lowest dose of nicotine tested, female rats acquired nicotine self-administration faster than males, and they took more nicotine infusions. Female rats also displayed a shorter latency before self-administering the first nicotine infusion in a session. Self-administration in female rats did not vary with the estrus cycle, nor were there sex differences in either up-regulation of nicotinic receptor binding sites or in brain or plasma nicotine levels (Donny, Caggiula, Rowell, Gharib, Maldovan, Booth, Mielke, Hoffman, & McCallum, 2000).

Sex Differences in Morphine Preference in Rats. Researchers at Washington University School of Medicine have found that morphine serves as a positive reinforcer in a Òplace-conditioningÓ procedure in both male and female rats; however, the dose response curves markedly differ by sex. In the place-conditioning procedure, rats were placed in one chamber after morphine injection and placed in a different chamber following saline injection. Subsequently, the rats were given free choice between the two chambers for a period of 15 minutes. At doses ranging from 0.2 to 10 mg/kg, both males and females exhibited an increasing preference for the morphine-paired chamber. As the doses were increased to 17.5, malesÕ preference for the morphine-paired chamber dropped sharply, but for females, strong preference continued up to the highest dose tested, 30 mg/kg, which resulted in high lethality. Since no sex differences were observed in the blood and brain levels of morphine during the conditioning phase, the investigators speculate that these results may demonstrate intrinsic sex-linked differences in the sensitivity of the CNS to morphine's reinforcing properties (Cicero, Ennis, Ogden, & Meyer, 2000).

Female Rats Exhibit Less Morphine Antinociception, Tolerance, Withdrawal and Respiratory Depression Than Male Rats. Several rodent studies have shown that morphine's antinociceptive effect is weaker in females than males. Researchers at Washington State University have now reported sex differences in tolerance to morphine's antinociceptive effect. In the first experiment, acute single doses of either 3.0, 5.6, or 10 mg/kg morphine produced significantly greater hotplate and tail withdrawal antinociception in males than females, but delivery of all three doses spaced one week apart ("repeated dosing") did not produce sex differences. In males, morphine's antinociceptive effect was greater under acute dosing than under repeated dosing, whereas in females the effect was the same under the two procedures thus indicating greater tolerance in males. When morphine was delivered chronically twice daily, males exhibited significantly greater tolerance to morphine's antinociceptive effect than females and they exhibited greater recovery. Further, 7 of 31 males, but none of the 29 females, died of respiratory depression. In females, morphine produced a decrease in the number of proestrus and estrus days and an increase in diestrus days. When morphine withdrawal was precipitated by naloxone, withdrawal scores were significantly greater for males than females with the greatest sex difference occurring in number of "wet-dog shakes" (Craft, Stratmann, Bartok, & King, 1999).

Postpartum Separation from Offspring Produces Long-Lasting Anxiety-Like Reactions and Altered Morphine Sensitivity in Mother Rats. Prior research has shown that neonatal rat pups exposed to periodic separation from their mothers show an elevated stress-reactivity in adulthood that is manifest in both behavioral and physiologic indices. Researchers at Emory University School of Medicine now show that this separation also produces long-lasting changes in the dams. Dams separated from their neonatal pups for 3 hours daily on postpartum days 2-14 and tested four to six weeks post-weaning, exhibited anxiety-like behaviors measured via (a) both entries and time spent in the open arms of an elevated plus-maze, (b) time spent in the center of a novel locomotor arena, and (c) ultrasonic vocalizations. The separation also reduced sensitivity to morphine as measured by tail-flick and hot-plate tests of analgesia (Kalinichev, Easterling, & Holtzman, 2000).

Luteinizing Hormone-Releasing Hormone Affects Plasma Cocaine Levels Differently in Male and Female Monkeys. Considerable evidence points to the role of the brain neurotransmitter dopamine in the reinforcing effects of cocaine. Cocaine binds to the dopamine transporter, thus blocking the reuptake of dopamine and resulting in increased levels of dopamine at the synapse. Noting structural similarities between the dopamine transporter and luteinizing hormone (LH), a gonadatropin hormone released by the anterior pituitary, researchers at Harvard Medical School hypothesized that LH may bind to cocaine and thereby decrease cocaine levels. They report that when they administered synthetic LH-releasing hormone (LHRH) to male and female rhesus monkeys prior to the administration of cocaine, LH secretion significantly increased and peak plasma levels of cocaine significantly decreased in both males and females. In males, but not females, there was an inverse relationship between levels of LHRH-stimulated LH immediately prior to cocaine injection and peak plasma cocaine levels two minutes following cocaine injection. There were also gender differences in the levels of LH required to decrease plasma cocaine levels (70ng/ml in males versus 45 ng/ml in females). This research raises the possibility of developing LH or an LH-like molecule that will bind to cocaine as medication for use in the treatment of cocaine addiction (Mendelson, Mello, & Negus, 1999).

GENETICS

NIDA has devoted considerable research effort to understanding genetic factors associated with drug abuse. Studies in the past have indicated that vulnerability to drug abuse is linked to genetic factors and may not be the same for males and females. Current research provides additional evidence for this finding with findings related to cocaine-induced seizures, heritability of tobacco consumption, and initiation and subsequent misuse of drugs of abuse.

Candidates for the Genetic Basis for Individual Differences in Sensitivity to Cocaine Induced Seizures. Quantitative trait loci (QTL) studies are used to determine the number and chromosomal location of genes involved in complex behaviors that are influenced by more than one gene. Seizures are a well-known but poorly understood consequence of human cocaine abuse, particularly with respect to individual differences in susceptibility. In rodent models, sensitivity to cocaine seizures is strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. These findings prompted researchers at Oregon Health Sciences University to undertake a QTL study of cocaine-induced seizures in two populations derived from the C59BL/6 and DBA/2 mouse strains. Three QTLs emerged as significant one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive, both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males. The results suggest that different types of seizures have both common and distinct underlying mechanisms, and that there are a variety of factors that may account for individual differences in seizure sensitivity. Some of the QTLs were located in regions of the chromosomes that have been identified as QTLs for other seizure types such as a mouse model of epilepsy. Some of these chromosomal regions are also known to contain nervous system-relevant genes such as those for the dopamine D2 receptor, the serotonin 1B receptor, various glutamate receptors, and ion channel genes. These candidate genes can now be used as the basis of studies on the physiology of cocaine-induced seizures (Hain, Crabbe, Bergeson, & Belknap, 2000).

Heritability of Tobacco Consumption Varies by Gender and Time Cohort. A generation-spanning study of twins has provided the largest and most comprehensive analysis to date of twin data yielding heritability estimates for tobacco use. Researchers from the Medical College of Virginia and the Karolinska Institute in Stockholm, Sweden analyzed data from a Swedish registry of twins born since 1886. Comparison of monozygotic and dizygotic twin pairs yielded a heritability of 61% for males. The outcome for females was not the same and subsequent analyses were needed to understand the differences. What seemed to matter for females was the era of their birth: those born before 1925 had much lower heritability than those born since 1940. In fact, those females born since 1940 had essentially the same heritability (63%) as males. The researchers suggested that relaxation of the social restrictions on smoking in women after 1940 permitted greater manifestation of genetic factors influencing the risk for regular tobacco use (Kendler, Thornton, & Pedersen, 2000).

Factors in Drug Use Initiation versus. Misuse in Women. Researchers at the Medical College of Virginia applied a novel modeling technique to data from a sample of female twins, to estimate the role of genetic and environmental risk factors influencing initiation and subsequent misuse of illicit substances. A key feature of this approach is the capacity to distinguish between factors influencing initiation and misuse. The results suggest that shared environmental factors have a significant impact on the probability of drug use initiation, but no new influence on the risk for misuse once drug use is initiated. Furthermore, it appears that one set of genetic risk factors influences risk for initiation while another set appears important to the liability for misuse, once drug initiation has occurred (Kendler, Karkowski, Corey, Prescott, & Neale, 1999).

