Director's Report to Council - Research Findings Excerpts

February, 2005

Basic Neurosciences Research

Cannabinoids and Pregnancy

Ectopic pregnancy is a major reproductive health issue. Although other underlying causes remain largely unknown, one cause of ectopic pregnancy is embryo retention in the fallopian tube. In a recent study, Dr. Haibin Wang and his associates, Vanderbilt University of Medical Center, Nashville, TN, show that genetic or pharmacologic silencing of cannabinoid receptor CB1 causes retention of a large number of embryos in the mouse oviduct, eventually leading to pregnancy failure. This was reversed by isoproterenol, a beta-adrenergic receptor agonist. Impaired oviductal embryo transport is also observed in wild-type mice treated with methanandamide. Collectively, their results suggest that aberrant cannabinoid signaling impedes coordinated oviductal smooth muscle contraction and relaxation crucial to normal oviductal embryo transport. Colocalization of CB1 and beta2-adrenergic receptors in the oviduct muscularis implies that a basal endocannabinoid tone in collaboration with adrenergic receptor coordinates oviductal motility for normal journey of embryos into the uterus. Besides uncovering a new regulatory mechanism, this study could be clinically relevant to ectopic pregnancy. Wang, H., Guo, Y., Wang, D., Kingsley, P.J., Marnett, L.J., Das, S.K., DuBois, R.N. and Dey, S.K. Nature Medicine, 10, pp. 1074-1080, 2004.

Differences in Maternal Styles of Rearing May Predispose to or Protect Individuals From the Development of Addiction

While many people experiment with drugs, relatively few individuals develop a true addiction. Dr. Michael Meaney and his colleagues hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, they investigated whether stimulant- and stress-induced activation of nucleus accumbens dopamine transmission and dopamine-dependent behaviors might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non-handled) during the first 14 days of life. They found that, in comparison with their handled counterparts, maternally separated and non-handled animals are hyperactive when placed in a novel setting, display a dose-dependent higher sensitivity to cocaine-induced locomotor activity and respond to a mild stressor (tail-pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non-handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens-core and striatal dopamine transporter sites in maternally separated animals. They also found greatly reduced D3 dopamine receptor binding and mRNA levels in the nucleus accumbens-shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking. Brake, W.G., Zhang, T.Y., Diorio, J., Meaney, M.J. and Gratton, A. Influence of Early Postnatal Rearing Conditions on Mesocorticolimbic Dopamine and Behavioural Responses to Psychostimulants and Stressors in Adult Rats. European Journal of Neuroscience, 19, pp. 1863-1874, 2004.

Basic Behavioral Research

Sex Differences in the Escalation of Intravenous Cocaine Following Long- or Short-access to Self-administration

Drs. Megan Roth and Marilyn Carroll from University of Minnesota examined sex differences in the escalation of cocaine self-administration using a procedure similar to that previously reported with male rats (Ahmed and Koob, 1998;1999). This procedure is regarded as an animal model of the transition from drug use to addiction. Initially, rats were given access to cocaine either 6 hours/day (Long Access or LgA) or 1 hour/day (Short Access or Sh) for 21 days. This differential access phase was followed by a post-differential access phase in which all rats had 3 hours/day access to cocaine. As shown previously with male rats, Drs. Roth and Carroll found that for both sexes, in the differential access phase the LgA group self-administered more cocaine infusions than the ShA group. Moreover, they found that LgA females self-administered significantly more cocaine infusions than LgA males. In the post-differential-access phase in which all rats had 3 hours/day access to cocaine, and escalation from use to abuse was measured, LgA females self-administered more cocaine infusions than either LgA males, ShA males or ShA females. This study suggests that given opportunity, females will self-administer more than males and females are more sensitive than males to factors that contribute to the escalation of cocaine intake. Roth, M.E. and Carroll, M.E. Sex Differences in the Escalation of Intravenous Cocaine Intake Following Long- or Short-access to Cocaine Self-administration. Pharmacology, Biochemistry and Behavior, 78, pp. 199-207, 2004.

Behavioral and Brain Development Research

Interpersonal Maladjustment as Predictor of Mother's Response to Relational Parenting Intervention

This research team previously demonstrated that a Relational Psychotherapy Mothers' Group (RPMG) was more effective in improving parenting than standard drug counseling (DC) for mothers enrolled in methadone maintenance. The research team recently examined whether mother's interpersonal maladjustment predicted a differential response to RPMG in a sample of 52 mothers and 24 children ages 7 and 16 who had completed baseline, post-treatment, and 6-month follow-up assessments. Results indicated an interaction effect; as maternal interpersonal maladjustment increased, parenting problems improved for mothers in the RPMG group, but remained the same or worsened for DC mothers. Mothers' and children's reports of child maltreatment risk were in or near the normal range for RPMG mothers but in or near clinical range for DC mothers at post-treatment and follow-up. RPMG mothers reported improved affective interactions and the DC group reported no such improvements, regardless of mothers' level of interpersonal maladjustment. These findings highlight the importance of including parenting interventions in substance abuse treatment and the value of interpersonally oriented interventions for substance-abusing mothers and their children. Suchman, N.E., McMahon, T.J., and Luthar, S.S. Journal of Substance Abuse Treatment, 27, pp. 135-143, 2004.

Prenatal Cocaine: Quantity of Exposure and Gender Influences on School-Age Behavior

Investigators at Wayne State University have reported that both level of prenatal cocaine exposure and gender were significantly associated with school-age behavioral outcomes. Prenatal cocaine exposure was defined in two ways: dichotomous and ordinal. The dichotomous measure consisted of no exposure or any pregnancy exposure. The ordinal measure had three levels (none, some, persistent), with persistent prenatal exposure defined as continued cocaine use up until delivery as evidenced by positive maternal and/or infant urine testing at delivery. Data analyses were based on a total of 473 children, 204 of whom were prenatally exposed to cocaine; 24 of the cocaine-exposed children were classified as having persistent exposure. Behavior at 6 years of age was assessed using a teacher-report scale involving fourteen problem behavior areas. Boys with any prenatal cocaine exposure scored significantly higher (more problem behaviors) than non-exposed boys on the hyperactivity item. No similar cocaine effect was observed for girls. Boys, but not girls, with persistent exposure had more problems in central processing, motor skills, handling abstract concepts, and passivity to the environment. Covariates controlled for include prenatal exposure to alcohol and other illicit drugs, and postnatal drug use in the home. Delaney-Black, V., Covington, C., Nordstrom, B., et al. Prenatal Cocaine: Quantity of Exposure and Gender Moderation. Developmental and Behavioral Pediatrics, 25(4), pp. 254-263, 2004.