HIV/AIDS

For women, injection drug use (IDU), whether her own or that of her sexual partner, is the major risk factor for HIV/AIDS in women. Therefore considerable research effort by NIDA has been devoted to the study of women, gender, drug abuse, and HIV/AIDS. NIDAÕs women and gender research program on HIV/AIDS investigates etiology, pathogenesis, prevention and treatment. The studies summarized below highlight findings related to high-risk behaviors and coping skills, disease progression and manifestation, partner violence, and prevention and treatment related issues.

HIV Disease Progression in Female and Male Drug Users. Disease progression and mortality were prospectively assessed in a cohort of HIV-infected drug users (222 women and 302 men) attending a methadone maintenance program in New York City with on-site primary care. The researchers from Montefiore Medical Center and Albert Einstein Medical College in NY found that there were no statistically significant difference between males and females in the rates of CD4 cell decline, time to first CD4 count below 200 and clinical AIDS diagnosis, incidence and distribution of initial AIDS-defining illnesses, and mortality rates. These data indicate similar HIV disease progression in female and male drug users in methadone treatment with access to primary care. Interestingly, use of crack cocaine was an independent predictor of progression to AIDS, and women were more likely than men to report heavy cocaine use (Webber, Schoenbaum, Gourevitch, Buono, & Klein, 1999).

Comparison of Clinical Manifestations of HIV Infections Among Women by Risk Group, CD4 Cell Count, and HIV-1 Plasma Viral Load. Researchers at Johns Hopkins University compared the prevalence of HIV-related symptoms, physical examination findings and hematologic variables among 724 women whose risk for HIV was either injection drug use since 1985 or sexual contact. The women were participants in the HIV Epidemiology Research Study (HERS), a multi-center prospective study of HIV infection in women. Women who were injection drug users were more likely to report recent memory loss, and weight loss, and were more likely to have enlarged livers, a body mass index less than 24, and low hematocrit (<34%) and platelet count less than 150,000/ml than women who were not injection drug users. These outcomes in injection drug users may be due to effects of injections drug use rather than HIV infection since the difference in signs and symptoms found associated with increasing levels of viral load was not different across risk groups (Rompalo, Astemborski, Schoenbaum, Schuman, Carpenter, Holmberg, Warren, Farzadegan, Vlahov, & Smith, 1999).

Delays in Seeking HIV Care Due To Competing Caregiver Responsibilities. As part of the multi-site HIV Cost and Services Study, a study was conducted to investigate characteristics of HIV-infected individuals who delayed medical care for themselves because they were caring for others. The data, based on 2,864 adults, indicate that the odds were 1.6 times greater for women than for men to put off care. Persons without insurance and with CD4 cell counts above 500 were also significantly more likely to put off care. Those with a child in the household, primarily women, were 1.8 times more likely to put off care. These findings point to the need for women or those with a child in the household to be offered services to allow them to avoid delays in seeking their own medical care (Stein, Crystal, Cunningham, Ananthanarayanan, Andersen,Turner, Zierler, Morton, Katz, Bozzette, Shapiro, & Schuster, 2000).

Methadone Treatment and Antiretoviral Use among Injection Drug Users with AIDS. Use of antiretrovirals by 2,416 New Jersey injection drug users (IDUs) who had AIDS and were in methadone maintenance treatment (MMT) was analyzed using AIDS surveillance and Medicaid health care claims data. The Rutgers University researchers found that consistent participation in MMT was associated with a higher probability of antiretroviral use and, among antiretroviral recipients, more consistent use of antiretrovirals. Consistent MMT was more likely among women, whites, and older subjects. This research suggests that for AIDS-infected IDUs, consistent MMT may make receipt of appropriate HIV-related health care more likely and reinforce adherence to medical recommendations. Monthly total expenditures and inpatient expenditures were significantly lower for IDUs in MMT than for IDUs with claims indicative of current drug abuse (Sambamoorthi, Warner, Crystal, & Walkup, 2000).

Quality of Life Measures in the Miami HIV-1 Infected Drug Abusers (MIDAS) Cohort: Relationship to Gender and Disease Status. Researchers at the University of Miami report that among HIV-infected drug abusers, women have less social support than men. Using the Physician-administered Spitzer Index the investigators assessed activity, daily living, health, support and outlook in 75 HIV-infected drug abusers enrolled in the Miami HIV Infected Drug Abusers Study. Total composite scores were significantly lower in HIV-infected women than men. 45% of women were homeless or marginally housed as compared to 11% of the men. Women with low activity scores had less social support than women with high activity scores. Cocaine use was significantly related to reports of normal activity; more men used cocaine than women. Compared to non-AIDS participants, AIDS patients were more likely to have lower scores in health and poor outlook. These findings reveal specific deficits in areas of psychosocial capacity, particularly in HIV-1 infected women who abuse drugs, that may need to be strengthened in order to enhance function and adherence to treatment, as well as well-being (Shor-Posner, Lecusay, Miguez-Burbano, Quesada, Rodriguez, Ruiz, OÕMellan, Campa, Rincon, Wilkie, Page, & Baum, 2000).

Gender Differences in Delivery of HIV Risk-Reduction Services in Drug Treatment Programs. Researchers at UCLA and Texas Christian University investigated the receipt of HIV risk-reduction services among 4,412 drug abuse treatment patients in NIDAÕs National Drug Abuse Treatment Outcome Study (DATOS). These services included needle-risk reduction, sex-risk reduction, health-care options for HIV/AIDS, and general information on HIV/AIDS. The researchers found that these services were received by a higher percentage of individuals in long-term residential programs compared to clients in short-term inpatient, methadone maintenance, and outpatient drug-free programs. They also found that more men than women received HIV services. And although individuals who engaged in sex work had a higher likelihood than others of receiving HIV-related services, individuals with high-risk or multiple sexual partners were no more likely than others to receive HIV services. These finding suggest that more comprehensive service delivery is needed in order to reduce the risk for HIV among clients in drug treatment (Grella, Etheridge, Joshi, & Anglin, 2000).

Very Recent and New Injectors in NYC Have Very High Risks of Acquiring HIV. Using surveys conducted of injection drug users (IDUs) recruited from a large detoxification treatment program (n=2489) and a street store-front research site (n=2630) in New York City from 1990 through 1996, researchers at Beth Israel Medical Center in NY examined HIV infection and HIV risk behavior among new initiates into illicit drug injection. The interviews covered demographics, drug use history, and HIV risk behavior; serum samples were also collected for HIV testing. Subjects were categorized into two groups of newer injectors: very recent initiates (just began injecting to 3 years of injecting) and recent initiates (injecting 4 to 6 years); and long-term injectors (injecting 7 years or more). Of the 5119 study subjects, 954 (19%) were newer injectors, all of whom had begun injecting after knowledge about AIDS had become widespread among IDUs in the City. New injectors were more likely than long-term injectors to be female and white, and were more likely to have begun injecting at an older age. Median age at first injection was 27 years for very recent initiates, 25 years for recent initiates, and 17 years for long-term. Newer injectors generally matched long-term injectors in frequencies of HIV risk behavior. HIV infection was substantial among the newer injectors, and female new injectors had a higher seroprevalence rate than new male injectors. Among long-term injection users, however, no gender differences were found. Males who have sex with males had higher seroprevalence in all injection-duration groups. Overall, among new injectors, females, and men who had sex with men, African Americans, and Hispanics, were more likely to be infected (Des Jarlais, Friedman, Perlis, Chapman, Sotheran, Paone, Monterroso, & Neaigus, 1999).

Sexual and Drug Use Behaviors Among Female Crack Users: A Multi-Site Sample. Researchers at the University of Kentucky compared 2,658 female crack users who reported exchanging sex for drugs and/or money with 2009 female crack users who did not report exchanging sex for drugs and/or money. A 20-site sample of 4667 female crack users who participated in NIDAÕs AIDS Cooperative Agreement Project were interviewed. Although, both groups of women had frequent unprotected sex, women who exchanged sex had more sexual partners, had sex more often, used drugs before and during sex more often, and had a higher rate of STDs than women who did not exchange sex. In addition, African-American women, homeless women, and women who reported past substance abuse treatment were about twice as likely to exchange sex (Logan, & Leukefeld, 2000).

Partner Violence and HIV Risk among Women in Methadone Maintenance Programs. Analysis of in-depth interviews with 31 women in methadone maintenance treatment programs (MMTPs) in New York City who reported having experienced physical or sexual violence by an intimate partner during the past year revealed that 87% of the women reported experiencing a minor physical assault from an intimate partner within the past year, 58% reported experiencing a severe assault, 64.5% reported experiencing minor sexual coercion, and 12.9% reported severe sexual coercion. The researchers from Columbia University and Beth Israel Medical Center in NY also reported that 40% of the women indicated that both she and her partner were involved in drug-related activities during the most recent occurrence of partner abuse, 35% reported that only the partner was drug-involved, and only 6.4% of the women indicated that they alone were drug-involved. 20% reported using drugs immediately after the violent event because they were upset or in pain. Crack/cocaine was the drug most frequently mentioned by women reporting drug use before, during, or after the most recent violent event. For male partners, alcohol and crack/cocaine use were the most prevalent substances reported in conjunction with the most recent violent event. HIV risk behavior was high among these women with 20% reporting having unwanted sex after the most recent incident. Few women reported using condoms with their main partners; yet, two-thirds reported that they had outside relationships or suspected their partners of having outside relationships. 20% reported having exchanged sex for money/drugs within the past 90 days. 20% reported injection drug use within the past year. The multiple ways in which drugs of abuse are related to partner violence and HIV risk behaviors suggest the need for specific interventions for preventing drug relapse, and HIV and HCV infection among abused women in MMTPs (Gilbert, El-Bassel, Rajah, Foleno, Fontdevila, Frye, & Richman, 2000).

Cocaine Use and High Risk Sexual Behavior Among STD Clinic Patients. Researchers at UCLA and the University of Southern California examined factors associated with high-risk sexual behavior among 1,490 consecutive STD clinic patients (892 males and 598 females) attending three Los Angeles County STD clinics between 1992 and 1994. Among women, high-risk sexual behavior was associated with crack cocaine use and a perceived need for help. Among the men in the study, high-risk sexual behavior was associated with ethnicity (being black) and having an arrest history. These gender differences suggest that programs might employ different outreach and intervention strategies for women and men (Hser, Chou, Hoffman, & Anglin, 1999).

HIV Risk Behavior Greater Among Bisexual than Heterosexual Drug Users. Data from NIDAÕs multi-site AIDS Cooperative Agreement study was used to compare sexual and drug use behaviors of bisexual and heterosexual drug users, 435 males and 5,636 females. The University of Kentucky researchers found that for males, bisexuality was highly associated with using crack, sharing injection equipment and having an IV drug-using sexual partner in the month preceding the interview, being homeless, having ever been paid for sex, and having five or more sex partners in the month preceding the interview. For females, bisexuality was associated with ever using cocaine, and sharing injection equipment in the month preceding the interview, past substance abuse treatment, ever having been paid for sex, having five or more sexual partners in the month preceding the interview, and ever having been arrested. Overall, results from this study indicate that both male and female bisexuals, when compared to heterosexuals, were at higher risk for HIV and were more likely to be HIV positive. An implication of these results is that a universal prevention message may not be as effective as targeting prevention messages specifically for bisexual males and females (Logan, & Leukefeld, 2000).

Unprotected Sex Among Drug-Using Heterosexual Men and Women. Using the AIDS risk reduction model as a conceptual framework, researchers at the Rand Corporation and UCLA conducted a multivariate prospective test of psychosocial antecedents of unprotected sex using data from 155 female and 134 male heterosexual injection drug users in Los Angeles County. For both women and men, stronger intentions to use condoms predicted subsequent reduction in unprotected sex. For women, but not men, higher perceived self-efficacy also led to reductions in unprotected sex. These results suggest that explicit formation of risk-reduction intentions is an important antecedent to sexual behavior change by drug users of either gender and that change by drug-using women is also influenced by their perceived control over sexual risk-taking (Longshore, Stein, Anglin, & Kowalewski, 1998).

Gender Differences in Predictors of Drug Abuse and Sexual Risk Behaviors in an Impoverished Minority Population. Researchers at UCLA investigated predictors of drug abuse and sexual risk behaviors among 205 impoverished minority females (87% African-American, 13% Latina) and 203 males (89% African-American, 11% Latino) selected from individuals participating in a community-based educational AIDS prevention program in 9 homeless shelters and 11 residential drug recovery programs in Los Angeles. Gender differences were examined using among variables representing stress, self-esteem, avoidant and active coping strategies, and health outcomes of depression, escapist drug use, and sexual risk behaviors. Among both men and women, drug use and depression were positively related. There was strong relationship between stress and sexual risk behaviors among women, but not men. Women reported significantly more stress, depression, and avoidant coping styles than men. An avoidant coping style predicted escapist drug use among men whereas greater stress predicted escapist drug use among women. Greater stress, and lower self-esteem predicted depression in both men and women. Greater stress and less active coping predicted more sexual risk behaviors for women; however, no predictor construct was significantly associated with elevated sexual risk behavior among the men. These results suggest gender-specific leverage points for AIDS-risk reduction interventions (Stein, & Nyamathi, 1999).

CHILDREN AND ADOLESCENTS

The study of children and adolescents is included in many areas of NIDA-supported research, including epidemiology, etiology, consequences, prevention, treatment, and HIV/AIDS. Increasingly, this research focuses on gender differences and on females. The research described below highlights findings on prevalence, predictors, risk and protective factors, consequences and treatment. Minority populations are widely represented in the research subjects and include African Americans, American Indians, Asians, Hispanics and white non-Hispanics.

Gender Differences in Drug Use Traced to Differences in Opportunity to Use. Data from the 1993 National Household Survey on Drug Abuse was used by researchers at Johns Hopkins University to examine whether male-female differences in rates of drug use could be traced back to differences in rates of exposure to initial opportunities to try drugs, rather than to sex differences in the probability of making a transition to use following the initial opportunity to use. For marijuana, cocaine, hallucinogens, and heroin, the investigators estimated the proportions of males and females with an opportunity to use each drug and the proportions reporting use among those having an opportunity to use each drug. They found that while males were more likely than females to have an initial opportunity to use drugs, once an opportunity had occurred, males and females were equally likely to make a transition to initial use. These results suggest that the previously documented male excess in rates of drug use may be due to greater male exposure to opportunities to try drugs rather than to greater chance of progressing from initial opportunity to actual use (Van Etten, & Anthony, 1999).

Ethnic and Gender Differences in Drug Use, Offers, and Resistance. In a Arizona State University study, drug use, drug offers and drug resistance was surveyed in 2,622 seventh graders in the Phoenix metropolitan area. Significant ethnic and gender differences were found in drug use and, importantly, in the drug offer and resistance process. Consistent with the Johns Hopkins work described above, the researchers found that boys received more drug offers than girls. The offers to boys were most likely to occur in public and to come from parents and other relatives, and the message accompanying the drug offer was most likely to appeal to the benefits of drug use (self-image or social standing). Drug offers to girls, on the other hand, tended to occur in private (e.g., friendÕs home) and were most likely to come from a female acquaintance, a sister, female cousin, and boyfriends. Unlike offers to boys, offers to girls did not appeal to benefits of drug use, but rather focused on minimizing negative consequences of drug use. Of the three ethnic groups studied, Mexican Americans received the most offers and used the most drugs. They tended to receive drug offers by peer family members and at parties. European Americans tended to receive drug offers from acquaintances and at friendsÕ homes and on the street. African Americans tended to receive offers from dating partners and parents and in a park. The researchers found that these young adolescents (ages 12 and 13) do not possess large or sophisticated repertoires of strategies to resist drug offers and that whereas previous studies report that offers to older adolescents come from more intimate relationships, most offers to these younger adolescents come from acquaintances. This research suggests that age-, gender-, and ethnic-specific approaches are needed in prevention curricula (Moon, Hecht, Jackson, & Spellers, 1999).