Prenatal Cocaine Exposure and Language Development

Recently-published results from two separate projects provide new information regarding associations between prenatal cocaine exposure and aspects of language development. From the University of Miami, Vogel and colleagues report that when the children in their study were 3 years old (424 children, 226 cocaine-exposed, 198 non-cocaine-exposed), there was a decrease in expressive language score with increasing level of prenatal cocaine exposure. Receptive language was more modestly, and not significantly, related to prenatal cocaine exposure. Using the same language assessment scale, the Clinical Evaluation of Language Fundamentals - Preschool (CELF-P), Lewis and co-investigators at Case Western Reserve University report that for their sample of 4-year-olds (189 cocaine-exposed and 185 non-cocaine-exposed), children exposed to cocaine in utero had poorer expressive and total language scores, and had more mild receptive language delays than nonexposed children. In both studies, the analyses took into account several key variables (e.g., prenatal exposures to alcohol, tobacco, and marijuana). Morrow, C.E., Vogel, A.L., Anthony, J.C., et al. Expressive and Receptive Language Functioning in Preschool Children with Prenatal Cocaine Exposure. Journal of Pediatric Psychology, 29(7), pp. 543-554, 2004; Lewis, B.A., Singer, L.T., Short, E.J., et al. Four-Year Language Outcomes of Children Exposed to Cocaine in Utero. Neurotoxicology and Teratology, 26(5), pp. 617-627, 2004.

In Utero Marijuana Exposure Associated with Abnormal Amygdala Dopamine D2 Gene Expression in the Human Fetus

Dr. Yasmin Hurd and her colleagues, using in situ hybridization histochemistry, have published the first description of neurobiological effects of in utero exposure to cannabis in the human fetus. Their results demonstrate that cannabis exposure during prenatal development causes a decrease in dopamine D2 mRNA expression in the amygdala and that the magnitude of this decrease was positively correlated with the level of exposure. Importantly, this decrease in D2 mRNA was gender-specific, occurring in males but not in females. This alteration in the mesocorticolimbic dopaminergic brain circuitry during development may contribute to the emotional and cognitive deficits that have been reported in children prenatally exposed to cannabis. Wang, X., Dow-Edwards, D., Anderson, V., Minkoff, H., Hurd, Y.L. Biological Psychiatry 56, pp. 909-915, 2004.

Sensation Seeking and Symptoms of Disruptive Disorder: Association with Nicotine, Alcohol, and Marijuana Use in Early and Mid-Adolescence

This cross-sectional study examined the association of Sensation Seeking (SS) and symptoms of Disruptive Disorders and investigated the associations of each with the risk of nicotine, alcohol, and marijuana use in a sample of 127 boys and 81 girls aged 11-14 years recruited from child psychiatry, pediatric adolescent, and pediatric family clinics. Results indicated that sensation seeking was correlated with Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD), however, when analyzed by gender, there was a significant correlation between SS and CD for boys, but no significant correlations between Sensation Seeking and any of the Disruptive Disorders for girls. Sensation seeking was associated with nicotine, alcohol, and marijuana use; ODD was associated with nicotine use; and Conduct Disorder was associated with alcohol and marijuana use for boys and girls, and smokeless tobacco use for boys. Results from a series of gender specific regression analyses found that SS and ODD predicted nicotine use by girls and SS and CD predicted alcohol and marijuana use by boys. For all other analyses of cigarette, alcohol, and marijuana use, SS was the only significant predictor. Measurement of Sensation Seeking and symptoms of Disruptive Disorder in clinic setting can help identify and characterize youth who are at increased risk for drug use during early and mid-adolescence. Martin, C.A., Kelly, T.H., Rayens, M.K., Brogli, B., Himelreich, K., Brenzel, A., Bingcang, C.M., and Omar, H. Psychological Reports, 84, pp. 1075-1082, 2004.

Depression, Negative Self-Image, and Suicidal Attempts as Effects of Substance Use and Substance Dependence

This study examined the degree to which cocaine/crack, marijuana, and alcohol use and dependence from 26.5 to 37 years of age predicted depression, negative self-image, negative personal outlook, and suicidal attempts by age 37 in an inner-city sample of 277 African American men and women. Results from this sample, derived from the National Collaborative Perinatal Project (NCPP), found that substance use and dependence predicted mental health outcomes, controlling for prior depression, psychiatric treatment, and suicide attempts and that these predictions differed by gender. Overall, measures of substance use and dependence demonstrated relatively more predictions of suicide attempts for the men and negative self-image and negative personal outlook for the women. For the female sample, making a suicide attempt was predicted by cocaine/crack use and substance dependence, number of suicide attempts was predicted by cocaine/crack use, and depression was predicted by marijuana use. Negative self-image was predicted by substance use, illicit drug use, and substance dependence, and negative personal outlook was predicted by cocaine/crack use, substance use, and illicit drug use. For the male sample, making a suicide attempt was predicted by illicit drug use and substance use, number of suicide attempts was predicted by cocaine/crack use, illicit drug use, substance use, and substance dependence, and depression was predicted by illicit drug use. Negative personal outlook was predicted by cocaine/crack use, substance use, and substance dependence. There were no significant predictors of negative self-image for males. This study highlights gender differences in the important role of substance use in mental health outcomes. Friedman, A.S., Terras, A., Zhu, W. and McCallum, J. Journal of Addictive Diseases, 23(4), pp. 55-71, 2004.

Epidemiology ad Etiology Research

Cigarette Access for Minors Has Been Declining, But Remains High

Investigators from the Monitoring the Future Study examined trends in middle and high school students' perceived ease, methods, and locations of access to cigarettes, and assessed differences related to their sociodemographic characteristics and smoking status. Annual data from nationally representative samples of 8th-, 10th-, and 12th-grade students were analyzed for the 1997-2002 period. Analyses revealed that perceived ease of access decreased significantly among never and past smokers. Decreased individual purchasing in retail outlets, as well as decreased purchasing from vending machines, were reported by 8th- and 10th-grade students. All grades reported decreased purchasing from self-service placements of cigarettes. Decreases in access were not reported across all retailer types, and no significant increases were seen in the percent of underage purchasers who reported being asked to show identification. Both gender and ethnicity were significantly related to where and how underage youth reported obtaining cigarettes. Findings show that: (1) cigarette access for minors has been declining, but remains high; (2) perceived access to cigarettes clearly increases with level of smoking; and (3) policies to reduce such access may be having an impact as evidenced by decreased retail and vending machine purchases and self-service purchases. The authors conclude that states should continue to strengthen efforts to reduce youth cigarette access, especially in the areas of confirming buyer age via identification checks, and should make efforts to decrease access across all retailer types. Johnston, L.D., O'Malley, P.M., and Terry-McElrath, Y.M. Methods, Locations, and Ease of Cigarette Access for American Youth, 1997-2002. American Journal of Preventive Medicine, 27, pp. 267-276, 2004.

Parenting Practices: A Test of Gender Differences and Four Theoretical Perspectives

The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth and more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting. Locke, T.F. and Newcomb, M.D. Child Maltreatment, Parent Alcohol- and Drug-related Problems, Polydrug Problems, and Parenting Practices: A Test of Gender Differences and Four Theoretical Perspectives. Journal of Family Psychology, 18, pp. 120-134, 2004.

Child Maltreatment, Parent Alcohol- and Drug-related Problems, Polydrug Problems, and Parenting Practices: A Test of Gender Differences and Four Theoretical Perspectives

The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth and more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting. Locke, T.F. and Newcomb, M.D. Child Maltreatment, Parent Alcohol- and Drug-related Problems, Polydrug Problems, and Parenting Practices: A Test of Gender Differences and Four Theoretical Perspectives. Journal of Family Psychology, 18, pp. 120-134, 2004.

Psychosocial Antecedents of Injection Risk Reduction

This study is based on a collaboration with the Integrated Substance Abuse Program at UCLA. In this study, the authors used the AIDS Risk Reduction Model (ARRM) to test a mediated stage-based longitudinal structural equation model analyzing the impact of intention to change injection risk behaviors on 6-month outcomes in a sample of 294 HIV-negative opiate addicted individuals currently in treatment. The ARRM predicts less occurrence of AIDS risk behaviors through a three-stage process: (1) perceiving one's behavior as risky and recognizing one's skills to reduce the behavior, (2) forming an intention to change behavior, and (3) acting on that intention. Stage 1 ARRM constructs of AIDS knowledge, susceptibility, fear of AIDS and Peer Norms were hypothesized to predict Stage 1 end points of perceived risk, response efficacy, and self-efficacy as well as baseline risk behavior. These constructs predicted Stage 2 (intended risk reduction) which, in turn, predicted the Stage 3 outcome of injection risk behaviors. Prior behavior, continuous participation in treatment, and the effect of gender were also included in the model. Intended risk reduction and continuous participation in treatment significantly predicted less injection risk behavior at Stage 3. Stage 1 constructs of greater self-efficacy, less baseline risk behavior, less susceptibility and greater fear of AIDS predicted intentions to reduce risk as did female gender. Leverage points for change in this highly vulnerable population are discussed in the article. Longshore, D., Stein, J.A. and Conner, B.T. Psychosocial Antecedents of Injection Risk Reduction: A Multivariate Analysis. AIDS Education and Prevention 16, pp. 53-66, 2004.

Mate Similarity for Substance Dependence and Antisocial Personality Disorder

Substance dependence (SD) and antisocial personality disorder (ASPD) are highly comorbid and aggregate in families. Mating assortment may be an important process contributing to this familial aggregation. Authors hypothesized that symptom counts of substance dependence, antisocial personality disorder, and retrospectively assessed conduct disorder (CD) would be correlated significantly among parents of youth in treatment for substance use and conduct problems and, separately, among parents of community controls. Authors examined SD, ASPD, and CD among 151 pairs of parents of adolescents in treatment for substance use and conduct problems, and in 206 pairs of parents of control subjects. For average dependence symptoms (ADS) (the sum of across-drug substance dependence symptoms divided by the number of substance categories meeting minimum threshold use) mother-father correlations were 0.40 for patients and 0.28 for controls. Mother-father correlations for ASPD symptom count were 0.33 for patients and 0.26 for controls and for CD symptom count were 0.31 for patients and 0.10 for controls. Spousal correlations for ADS and ASPD, suggest substantial non-random mating. Results support gender differences in homogamy for SD. Behavior genetic studies of these disorders need to account for assortment to avoid biases in estimates of genetic and environmental effects. Sakai, J.T., Stallings, M.C., Mikulich-Gilbertson, S.K., Corley, R.P., Young, S.E., Hopfer, C.J. and Crowley T.J. Drug and Alcohol Dependence, 16, pp. 165-175, 2004.

Defining Nicotine Dependence for Genetic Research: Evidence from Australian Twins

The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and male twins. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerstrom Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers. Results showed that phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of 'giving up or reducing important activities in order to smoke', which was weakly familial. The findings suggest that the salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men. Lessov, C.N., Martin, N.G., Statham, D.J., Todorov, A.A., Slutske, W.S., Bucholz, K.K., Heath, A.C., and Madden, P.A. Psychological Medicine, 34, pp. 865-879, 2004.

Epidemiology of Inhalant Use, Abuse, and Dependence among Youth

Secondary analysis of data on adolescents aged 12-17 from 2000 and 2001 National Household Surveys on Drug Abuse found that inhalant use was common. Results showed that 0.4% of adolescents met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youth with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school-age children. Wu, L.T., Pilowsky, D.J., and Schlenger, W.E. Inhalant Abuse and Dependence among Adolescents in the United States. J Am Acad Child Adolesc Psychiatry, 43, pp. 1206-1214, 2004.

Pathways From Physical Childhood Abuse To Partner Violence In Young Adulthood

Analyses investigated several competing hypotheses about developmental pathways from childhood physical abuse and early aggression to intimate partner violence (IPV) for young adult males and females at age 24. Potential intervening variables included: adolescent violence (age 15 to 18), negative emotionality at age 21, and quality of one's relationship with an intimate partner at age 24. At the bivariate level, nearly all variables were associated in the expected directions. However, tests of possible intervening variables revealed only a few significant results. For males, a strong direct effect of abuse on later partner violence was maintained in each model. For females, the quality of one's relationship with an intimate partner did appear to mediate the effect of childhood abuse on later violence to a partner, raising the possibility of gender differences in developmental pathways linking abuse to IPV. Herrenkohl, T.I., Mason, W.A., Kosterman, R., Lengua, L.J., Hawkins, J.D. and Abbott R.D. Violence and Victims, 19, pp. 123-136, 2004.

Religious Activity and Risk Behavior Among African American Adolescents

This study examines how religious activity is associated with risk behaviors, concurrently and developmentally among urban African American adolescents. Seven hundred and five African American youths were interviewed annually during high school. Retention rates for the study exceeded 90%. Frequency of religious activity, sexual intercourse, and alcohol, cigarette, and marijuana use were assessed at each wave. Growth curve analyses found negative concurrent associations between religious activity and each of the four risk behaviors. The developmental effects of religious activity varied by gender. Higher levels of religious activity in 9th grade predicted smaller increases in marijuana use among males and cigarette use among females. In addition, larger decreases in religious activity during high school were associated with greater increases in alcohol use among males and sexual intercourse among females. During high school, religious activity limits the development of certain types of risk behavior among African American youth, even after controlling for reciprocal effects. Steinman, K.J., and Zimmerman M.A. Religious Activity and Risk Behavior among African American Adolescents: Concurrent and Developmental Effects. Am J Community Psychol., 33, pp. 151-161, 2004.

An HIV Prevalence-Based Model for Estimating Urban Risk Populations of IDUs and MSM

Issues of cost and complexity have limited the study of the population size of men who have sex with men (MSM) and injection drug users (IDUs), two groups at clearly increased risk for human immunodeficiency virus (HIV) and other acute and chronic diseases. In this study, researchers developed a prototypical, easily applied estimation model for these populations and applied it to Miami, Florida. This model combined HIV prevalence estimates, HIV seroprevalence rates, and census data to make plausible estimates of the number and proportion of MSM and IDUs under a number of assumptions. Sensitivity analyses were conducted to test the robustness of the model. The model suggests that approximately 9.5% (plausible range 7.7%-11.3%) of Miami males aged 18 years or older are MSM (point estimate, N = 76,500), and 1.4% (plausible range 0.9%-1.9%) of the total population aged 18 years or older are IDUs (point estimate, N= 23,700). Males may be about 2.5 times more likely than females to be IDUs. The estimates were reasonably robust to biases. The model was used to develop MSM and IDU population estimates in selected urban areas across Florida and should be replicable in other medium-to-large urban areas. Such estimates could be useful for behavioral surveillance and resource allocation, including enhanced targeting of community-based interventions for primary and secondary HIV prevention. Lieb, S., Friedman, S., Zeni, M., Chitwood, D., Liberti, T., Gates, G., Metsch, L., Maddox, L., and Kuper, T. An HIV Prevalence-Based Model for Estimating Urban Risk Populations of IDUs and MSM. J Urban Health, 81, pp. 401-415, 2004.