Methamphetamine Use by High School Students. Researchers at the Tri-ethnic Center for Prevention Research at Colorado State University analyzed data on methamphetamine use by 629,722 U.S. high school students (9th through 12th) from 1989 to 1996. From 1989 through 1992, methamphetamine lifetime prevalence rates were low and stable for both males and females, but for each year after 1992, use increased each year for both males and females. By 1996, 4.6% of boys and 4.0% of girls reported having tried methamphetamine, percentages approximately double those reported in 1992. Use rates in western states were approximately twice those in eastern states. American Indians and Hispanics were most likely to use methamphetamine, followed in order by Asian Americans, White non-Hispanics, and African Americans. Compared to other heavily drug involved youth, methamphetamine users were more likely to use other drugs. Almost all (90%) methamphetamine users used marijuana and 90% used a drug other than marijuana in the prior month (Oetting, Deffenbacher, Taylor, Luther, Beauvais, & Edwards, 2000).

Flunitrazepam Becoming Health Concern to Sexually Active Young Women in Southwestern U.S. Flunitrazepam ("Rohypnol," a date-rape drug) is a short-acting benzodiazepine with general properties similar to those of diazepam. Researchers at the University of Texas Medical Branch at Galveston conducted a cross-sectional survey to determine prevalence, patterns, correlates and physical effects of voluntary flunitrazepam use in a sample of 904 sexually active adolescent and young women 14 to 26 years of age using university-based ambulatory reproductive health clinics. Lifetime use was reported by 53 or 5.9% of subjects, with frequency of use ranging from 1 to 40 times. Flunitrazepam was taken most often with alcohol (74%), and 49% took it with other illicit drugs. Users were significantly more likely than were nonusers to report lifetime use of marijuana or LSD, to report having a peer or partner who used flunitrazepam, to report pressure to use flunitrazepam when out with friends, and have a mother who had at least a high school education. Finally, 10% of voluntary users reported experiencing subsequent physical or sexual victimization. Voluntary use of flunitrazepam is becoming a health concern to sexually active young women who reside in the southwestern United States. Young women who have used LSD or marijuana in the past or who have a peer or partner who used this drug appear to be at the greatest risk (Rickert, Wiemann, & Berenson, 1999).

Females At-Risk for Anabolic Steroid Use. Three national surveys document an increasing prevalence of young women's anabolic steroid (AS) use. Both local survey and national data indicate prevalences of AS use among young women of approximately 1%. Predictors of AS use and the relationship to disordered eating behavior (DEB) have not been defined. Researchers at The Oregon Health Sciences University surveyed 2,090 middle and high school-aged females using a 140-item questionnaire. Tendency toward DEB and physique-altering drug use (including AS) and potential risk factors in the domains of knowledge, beliefs, psychological factors, peer/ environmental effects, demographics, drug use, and deviant behaviors were assessed. One-hundred and eleven (5.3%) subjects indicated a high intent for future AS use. Of those at high risk for DEB (24% total), 12% also were at risk for AS use. Those at risk for both DEB and AS use also indicated greater use of supplements, cocaine, alcohol and diet pills. They also exhibited less belief in AS adverse effects, greater perceived peer AS use, and more sexual partners. Those at risk for DEB were also at risk and exhibited more deviant behavior. Because similar predictors are present for DEB and AS use, programs designed to prevent DEB also should address AS use (Elliot, Moe, Duncan, & Goldberg, 1999).

Gender Differences in Marijuana Use Among American Indian Adolescents. Researchers at the University of Colorado Health Sciences Center report two studies of marijuana use among American Indian adolescents. The first study examined the characteristics of marijuana (MJ) users in a survey of 1464 9th-12th-grade adolescents from four Indian tribal groups. Forty percent of these subjects had used MJ at least once in the last month. Low- and high-frequency marijuana use (1-3 times in the past month, and 11 or more times in that period, respectively) and their predictors varied by gender. Males were no more likely than females to use MJ at a low frequency, but were more likely to use at high frequency. Low-frequency MJ use among females was associated with reporting that peers encouraged alcohol use as well as use of both alcohol and stimulants. Among males, low-frequency use was associated with greater positive alcohol expectancies, lower grades in school, and alcohol use. While high-frequency MJ use was associated with use of alcohol, stimulants and cocaine among females, high frequency among males was associated with higher scores on the antisocial behavior scale as well as the use of alcohol, stimulants and cocaine (Novins, & Mitchell, 1998). The second study examined the developmental course of marijuana use among 1766 American Indian adolescents, 14-20 years old, across three cultural groups. Three annual ascertainments of 30-day marijuana use and 5 age cohorts were studied. Use of marijuana increased in middle adolescence, peaked in later adolescence, and began to decrease in early adulthood. Both gender and community differences were observed in the trajectories, with girls and boys exhibiting similar frequency of use at age 14 but diverging by age 20; in all three communities, males showed a sharper increase in use (Mitchell, Novins, & Holmes, 1999).

Gender Differences in Validity of Drug Use Reporting by Juvenile Arrestees. In an exploratory study, investigators at the University of Illinois at Chicago examined gender differences in the validity of drug use reporting among 6,377 juvenile arrestees in a sample drawn from the Drug Use Forecasting Program for 1992-1996. Self-reported marijuana and crack and/or cocaine use was compared to urinalysis results to test gender differences in the accuracy of disclosure. The researchers found that girls were more likely then boys to disclose marijuana use, but were as likely as boys to disclose cocaine use, except among Hispanics where Hispanic girls were significantly more likely than Hispanic boys to under report recent cocaine use. Among arrestees from homes with one or no parents, girls were significantly more likely than boys to disclose recent cocaine use (Kim, Fendrich, & Wislar, 2000).

Adolescent Substance Abuse: Gender, Timing, and Psychiatric Comorbidity. Researchers at Duke University used data from 1,420 children in a population-based longitudinal study, based on children in 11 counties in western North Carolina, to examine gender, timing, and psychiatric factors in drug abuse. They found that girls who developed use or dependence initiated drug use later than girls who did not develop use or dependence. Boys, on the other hand, who developed use or dependence used earlier than boys who did not develop use or dependence. Depression was a stronger predictor of drug use in boys than in girls, and conduct disorder was a stronger predictor of drug use and dependence in girls than in boys. This study is notable for the size of the sample and the sophistication of the methodology and analyses, enabling new observations about development and gender in regard to onset of substance use problems (Costello, Erkanli, Federman, & Angold, 1999).

Peer Difficulties and Parental Stress Differentially Affect Monthly ÒBurstsÓ in Adolescent Drug Use. Researchers at the Oregon Social Center and the University of Oregon examined whether monthly bursts in substance use (tobacco, marijuana, alcohol) were related to variations in family and peer relations. Using a structured protocol, monthly telephone interviews were conducted with 181 young adolescents, ages 11-14 yrs old, and their parents. The results were analyzed separately for one- and two-parent families, for both boys and girls. In each family type, exposure to deviant peers (i.e., peers of whom parents disapproved or who smoked, drank, or used drugs) was a predictor of substance use in the same month for both boys and girls. For girls in single-parent families, but not in two-parent families, parental stress was a predictor. Parental stress was not a predictor for boys in either family type. For boys in both family types, peer difficulties (e.g., being teased or ignored, arguments, fights, hurt feedings) was a predictor, but was not a predictor for girls in either family type. These findings highlight the utility analyzing data on predictors of drug use in adolescents by gender and they suggest that the effectiveness of intervention programs for high-risk may be enhanced by targeting gender-specific issues (Dishion, & Skaggs, 2000).

Home Alone and Cigarette Smoking in Urban Minority Youth. In a sample of 228 6th grade urban minority youth, Cornell University researchers found that unsupervised time alone at home had opposite effects on cigarette smoking in girls and boys. More unsupervised time alone was associated with less smoking for boys, but more smoking for girls. The effect for girls was particularly strong in girls from two-parent families. The researchers speculated that smoking may be more closely tied to social activities in boys than in girls and that girls may be more likely to smoke for non-social reasons such as weight control (Griffin, Botvin, Scheier, Diaz, & Miller, 2000).