The Association of Sexual Dysfunction and Substance Use among a Community Epidemiological Sample

This study examines the prevalence of DSM-III sexual dysfunctions and their association with comorbid drug and alcohol use in a community epidemiologic sample. The data for these analyses are based on the Epidemiological Catchment Area Project, a multistage probability study of the incidence and prevalence of psychiatric disorders in the general population conducted in 1981-83. Only the sample of 3,004 adult community residents in the St. Louis area was queried on DSM-III sexual dysfunctions of inhibited orgasm, functional dyspareunia (painful sex), inhibited sexual excitement (i.e., lack of erection/arousal), and inhibited sexual desire. There was a prevalence rate of 11% for inhibited orgasm, 13% for painful sex, 5% for inhibited sexual excitement, 7% for inhibited sexual desire, and 26% for any of these sexual dysfunctions (14% for men and 33% for women). The prevalence of qualifying lifetime substance use among the population was 37%, with males meeting more drug and alcohol use criteria than females. After controlling for demographics, health status variables, and psychiatric comorbidity (depression disorder, generalized anxiety disorder, antisocial personality disorder, and residual disorders), inhibited orgasm was associated with marijuana and alcohol use. Painful sex was associated with illicit drug use and marijuana use. Inhibited sexual excitement was more likely among illicit drug users. Inhibited sexual desire was not associated with drug or alcohol use. Johnson, S.D., Phelps, D.L. and Cottler, L.B. Archives of Sexual Behavior, 33, pp. 55-63, 2004.

Males at Greater Risk for Violence, Females Higher Risk of PTSD

This study estimated the cumulative occurrence of traumatic events and posttraumatic stress disorder (PTSD), using fourth edition (DSM-IV) criteria, in a high-risk sample of young people in urban United States. The epidemiological sample (n = 2,311) was recruited in 1985-1986 at entry into first grade of a public school system of a large mid-Atlantic city. Participants were interviewed about history of trauma and PTSD in 2000-2002 when their mean age was 21 years (n = 1,698). The authors found that the lifetime occurrence of assaultive violence was 62.6% in males and 33.7% in females. The risk of assaultive violence in males (but not females) varied by childhood area of residence within the city; the occurrence of other traumas did not vary by area of childhood residence. Females had a higher risk of PTSD than males following assaultive violence (odds ratio = 4.0, 95% confidence interval 2.0-8.3), but not following other traumas. A comparison of the results from this largely inner-city sample with the results from a recent study of a largely suburban sample in another region of the United States in which the same criteria and measures of trauma and PTSD were used suggested the possibility that males' risk for assaultive violence and females' risk for PTSD following exposure to assaultive violence might vary by characteristics of the social environment. Breslau, N., Wilcox, H.C., Storr, C.L., Lucia, V.C., and Anthony, J.C. Trauma Exposure and Posttraumatic Stress Disorder: A Study of Youths in Urban America. J Urban Health, 81, pp. 530-544, 2004.

Life Transitions Predict Depression and Alcohol Use

This study examined longitudinally the relationship between depressive symptoms and alcohol use in a sample of black youth. Participants were 458 black males and females interviewed annually during the high school years and then for 3 years during the transition to adulthood. The relationship was examined using growth curves with Hierarchical Linear Modeling. The results suggest that depressive symptoms decrease over time, whereas the use of alcohol increases. The findings also suggest that youths use alcohol as a way to cope with depressive symptoms and that males are more likely to use alcohol as self-medication. The results also indicate that changes in alcohol use do not predict depressive symptoms, but that life changes associated with the transition to adulthood, such as attending college, predict changes in depressive symptoms and alcohol use. Findings highlight the role of depressive symptoms for predicting alcohol use among black youth and the role of significant life transitions in altering the pattern of alcohol use presented previously by these youths. Repetto, P.B., Zimmerman, M.A., and Caldwell, C.H. A Longitudinal Study of the Relationship between Depressive Symptoms and Alcohol Use in a Sample of Inner-city Black Youth. J Stud Alcohol., 65, pp. 169-178, 2004.

Greater Opportunity to Buy Illegal Drugs in Disadvantaged Neighborhoods

This study investigated whether subgroups of people living in disadvantaged neighborhoods may be more likely to come into contact with drug dealers as compared with persons living in more advantaged areas, with due attention to male-female and race-ethnicity differences. The study used standardized survey data collected using stratified, multistage area probability sampling with a nationally representative sample of household residents age 12 or older (n = 25,500). Evidence supports an inference that women are less likely to be approached by someone selling illegal drugs. The study found no more than modest and generally null racial and ethnicity differences, even for residents living within socially disadvantaged neighborhoods, where chances to buy illegal drugs are found to be more common. Limitations of survey data always merit attention, but this study evidence lends support to the inference that physical and social characteristics of a neighborhoods can set the stage for opportunities to become involved with drugs. Storr, C.L., Chen, C.Y., and Anthony, J.C. "Unequal Opportunity": Neighborhood Disadvantage and the Chance to Buy Illegal Drugs. J Epidemiol Community Health, 58, pp. 231-237, 2004.

Course and Psychosocial Correlates of Personality Disorder Symptoms in Adolescence

Personality disorder symptoms were investigated in a community sample of young people (n=714) to assess their relationship over time with well-being during adolescence and the emergence of intimacy in early adulthood. Drawing on Erikson's theory of psychosocial development, changes in adolescent well-being were conceptualized as indirect indicators of identity consolidation. Cluster B personality disorder symptoms (borderline, histrionic, and narcissistic symptoms) were conceptualized to represent "identity diffusion" - i.e., maladaptive personality traits that usually resolve during the identity crisis of adolescence. Latent growth models were used in two age cohorts to assess (1) interrelationships between Cluster B symptoms, well-being, and intimacy at mean ages 13.8 and 18.6 years; and (2) associations between their developmental trajectories over the next 6 years. As expected, higher personality disorder symptoms were associated with lower well-being during adolescence, and declines in personality disorder symptoms over time were associated with corresponding gains in well-being. Consistent with Erikson's developmental theory, there was an inverse relationship between Cluster B symptoms and intimacy that increased in strength as young people entered adulthood. As an indicator of successful identity consolidation, well-being was significantly associated with intimacy in female adolescents and young adults. Crawford, T.N., Cohen, P., Johnson, J.G., Sneed, J.R., and Brook, J.S. The Course and Psychosocial Correlates of Personality Disorder Symptoms in Adolescence: Erikson's Developmental Theory Revisited. Journal of Youth and Adolescence, 33, pp. 373-387, 2004.