Childhood Sexual Abuse Predicts Adult Psychiatric and Substance Use Disorders in Women. Researchers at the Medical College of Virginia used a genetically-informed design and population-based sample of 1411 female adult twins to explore the association between childhood sexual abuse and adult psychiatric disorders, including alcohol and substance abuse, assessed retrospectively. They found that women who reported childhood sexual abuse are at substantially increased risk to develop a range of psychopathologic outcomes, particularly alcohol and substance use disorders, primarily due to more severe sexual abuse. Of note, this relationship held when parental psychopathology was controlled in the analyses, suggesting that the relationship between childhood sexual abuse and adult outcomes is indeed causal. Although the association between sexual abuse and psychopathology has been reported previously, this study is remarkable for applying methodology that can help distinguish between association and causation by including family factors and using a co-twin report method in a population-based sample (Kendler, Bulik, Silberg, Hettema, Myers, & Prescott, 2000).

Childhood Sexual Abuse Among Female Addicts and Subsequent Parenting. The relationship between childhood sexual abuse (CSA), family of origin and the status of 248 female narcotic addicts currently raising adolescent children was examined by researchers at Friends Research Institute, Inc. in Baltimore. Seventy-eight of these women reported a history of CSA. The CSA group and the non- CSA group were compared on variables related to parental substance abuse, parenting behavior, and other family dynamics (retrospectively for families of origin and contemporaneously for current families). Findings suggest that the abuse of alcohol by the mothers of some of the CSA subjects was a contributing factor in creating an environment or set of circumstances in which the abuse took place. The two groups also differed on variables such as involvement, attachment, responsibility, discipline, and punitive actions. CSA was also related to addiction careers, parental substance use, adult psychological symptoms, and home atmosphere (Blatchley, Hanlon, Nurco, & OÕGrady, 2000).

Stressful Life Events and Adolescent Substance Use and Depression: Conditional and Gender Differentiated Effects. Stressful life circumstances have myriad influences on human health and behavior. Recent research indicates that age plays a role in these influences. Adolescent reactions to stressful life events, for example, are often inconsistent with adult reactions to similar life situations and transitions. Researchers at the University of Chicago assessed the gender distinct effects of stressful life events on two outcomes among adolescents, substance use and depressive symptoms during the prior 30 days. The data were from 601 families, predominately white, participating in a longitudinal study that began in 1991. Results indicated that in both boys and girls, stressful life events affect substance use when peer drug use is high. Further, stressful life events affects substance use in girls, but not boys, when parental support is low; and, they affect substance use in boys, but not in girls, when involvement in conventional activities is low. And, stressful life events affect female, but not male, depressive symptoms, especially when self-esteem is low (Hoffmann, & Su, 1998).

Girls' Smoking Influenced More By Parents but Boys' Smoking Influenced More by Peers. In a study of the effects of parental and peer approval of smoking on adolescent smokers' current levels of cigarette use, researchers analyzed data for 913 California 7th-grade students who had previously initiated cigarette use. Researchers at the Georgetown University in Washington, DC and the University of Illinois applied a Poisson random-effects regression model to examine the number of cigarettes smoked in the past month as a function of race/ethnicity, gender, number of friends approving smoking, and parental approval. A correlation was found between level of smoking and extent of peer and parental approval. However, a stronger relationship between parental approval of smoking and current level of smoking was found for female adolescents than for male adolescents. Conversely, a stronger relationship between peer approval of smoking and current level of smoking was found for male adolescents than for female adolescents. With respect to race, the influence of parental approval of smoking on adolescents' current level of smoking was generally more pronounced for minority adolescents, relative to white adolescents. The influence of peer approval of smoking on current level of smoking, however, was strongest for white adolescents and was less strong for black, Hispanic, and Asian adolescents. The findings suggest that smoking cessation programs among adolescents may need to target both parent and peer influences, but these influences may vary by gender and race/ethnicity (Siddiqui, Mott, Anderson, & Flay, 1999).

Relationship of ADHD, Depression and Non-Tobacco Substance Use Disorders to Nicotine Dependence in Substance-Dependent Delinquents. In a study of 367 male and female behaviorally disordered juvenile delinquents, 13 - 19 years old, researchers at the University of Colorado School of Medicine found that attention deficit hyperactivity disorder (ADHD) and major depression significantly contributed to the severity of nicotine dependence in adolescents diagnosed with a non-tobacco substance use disorder (SUD). ADHD was associated with earlier onset of regular smoking in males, and the severity of non-tobacco SUD was related to nicotine dependence severity in both boys and girls (Riggs, Mikulich, Whitmore, & Crowley, 1999).

Adolescent Drug Use and Adult Drug Problems in Women. Researchers at the University of Southern California and UCLA examined the relationship between adolescent drug use, and other variables assessed in adolescence, and later problems in adulthood in a community sample of 327 women who were participants in a 13-year longitudinal study. One focus of the longitudinal study was factors that might exacerbate or attenuate the effects of early drug consumption on later drug problems, including sensation seeking, social conformity, academic orientation, parental support, depression, and drug problems in parents. Results showed that the strongest predictor of adult polydrug problems was adolescent drug use, which overwhelmed both personality factors and parental factors. High sensation seeking and low social conformity were also strong factors in predicting adult drug problems. The effects of sensation seeking are consistent with the view that this variable reflects a sensitivity to drug use that makes it more likely that drug use gets translated into drug abuse (Stacy, & Newcomb 1999).

Brain Morphology Changes After Early and Chronic Marijuana Use. Marijuana is the most commonly illegal drug in the US, and where considerable research attention has focused on its acute effects, there is little research on whether its chronic use is associated with morphological changes in the brain. Duke University Medical Center researchers used positive emission tomography (PET) to assess cerebral blood flow (CBF) and magnetic resonance imaging (MRI) scans to evaluate brain volume in 57 individuals, age 19 to 48, with a history of teenage marijuana use. The age at first use ranged from age 11 to 21. Since a significant degree of brain development occurs during adolescence, the researchers compared findings between individuals who initiated marijuana use early (before age 17) with those who initiated use later (age 17 or later). The researchers found that male and female early-initiators had lower percent cortical gray matter and higher percent white matter volumes than their late-initiating counterparts, suggesting that the effect reflect effects on brain development rather than atrophy. The CBF of females was greater than for males and did not differ in the females who initiated early and late. In males, however, early initiators had higher CBF than late initiators. Both male and female early initiators were physically smaller in height and weight, with the effects being greater in males. None of the observed findings were related to the duration of use of marijuana. Given prior work demonstrating a normal developmental decrease in gray matter during adolescence, the present findings suggest that marijuana may accelerate that developmental process. Moreover, given that THC (the major psychoactive ingredient in marijuana), alters gonadal and pituitary hormones, those alterations may play a role in the changes in cortical gray area and CBF in late versus early initiators. The average age of first marijuana use in this study was 14 for both males and females. At that age, females have already experienced the pubertal increase in rate of growth hormone release which typically occurs at age 11 to 12, whereas males experience this increase typically at age 13 to 14. Since THC suppresses growth hormone release, its impact on 14-year-old youth, therefore, would be expected to be greater on males than on females. Overall, these findings suggest that exposure to marijuana (and possibly other drugs) at certain critical periods such as during early adolescence, may alter normal patterns of development and that these changes may be gender-based (Wilson, Mathew, Turkington, Hawk, Coleman, & Provenzale, 2000).

Sex Differences in Language Production in 24-Month-Old Inner City Children Exposed In Utero to Cocaine. Researchers at the Yale Child Study Center compared the language abilities at age 24 months of 47 inner-city children exposed prenatally to cocaine with those of 30 inner-city children not exposed prenatally to cocaine. The sample was recruited prenatally. While both groups of children evidenced some delays in language development, the non-cocaine-exposed children produced more complex language, including longer utterances, a richer vocabulary, and more complex grammatical structure than the cocaine-exposed children were able to do. The effect, however, was largely in girls (Malakoff, Mayes, Schottenfeld, & Howell, 2000).

Children, Particularly Sons, of Opiate Addicts with Major Depression at Increased Risk for Conduct Disorder and Global, Social, and Intellectual Impairment. Researchers at Columbia University evaluated 114 children of 69 white methadone maintenance patients with and without major depression. The children ranged in age from 6 to 17 years. Sons of opiate addicts with major depression were at increased risk for conduct disorder and global, social, and intellectual impairment compared with sons of opiate addicts without major depression and/or sons of controls with neither drug dependence nor depression. Sons of opiate addicts without major depression differed little from controls. Daughters of opiate addicts did not differ from controls in rates of disorders but had poorer social adjustment and nonverbal intelligence. Treatment settings such as methadone maintenance might afford an opportunity for primary and secondary prevention, both through early detection of childhood disorders and treatment of parental drug dependence and psychopathology (Nunes, Weissman, Goldstein, McAvay, Seracini, Verdeli, & Wickramaratne, 1998).

Maternal Smoking During Pregnancy: A Sex Differences in Offspring Psychopathology. Data from a Columbia University longitudinal have replicated findings from several other reports of an association between maternal smoking during pregnancy and conduct disorder and substance abuse in offspring. In the population sample of 147 offspring and mother pairs who were interviewed three times over a period of ten years, 97 of the women did not smoke during pregnancy and 50 smoked more than 10 cigarettes almost daily during pregnancy. The researchers found that among offspring of mothers who smoked during pregnancy, girls showed a 5-fold increased risk of adolescent drug dependence and boys showed a 4-fold increased risk of early onset conduct disorder. Controlling for several relevant factors such as maternal substance abuse during pregnancy and parental diagnosis did not alter the findings. These findings, based on prospective longitudinal data, underscore concerns about the potential impact of prenatal exposure to maternal smoking and highlight the need for such research to examine outcomes by gender (Weissman, Warner, Wickramaratne, & Kandel, 1999).

Gender Differences in Comorbidity and Family Dysfunction. Researchers at the University of Miami investigated gender differences in patterns of co-morbidity and family functioning among a sample of 95 substance-using youths, age 13-17 years, referred by juvenile justice, education and social welfare for substance abuse treatment. Findings indicate that the girls not only used drugs and engaged in externalizing behaviors (e.g., delinquency, aggression) as extensively as the boys, but they also had higher levels of internalizing symptoms (e.g., anxious, depressed, withdrawn, bodily complaints). Moreover, the families of girls exhibited more conflict and less family cohesion than families of boys. These finding point to the need for drug abuse treatment for adolescent girls that not only addresses their internalizing and externalizing disorders, but also focuses on improving family functioning (Dakof, 2000).

Substance Use, Mental Disorders, Abuse and Crime: Gender Comparisons Among a National Sample of Adolescent Drug Treatment Clients. Gender comparisons in drug and alcohol use, illegal activity, physical and sexual abuse, and mental health problems were made in a sample of 3,382 adolescents who were treated from 1993 to 1995 in adolescent-oriented drug programs that participated in the NIDAÕs multi-site Drug Abuse Treatment Outcome Study of Adolescents. Most of the adolescents reported regular use of marijuana and alcohol. Males had higher rates of illegal activity and involvement with the juvenile justice system. Females reported more sexual abuse, while males reported more physical abuse. Males and females had equal rates of conduct disorder and attention deficit hyperactivity disorder, although in the general population, these disorders are more prevalent in boys (Rounds-Bryant, Kristiansen, & Hubbard, 1999).

Prevention of Smoking Initiation and Escalation in Early Adolescent Minority Girls. Researchers at Cornell University examined the effectiveness of a drug abuse prevention program in reducing the initiation and escalation of smoking in a sample of predominantly minority 7th grade girls from 29 New York City public schools. The 15-session prevention intervention taught social resistance skills within an intervention designed to promote personal and social competence skills. Smoking rates among 1,278 girls who received the program were compared with those of a control group of 931 girls. Girls in the intervention group were less likely to initiate smoking compared to girls in the control group. There were also significant program effects on smoking intentions, smoking knowledge, perceived peer and adult smoking norms, drug refusal skills, and risk taking. Experimental smokers in the intervention group also were less likely to escalate to monthly smoking relative to controls (Botvin, Griffin, Diaz, Miller, & Williams, 1999).

INTERVENTION RESEARCH: PREVENTION AND TREATMENT

NIDA supported treatment research in 1999 and 2000 has shown considerable effort directed toward gender differences in all aspects of the treatment process. Research has provided data on individual differences in characteristics of patients at treatment entry, gender differences in needs and services, and gender differences in factors that affect treatment engagement, retention, and outcomes. Research has compared women-only and mixed-gender treatment programs, studied issues regarding postpartum and parenting women, and investigated the role of menstrual cycle. Findings also include data on predictors of substance abuse among the homeless and prevention interventions for rape victims.

How Are Women Who Enter Substance Abuse Treatment Different than Men?: A Gender Comparison from the Drug Abuse Treatment Outcome Study. Gender differences at treatment admission were examined in a large national sample of 10,010 men and women entering drug abuse treatment in NIDAÕs multi-site Drug Abuse Treatment Outcome Study (DATOS). The researchers at Research Triangle Institute in NC who conducted the analysis found that women were younger and less educated than men and had been employed less. Although some drug use patterns were similar, women reported greater daily use of cocaine while men reported more alcohol use. Women reported more problems related to health and mental health, as well as higher levels of past and current physical and sexual abuse. Both men and women who had custody of children showed concern that drug treatment might affect their custody, but most other issues related to children were primarily women's issues (Wechsberg, Craddock, & Hubbard, 1998).

Detoxification Centers: Who's in the Revolving Door? Data from 443,812 admissions to publicly funded detoxification centers in Massachusetts from 1984 to 1996 were analyzed by Brandeis University to assess changes in the population served. Substantial increases in admissions of women, African Americans, and Hispanics were apparent. Mean age at admission declined and unemployment increased. A 25% decline in admissions reporting alcohol use was coupled with a twofold increase in reported cocaine use and a fourfold increase in heroin use. These findings indicate that the older, white, male alcoholic is no longer the primary consumer of detoxification services. Policy initiatives (e.g., increased services for women) and the changing epidemiology of drugs abuse (e.g., increased access to heroin) have contributed to the changing population served in detoxification centers (McCarty, Caspi, Panas, Krakow, & Mulligan, 2000).

Gender Differences at Admission and Follow-Up in a Sample of Methadone Maintenance Clients. Although one-third of clients enrolled in methadone treatment (MMT) in the United States are female, few studies have examined gender differences at admission and at follow-up. An understanding of these differences can lead to improved treatment strategies for both men and women. In NIDAÕs muli-site Drug Abuse Treatment and AIDS-Risk Reduction (DATAR) project, interview data collected at admission from 435 opioid dependent clients (31% female) found females to have more dysfunctional families of origin and greater prior and current psychological and medical problems. The Texas Christian University researchers who conducted the study also found that follow-up data collected approximately one year after discharge indicated that both genders showed significant improvement from admission to follow-up in terms of reduced drug use, criminal activity and HIV/AIDS-risky behaviors. In some areas such as improved family relationships and improved psychosocial status, females seemed to benefit more from treatment than did the males. In addition, females were more likely to seek further help for both drug misuse and psychological problems subsequent to discharge (Chatham, Hiller, Rowan-Sal, Joe, & Simpson 1999).