Risk and Protective Factors related to Physical Violence Against Impoverished Women

Violence represents a significant threat to the health of impoverished women. Few studies have examined what characteristics might be associated with increased risk of violence or protection from physical violence directed at such women, although this information is important in informing violence prevention and intervention efforts. According to the authors, this is the first study that has prospectively examined, in representative probability samples of impoverished women, multiple risk and protective factors to understand their relative importance to physical victimization. Study participants were 810 women in Los Angeles County, 402 in shelters and 408 in Section 8 low-income housing, who completed structured interviews at baseline and 6-month follow-up. Significant (p < .05) multivariate predictors of physical violence experienced during the 6 months prior to follow-up interview were physical or sexual violence experienced as a child, physical violence experienced during the 6 months prior to baseline interview, having multiple sexual partners, psychological distress, and poor social support. Results of this study highlight the persistence of physical violence in the lives of impoverished women and plausible, prospective risk factors for this violence. Findings also highlight opportunities to reduce women's risk of experiencing violence through enhancing women's social support and mental health. Wenzel, S.L., Tucker, J.S., Elliott, M.N., Marshall, G.N., and Williamson, S.L. Physical Violence Against Impoverished Women: A Longitudinal Analysis of Risk and Protective Factors. Women's Health Issues, 14, pp. 44-54, 2004.

The Co-occurrence of Violence, Substance Use and Disorder, and HIV-Risk Behavior among Sheltered and Low-income Housed Women in Los Angeles County

Violence against women, substance use and disorder, and HIV represent three significant threats to the health of women, yet little is known about the extent of these epidemics among indigent women. This study investigates and documents differences in the prevalence and co-occurrence of physical and sexual violence, substance use and disorder, and HIV risk behavior in sizable probability samples of sheltered homeless and low-income housed women. Retrospective self-reports were obtained through structured interviews with stratified random samples of women residing in shelters (N = 460) and low-income housing (N = 438) in Los Angeles County, California. Results indicated that sheltered women were more likely than housed women to report experiencing physical and sexual violence, substance use and disorder, HIV risk behavior, and co-occurrence of these problems in the past year. Differences remained when propensity weights were used to equate the groups on demographic and background characteristics. Findings suggest remarkable need for services among communities of indigent women. Higher rates of problems among women in shelters highlight the importance of differentiating among subgroups of indigent women in community-based prevention and intervention activities and tentatively suggest a protective influence of housing. Wenzel, S.L., Tucker, J.S., Elliott, M.N., Hambarsoomians, K., Perlman, J., Becker, K., Kollross, C., Golinelli, D. Prevalence and Co-occurrence of Violence, Substance Use and Disorder, and HIV Risk Behavior: A Comparison of Sheltered and Low-income Housed Women in Los Angeles County. Prev Med., 39, pp. 617-624, 2004.

Child Sexual Abuse and HIV: An Integrative Risk Reduction Approach

In recent years, researchers have noted a significant association between child sexual abuse (CSA) and HIV. This association has important implications for HIV prevention and intervention. First, the fact that women who contract HIV are more likely to have been sexually abused as children suggests a continuum of victimization, such that early victimization may confer greater sexual risk-taking and likelihood of revictimization, resulting in HIV infection. Thus, the possible pathways between CSA and HIV need to be elucidated in order to prevent further negative outcomes. Second, the implications for HIV research and intervention are significant. Sexual abuse during childhood is associated with disturbances in the self that pervade an individual's development, and these disturbances are likely to maintain HIV risk behaviors unless ameliorated. Therefore, individuals who are HIV-positive and have a history of child sexual abuse may face "double jeopardy" for negative outcomes, including additional risks for reinfection, sexual revictimization, physical impairment, and non-adherence to HIV treatment that are beyond those associated with HIV infection. Intervention approaches for HIV-positive women with sexual abuse histories need to consider pathways of risk, ameliorate the disruptions in development that result from CSA, and address the additional additive and interactive influences of HIV and CSA on health outcomes. This chapter presents a brief overview of the consequences of CSA that may lead to higher risk for HIV, offers a critique of early intervention paradigms, and presents an integrative risk-reduction approach for HIV-positive women with CSA histories, currently in clinical trial, that addresses the link between CSA and HIV in a developmental and cultural context. Finally, preliminary findings from the intervention and implications for future directions are discussed. Chin, D., Wyatt, G., Carmona, J. V., Loeb, T.B., and Myers, H. Child Sexual Abuse and HIV: An Integrative Risk Reduction Approach. In L. Koenig, A. O'Leary, L. Doll, and Pecquegnat, (Eds.), From Child Sexual Abuse to Adult Sexual Risk: Trauma, Revictimazation, and Intervention, pp. 233-250. Washington D.C.: American Psychological Association, 2004.

Adolescent Predictors of Young Adult and Adult Alcohol Involvement and Dysphoria in a Prospective Community Sample of Women

The adolescent predictors of later alcohol involvement (AI), dysphoria (D), and their shared association (AD) among women have not been adequately established. Three waves of data from an ethnically diverse community sample of women, assessed over 16 years are used to study how various psychosocial factors in adolescence influenced later drinking, depression, and their shared association. Structural equation models revealed that several adolescent ecodevelopmental and social development model variables influenced their later outcome in young adulthood and adulthood. The strongest relation was between adolescent Social Conformity and adult AD (b = -.46) over a 16-year period, emphasizing the impact of this construct. Numerous other relations were revealed. For instance, less satisfaction with school during adolescence predicted adult AI. Having a good bond to the family in adolescence predicted a lower quantity of alcohol consumed during adulthood. Lower satisfaction with "what you want to be" during adolescence predicted young adult D. Higher levels of adolescent relationship satisfaction and school satisfaction predicted less suicidal ideation as an adult. Prevention interventions focusing on increasing socially conforming attitudes and on strengthening relationships both in and out of the home during adolescence are likely to be effective in reducing aspects of AI, D, and AD for women in the general community. Locke, T. F., and Newcomb, M.D. Adolescent Predictors of Young Adult and Adult Alcohol Involvement and Dysphoria in a Prospective Community Sample of Women. Prevention Science, 5, pp. 151-168, 2004.

Tobacco Smoking and Depressive Symptomatology

Whereas an association between cigarette smoking and depression has been established in Anglo populations, replication of tobacco-depression associations in countries where smoking is growing may provide important new insights. The objectives of this study were to estimate the association of depressive symptomatology with tobacco smoking, number of cigarettes smoked daily, and smoking cessation in a representative sample of the Mexican population. The data come from the Third National Addictions Survey (1998) conducted by the Mexican Ministry of Health, representative of Mexico's civilian population residing in cities and towns with 2500+ inhabitants, aged 18-64. Part of a multi-stage, stratified, probability sample, 1935 men and women answered a version of the survey that also included the CES-D depression scale. Analyses addressed the survey's complex design and controlled for income and educational level. The results showed that, among women only, current smokers had twice the odds of elevated depressive symptomatology than never smokers (OR 2.1, 95% CI 1.3-3.5, p = 0.002). For men, only those smoking a pack or more a day had greater odds of depressive symptomatology (OR 5.9, 95% CI 1.6-21.9, p = 0.008). Overall, former smokers who ceased smoking within 6 months had lower odds of depressive symptomatology than current smokers (OR 0.4, 95% CI 0.1-1.0, p = 0.042). These findings add to the accumulating evidence for the association between smoking and depression in different cultures and populations. Benjet, C., Wagner, F.A., Borges, G.G., and Medina-Mora, M.E. The Relationship of Tobacco Smoking with Depressive Symptomatology in the Third Mexican National Addictions Survey. Psychol Med, 34, pp. 881-888, 2004.

Age at First Use and Psychopathology as Risk Factors for Substance Use Disorder

This paper explores the issue of early drug use as a risk factor for adolescent substance use disorder (SUD), and the possible role of comorbid conduct problems in explaining this association. Sophisticated statistical tests were applied to longitudinal data from a large population-based sample, the Great Smoky Mountains Study, assessed annually between ages 9 and 16. Of note, drug use before age 13 was a strong predictor of transition to SUD, and early use remained a risk factor even in the absence of conduct disorder. Boys with a history of depression were at increased risk for SUD, and girls with anxiety experienced an increased risk at age 16. Findings from such large population-based studies can help target populations at higher risk for drug abuse for appropriate preventive interventions. Sung, M., Erkanli, A., Angold, A., and Costello, E.J. Effects of Age at First Substance Use and Psychiatric Comorbidity on the Development of Substance Use Disorders. Drug and Alcohol Dependence, 75, pp. 287-299, 2004.

Neurobehavior Disinhibition in Childhood Predicts Suicide Potential and Substance Use Disorder by Young Adulthood

The objectives of this study were to (1) determine whether two factors that are established components of the risk for substance use disorder (SUD) also impact on the risk for suicide; and (2) evaluate whether SUD manifest by early adulthood predicts suicide propensity. Neurobehavior disinhibition assessed in 227 boys at ages 10-12 and 16 and parental history of SUD were prospectively evaluated to determine their association with the risk for SUD and suicide propensity between ages 16 and 19. The results indicated that neurobehavior disinhibition at age 16 predicts suicide propensity between ages 16 and 19 (p = .04). A trend was observed (p = .08) for SUD manifest between ages 16 and 19 to predict suicide propensity during the same period. Maternal SUD is directly associated with son's SUD risk but not suicide propensity. Paternal SUD predicts son's neurobehavior disinhibition that, in turn, predisposes to SUD. A direct relation between paternal SUD and son's suicide propensity was not observed. These findings suggest that neurobehavior disinhibition, a component of the liability of SUD, is also associated with suicide risk. These results are discussed within a neurobehavioral framework in which prefrontal cortex dysfunction is hypothesized to underlie the risk for these two outcomes. Tarter, R.E., Kirisci, L., Reynolds, M., and Mezzich, A. Drug and Alcohol Dependence 76, S45-S52, 2004.

Prevention Research

Preventing Substance Use and Disordered Eating

This article assesses the efficacy of a school-based, sport team-centered program to prevent young female high school athletes' disordered eating and body-shaping drug abuse. The ATHENA (Athletes Targeting Healthy Exercise and Nutrition Alternative) curriculum's 8 weekly 45-minute sessions were incorporated into a team's usual practice activities. Content was gender-specific, peer-led, and explicitly scripted. Experimental athletes reported significantly less ongoing and new use of diet pills and less new use of athletic-enhancing substances (amphetamines, anabolic steroids, and sport supplements). Other health-harming actions were also reduced (e.g., riding with an alcohol-consuming driver, failure to use seat belts, and new sexual activity). ATHENA athletes had positive changes in strength-training, self-efficacy and healthy eating behaviors. Thus, sport teams are effective natural vehicles for gender-specific, peer-led curricula to promote healthy lifestyles and to deter disordered eating, athletic-enhancing substance use, and other health-harming behaviors. Elliot, D.L., Goldberg, L., Moe, E.L., DeFrancesco, C.A., Durham, M.B., and Hix-Small, H. Preventing Substance Use and Disordered Eating: Initial Outcomes of the ATHENA (Athletes Targeting Health Exercise and Nutrition Alternatives) Program. Archives of Pediatric Adolescent Medicine, 158, pp. 1043-1049, 2004.

Predicting Marijuana Use Cessation 5 years after Continuation High School

Cessation from marijuana use five years after completion of continuation high school was predicted by social, attitude, intrapersonal, violence-related, drug use, and demographic baseline measures from 339 high risk teenage marijuana users. Young adult social roles were included as additional predictors. Quitting was defined as no use of marijuana in the last 30 days (42% of the sample at follow-up). Results indicate that baseline level of marijuana use, male gender, young adult marital status, and friends' marijuana use (marginal) remained significant direct predictors of quitting. These results suggest the need to reduce psychological dependence on marijuana and increase social unacceptability of marijuana use across genders to increase prevalence of quit attempts. Sussman, S. and Dent, C.W. Five-Year Prospective Prediction of Marijuana Use Cessation of Youth at Continuation High Schools. Addictive Behaviors, 29(6), pp. 1237-1243, 2004.

Adolescent Depression and Suicide Risk Are Associated with Sex and Drug Use Behavior

Although both depression and suicide in adolescents have been associated with drug use and early sexual intercourse, the relationship has not been systematically studied in a nationally representative sample. Sixteen patterns of combined sex and drug use behaviors were obtained through analysis of responses to Wave I of the National Longitudinal Study of Adolescent Health conducted from September 1994 through December 1995. Analyses tested correlations between behavior patterns and current depression, serious suicidal ideation, and previous suicide attempt, controlling for gender, race/ethnicity, family structure, and parent education. Compared to youth who abstain from risk behaviors, involvement in any drinking, smoking, and/or sexual activity was associated with significantly increased chances of depression, suicidal ideation, and suicide attempts. These problems were highest among youth who engaged in illegal drug use. There were few differences between boys and girls who abstain from sex and drug behaviors. Girls were less likely than boys to engage in high-risk behaviors, but those who did tended to be more vulnerable to depression, suicidal ideation, and suicide attempt. Hallfors, D.D., Waller, M.W., Ford, C.A., Halpern, C.T., Brodish, P.H., and Iritani, B. Adolescent Depression and Suicide Risk - Association with Sex and Drug Behavior. Am J of Preventive Med., 27(3), pp. 224-231, 2004.

Self-esteem and Alcohol Use

Prior studies have found inconsistent relationships between measures of self-concept and adolescent alcohol use. This study explored whether the link between various measures of self-concept and alcohol use depends on gender and whether negative rather than positive self-esteem (i.e., self-derogation) might be more useful in predicting alcohol use. Students (N = 1459) attending 22 middle and junior high schools in New York City completed surveys that included measures of efficacy, self-derogation, and alcohol use. Participants completed surveys at baseline, 1-year follow-up, and 2-year follow-up. Findings indicate that lower efficacy was related to greater self-derogation a year later across gender. Increased self-derogation predicted higher alcohol use for girls but not boys. These findings are congruent with a literature highlighting the importance of negative thoughts about the self in drinking behavior for women but not men. Epstein, J.A., Griffin, K.W. and Botvin, G.J. Efficacy, Self-derogation, and Alcohol Use among Inner-city Adolescents: Gender Matters. Journal of Youth & Adolescence, 33, pp. 159-166, 2004.