Client Needs and Services Provided during Methadone Maintenance Therapy: A Gender Comparison. A sample of 635 clients admitted to three community-based methadone treatment programs participating in NIDAÕs multi-site Drug Abuse Treatment for AIDS-Risk Reduction project was used by researchers at Texas Christian University to examine gender differences in client needs and services provided during the first 3 months of treatment. Compared to males, women entering treatment were younger, more highly motivated, more likely to be unemployed and have more dependent children, entered treatment with more psychological symptoms, and reported more illegal tranquilizer use and more HIV/AIDS-risk behaviors. Compared to females, males more frequently reported alcohol problems and criminal/legal issues. In most cases services provided were consistent with needs; however, some gender differences in services needs were not differentially addressed. Although womenÕs needs were greater in the areas of employment and HIV/AIDS-risk behavior, counselors addressed these topics equally between the genders. Additionally, females received significantly more medical services than males, although there were no gender differences in health problems reported at admission. Counselors also reported that different counseling strategies were used depending upon gender. Strategies used with females were more often directed toward developing problem-solving and communication skills (Rowan-Szal, Chatham, Joe, & Simpson, 2000).

Characteristics of Women-Only and Mixed-Gender Drug Abuse Treatment Programs. Researchers from UCLA and the University of Houston used data from 294 drug abuse treatment programs in Los Angeles County to compare the characteristics of women-only (WO) and mixed-gender (MG) programs. A program was designated as either WO or MG based on current enrollment rather than program policy. The researchers found that WO programs were uniformly more likely than MG programs to provide services specific to womenÕs needs such as parenting classes, childrenÕs activities, and prenatal, postpartum and pediatric services. They were less likely than MG programs to charge a fee or to accept payment through third-party and more likely to receive payment through the Medicaid system. MG programs were more likely to provide group and family therapy than WO programs, whereas WO programs were more likely than MG programs to provide peer support groups. Services that directly address the need for practical and vocational skills were likely to be found in WO programs, as were programs that offered training in anger management, and programs of longer treatment duration. The differences in program characteristics reflect in part broader societal gender differences, including women's generally lower economic status and primary responsibility for child-rearing (Grella,Polinsky, Hser, & Perry, 1999).

Women in Women-Only and Mixed-Gender Residential Drug Treatment: Characteristics and Outcomes. Researchers at UCLA compared characteristics of 4,117 women treated in publicly funded residential drug treatment programs in Los Angeles County between 1987 and 1994 in order to determine predictors of program completion. Comparisons were made between women-only (WO) and mixed-gender (MG) programs and by pregnancy status. Women in WO programs were more likely than women in MG to be pregnant, homeless, or on probation; and they were more likely to use methamphetamine and alcohol and to have prior drug treatment. Pregnant women were younger, more likely to be homeless, had fewer years of drug use, were more often referred by other service providers, and were less likely to have injected drugs or have prior drug treatment than non-pregnant women. Of particular clinical significance, although women in WO programs had more problems, they spent more time in treatment and were more than twice as likely to complete treatment as compared with women in MG programs (Grella, 1999).

Gender Differences in the Predictors of Client Engagement in Drug Treatment. A study of why some clients are more likely to engage in treatment than others indicates that the predictors of treatment engagement are generally confined to current treatment experiences and they differ by gender. Researchers at UCLA found that among clients entering 25 Los Angeles metropolitan out-patient treatment facilities, for females, the most powerful predictors of treatment engagement were perceived helpfulness of medical services, followed by level of pretreatment alcohol use and perceived concern of the counselor. For males, predictors were perceived helpfulness of medical services, transportation services, relapse prevention training, and the perception that counselors were very helpful. Client characteristics were generally not strong predictors of treatment engagement. Data concerning the client-counselor relationship suggest that women may respond more favorably to an empathic counseling style, whereas men may respond to a more utilitarian style. The findings contradict popular stereotypes about the treatment-receptive client, identify possible directions for treatment improvement, and highlight the need for more research examining the treatment experience of the client (Fiorentine, Nakashima, & Anglin, 1999).

A Search for Strategies To Engage Women in Substance Abuse Treatment. In order to remain in treatment, patients must initially engage in the treatment process, and clinicians seek motivational strategies to draw each patient into the treatment process. In a study of 102 pregnant and/or parenting female outpatient clients who were offered child care, Thomas Jefferson University researchers found that while the need for child care was great among these women, this service was greatly under-utilized. Reasons cited by the women included fear of being reported to Child Welfare for having neglected their children, lack of familiarity with the child care providers, lack of experience in leaving their children with people not well known to them, and difficulty in having to groom children and transport them to the program for intake appointments. Addressing these concerns within the treatment context could serve to enhance utilization of child care services and thereby serve to enhance engagement in the treatment process (Comfort, Loverro & Kaltenbach, 2000).

Program Variation in Treatment Retention Outcome and Among Women in Residential Drug Treatment. A study of program characteristics associated with treatment retention among 637 women in 16 residential drug treatment programs was conducted as part of NIDAÕs Drug Abuse Treatment Outcome Study. UCLA researchers found that Women who were pregnant or had dependent children had higher rates of retention in programs in which there were higher percentages of other such women. Programs with higher proportions of pregnant and parenting women provided more services related to women's needs. Longer retention was associated with higher rates of post-treatment abstinence. The findings support provision of specialized services and programs for pregnant and parenting women (Grella, Joshi, & Hser, 2000).

Pregnant Cocaine-Dependent Women in Residential and Outpatient Substance Abuse Treatment: Treatment Retention and Birth Weight. In a sample of 64 pregnant cocaine-dependent women and their infants, researchers at Thomas Jefferson University compared treatment retention, biopsychosocial characteristics, and birth weight outcome for women who were enrolled in residential versus outpatient treatment. Both programs provided comprehensive services including high-risk obstetrical care, psychiatric services, addiction and therapeutic counseling, case management, HIV testing and counseling, and parent-child services. Analysis of the biopsychosocial characteristics revealed that women receiving residential treatment had greater housing problems and psychiatric illness than those receiving outpatient treatment. The birth weight outcomes in the two groups were not significantly different, even though women in the residential program were able to attain abstinence while total abstinence was not attainable for the outpatient clients. With respect to retention, one third of the clients departed from both the residential and outpatient programs during the first three months following admission; however, two months postpartum, the outpatient program lost twice as many clients than did the residential program (Comfort, Kaltenbach, 1999).

Gender Differences in Early Treatment Termination among of Opioid-Dependent Outpatients: Role of Hostility. In a University of Vermont study of 104 opioid-dependent patients in a buprenorphine-maintenance treatment program, 13% of the males and 25% of the females stayed in treatment less than 30 days. Analysis of predictors of early treatment termination indicated that the patients with less severe legal problems and greater employment problems were more likely to terminate. In females, but not in males, higher levels of hostility predicted early treatment termination. Opioid-dependent females also were found to have significantly higher scores on the Buss-Durkee Hostility Scale than males. These findings that hostility is a predictor of their premature termination of treatment and that female heroin addicts have higher levels of hostility than males suggest that hostility should be assessed early in treatment and that increased effort may be needed to enhance participation of hostile women in treatment programs (Petry, & Bickel, 2000).

Predictors of Substance Abuse Treatment Retention Among Women and Men in an HMO. Although research has examined treatment retention in public drug treatment programs, little is known about factors that influence treatment retention in an insured outpatient population. A team of researchers affiliated with Kaiser Permanente Medical Care Program in Oakland, CA, has identified some gender-based differences in retention rates in men and women in outpatient alcohol and drug treatment programs (abstinence based day hospital and traditional outpatient modalities). The researchers followed 317 women and 599 men who were admitted to the HMO program during a 2-yr period. They found that fewer and less severe drug problems were predictors of increased retention for both men and women; however, most predictors were gender-specific. Among women, higher retention was predicted by having an income of $20,000 or higher, belonging to ethnic categories other than African American, being unemployed, being married, and having lower levels of psychiatric severity. Among men, predictors of higher retention included being over age 40, receiving employer suggestions to enter treatment, and having abstinence goals. These findings suggest treatment factors that may enhance retention among insured populations (Mertens, & Weisner, 2000).