Influence of Parents on Child Anti-social Behavior

This study examined the unique influence of mothers and fathers on their children's antisocial behavior using a sample of 325 families with sixth grade children. Multiple-group comparisons were conducted to identify differences in the relationships for mothers and fathers with daughters versus sons. Results suggested that, while the relationships were often similar for both parents and for both daughters and sons, mothers and fathers uniquely influenced their child's antisocial behavior depending on the child's gender. Overall, cross-gender influence appeared to be particularly important for fathers' control of their daughters' antisocial behavior. Kosterman, R., Haggerty, K.P., Spoth, R. and Redmond, C. Unique Influence of Mothers and Fathers on their Children's Antisocial Behavior: A Social Development Perspective. Journal of Marriage and Family, 66(3), pp. 762-778, 2004.

Early Intervention Reduces Marijuana Use and Psychopathology in Recent Rape Victims

Nearly 700,000 adult women are raped annually although only one in seven reports the assault to police and receive forensic exams and other professional services. The forensic exam, nevertheless, provides a unique opportunity for a preventive intervention to aid women to cope with potential stress related to the rape-exam procedures and address potential post-rape psychopathology. The intervention implemented with 205 adolescent and adult (15 years and older) female rape victims involved a 17-minute videotape that both explains the forensic exam procedures and uses a cognitive-behavioral approach to reduce anxiety and subsequent PTSD versus standard post-rape treatment control. Sixty percent of the women provided 6-week follow up data. Results indicate that at 6-weeks post exam marijuana use was significantly lower in the video intervention group but that there were no significant differences in rates of abusing alcohol or other drugs. The data also found that the video intervention helped women with a prior assault more than those with no prior assault. Resnick, H., Acierno, R., Kilpatrick, D.G. and Holmes, M. Description of an Early Intervention to Prevent Substance Abuse and Psychopathology in Recent Rape Victims. Behavior Modification, 29(1), pp. 1-33, 2005.

Infusion-LST Compared to LST as Usual

Findings from the first two years of a study to compare a standard Life Skills Training (LST) program with an infused (I-LST) approach was conducted in 9 small, rural school districts that were randomly assigned to LST, I-LST, or control conditions. Male and female subjects were in grade seven. The LST program significantly reduced alcohol use, binge drinking, marijuana use, and inhalant use after one year for females, and the I-LST program significantly reduced smoking, binge drinking, and marijuana use for females. At the end of the second year the I-LST program continued to impact female smoking, but all other results were non-significant. There were no effects on males at either time point. Smith, E.A. Evaluation of Life Skills Training and Infused-Life Skills Training in a Rural Setting: Outcomes at Two Years. Journal of Alcohol & Drug Education, 48(1), pp. 51-70, 2004.

Cost Comparison of LST and Infusion-LST

A cost-effectiveness comparison of the Life Skills Training (LST) to a LST curriculum infusion approach (I-LST) was conducted. Male and female seventh graders from nine rural schools (2 intervention conditions and control) were followed for two years. After one year, significant effects were observed only for females on alcohol, marijuana, and inhalant use in LST condition and for tobacco, alcohol, and marijuana use for I-LST females. After year two, only the I-LST program affected female smoking. Cost calculations for the two programs included expenditures for training and materials and estimates of teachers' salaries for the project period. Both programs were almost equally effective after one year, but LST was more cost-effective. I-LST cost more to implement, but sustained effects into year two and was therefore more cost-effective overall. Swisher, J. D. A Cost-Effectiveness Comparison of Two Approaches to Life Skills Training. Journal of Alcohol & Drug Education, 48(1) pp. 71-78, 2004.

Two Prevention Programs Reduce High Risk Behaviors Among African American Boys

This study was designed to test the efficacy of two programs to reduce high-risk behaviors, including drug use, delinquency, and high risk sexual behavior, among inner-city African-American youth. Students in grades 5 through 8 and their parents and teachers in twelve metropolitan Chicago schools were involved in a cluster randomized trial. The preventive interventions being tested were 1) a social development curriculum, focusing on social competence skills, and 2) a school/community intervention, consisting of the social development curriculum plus a school-wide climate and parent/community intervention. The control group received an attention-placebo. For boys, both programs significantly reduced violent behavior, provoking behavior, school delinquency, drug use, and recent sexual intercourse. The rate of condom use was increased among boys as well. The school/community intervention was significantly more effective than the curriculum-only intervention in reducing risk based on examination of a combined behavioral measure. There were no significant effects for girls. Flay, B.R., Gramlich, S., Segawa, E., Burns, J.L., and Holliday, M.Y. Effects of Two Prevention Programs on High Risk Behaviors among African American Youth. Archives of Pediatric and Adolescent Medicine, 158, pp. 377-384, 2004.

Research on Behavioral & Combined Treatments For Drug Abuse

Suicidal Behavior, Drug Use, and Depressive Symptoms

This 2-year prospective study of 470 patients following inpatient detoxification, examined factors associated with drug-related suicidal behavior using multivariable regression analyses. Suicidal behavior included suicidal ideation (SI) and suicide attempt (SA). Lifetime prevalence for SI was 28.5%, and for SA, 21.9%. During the 2-year follow-up, 19.9% of the sample endorsed suicidal ideation, and 6.9% reported a suicide attempt. Correlates of lifetime suicidal behavior included younger age, female, Hispanic, greater depressive symptoms, past sexual abuse, and problem sedative or alcohol use. Factors associated with suicidal behavior at follow-up included past suicidal behavior, more depressive symptoms, and more frequent benzodiazepine and alcohol abuse. These findings highlight the importance of addressing the recurrent suicide risk of patients with substance related disorder and frequent monitoring for changes in depressive symptoms and drug use. Wines, J.D., Saitz, R., Horton, N. J., Lloyd-Travaglini, C. and Samet, J. H. Drug and Alcohol Dependence, 76S, S21-S29, 2004.

Motivational Enhancement Therapy for Nicotine Dependence in Methadone-Maintained Pregnant Women

In this study, Dr. Haug and colleagues compared motivational enhancement therapy (MET) to standard-care practitioner advice for reducing smoking during pregnancy in a 2-group randomized design. Participants were 63 pregnant opioid-dependent smokers seeking substance abuse treatment, methadone maintenance, and prenatal care. At a 10-week follow-up, self-report and biological measures indicated no differences in smoking between the MET and standard-care groups. However, MET participants were more likely to have moved forward on the stage of change continuum than those in standard care. Intensive treatment for nicotine dependence, environmental interventions, and innovative harm reduction strategies are recommended to address the barriers to quitting observed in this population of pregnant women. Haug, N.A., Svikis, D.S. and Diclemente, C. Psychol Addict Behav. 18, pp. 289-292, 2004.