Treatment Retention: Interaction Effects of Client and Treatment Program Characteristic. The effects of treatment program and client characteristics on client retention were examined in data sets obtained from 59 drug abuse treatment programs and 3,764 patients who had discharge records. UCLA and the University of Southern California researchers analyzed the data separately for residential methadone maintenance and outpatient drug-free programs. A noteworthy significant interaction effect was the program's funding source and patient's gender on treatment retention in the outpatient drug-free modality. Female clients stayed in the programs that accepted only public funding for shorter periods than in programs that accepted both public and private funding. Male patients remained in treatment an average of 25.3 fewer days than female patients in programs that only accepted public funds, but stayed about the same time as females if the programs received mixed funding (Chou, Hser, & Anglin, 1998).

Voucher Incentives Promote Abstinence in Non-Treatment Seeking Female Cocaine Abusers: A Serendipitous Finding. Researchers at New York State Psychiatric Institute and the College of Physicians and Surgeons of Columbia University who had previously developed and reported on a laboratory model of "binge use" of cocaine that permitted characterization of behavior during the binge and during withdrawal from the binge, subsequently attempted to extend their model to a sample of high-use female cocaine abusers. Because of logistical difficulties associated with recruiting females for extended inpatient studies, the investigators used a modified protocol in which the withdrawal phase was conducted on an outpatient basis using a voucher procedure to facilitate abstinence so that withdrawal effects could be assessed. In the initial inpatient 4 to 5-day "binge" phase, ten non-treatment seeking females were permitted to smoke up to 6 doses of 50 mg cocaine base in two daily "binge" sessions for two consecutive days. Cocaine's subjective and cardiovascular effects were consistent with those previously reported in males, with the exceptions of a within-binge decrease in cocaine craving and a within-binge increase in tiredness among females. In the subsequent 2-week out-patient abstinent period, urine samples and questionnaire responses were collected daily and subjects received merchandise vouchers each time their urine sample contained less cocaine metabolite than the prior sample and was negative for all other drugs tested. Although session attendance was excellent (98%), during this 2-week abstinent phase, because only 56% of the urines indicated no new cocaine use, cocaine withdrawal effects could not be assessed. Nevertheless, achievement of 56% daily abstinence in a group of non-treatment seeking, high-use female cocaine abusers serendipitously points to the utility of using voucher incentives in this population. Smoked Cocaine Self-Administration in Females and Voucher Incentives for Abstinence (Evans, Levin, Fischman, & Foltin, 1998).

A Clinical Profile of Women with PTSD and Substance Dependence. Researchers at McLean Hospital in Belmont, Massachusetts compared the clinical characteristics of women with the dual diagnosis of Post Traumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD) and those with only PTSD to better understand why some women with PTSD also develop SUD while others do not. The dual diagnosis women consistently had a more severe clinical profile, including worse life conditions, more criminal behavior, and higher number of lifetime suicide attempts. One discrepant finding, however, was their lower rate of major depression. Interestingly, the two groups did not differ in number or type of lifetime traumas, PTSD onset or severity, family history of substance use, coping style, functioning level, psychiatric symptoms, or sociodemographic characteristics (Najavits, Weiss, & Shaw, 1999.

Prevention of Post-Rape Psychopathology. Epidemiological research indicates that rape victims are at risk of drug and alcohol abuse, posttraumatic stress disorder (PTSD), and major depression in addition to the stress generated by the forensic medical care routinely required within 72 hours post-assault if the women reports the crime to the policy. Researchers at the University of South Carolina have developed a hospital-based video intervention to minimize anxiety during forensic rape exams, and prevent post-rape posttraumatic stress disorder (PTSD), panic, and anxiety. Results of preliminary data indicate a strong relationship between psychological distress at the time of the exam and PTSD symptomatology 6 weeks post-rape. Preliminary data also indicate that the video intervention successfully reduced distress during forensic exams. In addition to preventing PTSD, panic and anxiety, this early care provides a unique opportunity to implement and evaluate an early intervention that could reduce development of drug and alcohol abuse and major depression (Resnick, Acierno, Holmes, Kilpatrick, & Jager, 1999).

Health Correlates of Sexual Violence in Homeless Women. The association of rape with specific health and substance use/abuse characteristics was examined in a sample of 974 homeless women in Los Angeles County. Researchers at RAND and UCLA administered structured interviews to women aged 15-44 who had spent at least one of the past 30 nights in non-traditional housing. Thirteen percent of the women reported being raped in the past year, and half of these women had been raped at least twice in the past year. Women reporting recent rape fared worse on every physical and mental health measure and were more likely to have a lifetime history of drug abuse or dependence and reports of recent drug use than other homeless women. These data indicate that sexual violence is a major problem confronting homeless women and that all homeless women who present with serious mental, physical, or substance abuse problems should be screened for violent experiences (Wenzel, Leake, & Gelberg, 2000).

Drug Treatment Effectiveness: The Effects of Gender and Ethnic Congruency and Client-Counselor Empathy. The effects of gender and ethnic congruency between patients and counselors on perceived counselor empathy, client engagement in treatment, and abstinence were examined in all 419 adult clients entering the 25 Los Angeles metropolitan outpatient drug treatment facilities between July and September in 1994. The data were analyzed by gender, ethnicity (African American, Latino, and White), and age (younger than 35 and 35 or older). Client-counselor gender and ethnic congruence were significantly associated with higher levels of perceived counselor empathy for all gender, ethnic, and age groups. Those congruencies had no effect on treatment engagement, but did impact abstinence in the 6 months prior to follow up in some groups. Client-counselor gender congruence improved abstinence in females, Latinos, and patients age 35 or older. Client counselor ethnic congruence improved abstinence only in females. For all subgroups, high client-counselor empathy was a greater predictor of abstinence than gender or ethnic congruence, with the exception of Latinos. The findings support a recommendation of paying closer attention to matching clients to counselors (Fiorentine, & Hillhouse, 1999).

Menstrual Cycle Phase Affects Smoking Withdrawal and Depressive Symptoms. Researchers at the University of Pittsburgh found that phase of the menstrual cycle affects withdrawal and depressive symptoms in women who attempt to quit smoking. In a study of 78 women enrolled in a smoking cessation trial, women who quit during the luteal phase of their cycle (day 15+ postmenstrual onset) had significantly more withdrawal symptoms and more depressive symptomatology during the week after quitting than women who quit during their follicular phase (days 1-14 postmenstrual onset). These data suggest that women seeking to quit smoking may reduce these adverse effects of cessation by choosing to quit during the follicular phase (Perkins, Levine, & Marcus, 2000).

Menstrual Cycle Phase Affects the Subjective Effect of d-Amphetamine. Laboratory-based research at the University of Chicago has shown that menstrual cycle phase is a factor in the subjective response to acute oral d-amphetamine. Sixteen healthy women received the drug during the follicular and mid-luteal phases of the menstrual cycle. Subjects reported a greater feeling of "high,Ó euphoria, energy, and intellectual efficiency during the follicular than the luteal phase, as well as more liking and wanting of the drug. During the follicular phase (when estrogen levels are high and progesterone levels are low), higher estrogen levels were associated with feeling energetic and intellectually efficient. During the luteal phase, when levels of both estrogen and progesterone are relatively high, the response to d-amphetamine was unrelated to estrogen level. These findings could have implications for consideration of menstrual cycle phase as a factor in protocols for the treatment of amphetamine dependence (Justice, & de Wit, 1999).

Limited Prosocial Information Exchange And Substance Use. Researchers at the University of Colorado at Boulder assessed attitudes, drug use, and mental health status in pregnant, inner-city residents, of whom 35 were substance abusers and 45 were nonusers. Structured interviews revealed that the users were more likely to report favorable attitudes toward drugs and polysubstance use, disengagement coping, depressive symptoms, negative affect, and antisocial behavior than were the nonusers. During videotaped interviews, trained observers coded less warmth and less prosocial information exchange (e.g., self-disclosure, question asking) among users. Analysis of coping strategies indicated that substance users were more likely that non-users to use asocial and antisocial coping. This study is the first to demonstrate an association between a substance-using lifestyle and limited prosocial information exchange. These findings could have implications for efforts to engage women in the treatment process (Blechman, Lowell, & Garrett, 1999).

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