Correlates of Motivation to Quit Smoking in Methadone-Maintained Smokers Enrolled in a Smoking Cessation Trial

Investigators examined factors that may be associated with motivation to quit smoking in methadone-maintained persons. A sample of 255 smokers, enrolled in a smoking cessation research protocol, completed measures of their smoking motivation, smoking habit, quitting history, and intent to quit in the future. Analyses indicated that only number of cigarettes smoked per day and expectancies for success with smoking cessation were associated significantly with motivation to quit smoking. These results have implications for understanding motivational processes among methadone-maintained smokers and may help in the design of interventions that will assist this population with quitting smoking. Shadel, W.G., Stein, M.D., Anderson, B.J., Herman, D.S., Bishop, S., Lassor, J.A., Weinstock, M., Anthony, J.L. and Niaura, R. Addictive Behaviors, 20, pp. 295-300, 2005.

Research on Pharmacotherapies For Drug Abuse

Sex Influences Responses to Disulfiram Treatment in Cocaine-dependent Individuals

Sex and gender influences many physiological and behavioral responses to treatments. Investigators from Yale University and VA Connecticut Health Care System aimed to examine the differential response to disulfiram treatment of cocaine dependence by sex. Sex by treatment interactions from two pooled randomized clinical trials involving 191 cocaine-dependent subjects (36% female) were evaluated. Primary outcomes were days of abstinence and percentage of drug-free urine specimens. Men treated with disulfiram had better outcomes than those who were not. Women had an intermediate outcome regardless of whether they received disulfiram. Sex differences in response to disulfiram treatment may have important clinical and theoretical implications. Reasons for this apparent difference in sex-based response are not clear, but possible mechanisms worthy of greater study include differences in alcohol use by sex as well as differences in dopamine-mediated responses to cocaine and disulfiram. Nich, C., McCance-Katz, E.F., Petrakis, I.L., Cubells, J.F., Rounsaville, B.J. and Carroll, K.M. Sex Differences in Cocaine-dependent Individuals' Response to Disulfiram Treatment. Addictive Behaviors, 29(6), pp. 1123-1128, 2004.

Therapeutic Vaccines for Substance Dependence

Immunotherapies are under development as a new approach to the treatment of substance dependence. The drugs of abuse currently being tested using this new approach are nicotine, cocaine, phencyclidine and methamphetamine. In laboratory animal models, a range of immunotherapies, including vaccines, monoclonal antibodies and catalytic antibodies, have been shown to reduce drug seeking. In human clinical trials, cocaine and nicotine vaccines have been shown to induce antibody titers while producing few side effects. Studies in humans determining how these vaccines interact in combination with their target drug are underway. Overall, immunotherapy offers a range of potential treatment options: drug treatment, as well as the treatment of overdose, prevention of brain or cardiac toxicity and fetal protection in pregnant drug abusers. Haney, M. and Kosten, T.R. Therapeutic Vaccines for Substance Dependence. Expert. Rev. Vaccines. 3, pp. 11-18, 2004.

Research on Medical Consequences of Drug Abuse

The Efficacy of an Integrated Risk Reduction Intervention for HIV-positive Women with Child Sexual Abuse Histories

Child sexual abuse (CSA) is associated with HIV risk behaviors1 and more prevalent among women living with HIV than in the general population2. This randomized Stage II clinical trial tested the impact of a culturally congruent psychoeducational intervention designed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories. An ethnically diverse sample of 147 women were randomized to two conditions: an 11-session Enhanced Sexual Health Intervention (ESHI) or an attention control. Results based on "intent to treat" analyses of pre-post changes are reported in the article. Additional analyses explored whether the observed effects might depend on "intervention dose," i.e., number of sessions attended. Women in the ESHI condition reported greater sexual risk reduction than women in the control condition. Although there were no differences between women in the ESHI and control groups on medication adherence, women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at post-test than control women. The findings provide initial support for this culturally- and gender-congruent psychoeducational intervention for HIV-positive women with CSA, and highlight the importance of addressing the effects of CSA on sexual risk reduction and medication adherence in preventive interventions for women. Wyatt, G.E., Longshore, D., Chin, D., Carmona, J.V., Loeb, T.B., Myers, H.F., Warda, N., Liu, H., and Rivkin, I. The Efficacy of an Integrated Risk Reduction Intervention for HIV-positive Women with Child Sexual Abuse Histories. AIDS and Behavior, 8, pp. 453-462, 2004.

Gender Differences in Triazolam Pharmacokinetics

Sixty-one healthy men and women, aged 20 to 75 years, received single 0.25-mg doses of triazolam, a cytochrome P450 (CYP) 3A substrate benzodiazepine, and placebo in a double-blind crossover study. Among women, age had no significant effect on area under the triazolam plasma concentration curve (AUC) (Spearman r=0.14, P=.44) or clearance (r =-0.09, P=.62). Among men, AUC increased (r=0.43, P < .02) and clearance declined (r=-0.42, P <.02) with increasing age. Gender differences in triazolam kinetics were not apparent. Compared with placebo, triazolam impaired digit-symbol substitution test performance, increased observer-rated sedation, impaired delayed recall of information learned at 1.5 hours after dosing, and increased electroencephalographic beta amplitude. Among men, mean values of relative digit-symbol substitution test decrement (P <.002) and observer-rated sedation (P <.05) were significantly greater in elderly subjects compared with young subjects. Age-dependent differences among women reached significance for observer-rated sedation (P <.02). A combination of higher plasma levels and increased intrinsic sensitivity explained the greater pharmacodynamic effects of triazolam in elderly subjects. Although the findings are consistent with reduced clearance of triazolam in elderly men, individual variability was large and was not explained by identifiable demographic or environmental factors. Greenblatt, D.J., Harmatz, J.S., von Moltke, L.L., Wright, C.E. and Shader, R.I. Age and Gender Effects on the Pharmacokinetics and Pharmacodynamics of Triazolam, A Cytochrome P450 3A Substrate. Clin Pharmacol Ther., 76(5), pp. 467-479, 2004.

Effect of Hard-Drug Use on CD4 Cell Percentage, HIV RNA Level, and Progression to AIDS-Defining Class C Events Among HIV-Infected Women

In vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit ("hard")-drug use. Up to 3 periodic urine screens validated self-reported use. Outcomes were compared between hard-drug users (women using cocaine, heroin, methadone, or injecting drugs) and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use during pregnancy. In multivariate analyses, hard-drug use was not associated with change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause mortality (relative hazard = 1.10; 95% confidence interval, 0.61-1.98). Hard-drug users did, however, exhibit a higher risk of developing class C diagnoses (relative hazard = 1.65; 95% confidence interval, 1.00-2.72), especially herpes, pulmonary tuberculosis, and recurrent pneumonia. Hard-drug-using women may have a higher risk for nonfatal opportunistic infections. Thorpe, L.E., Frederick, M., Pitt, J., Cheng, I., Watts, D.H., Buschur, S., Green, K., Zorrilla, C., Landesman, S.H. and Hershow, R.C. Effect of Hard-Drug Use on CD4 Cell Percentage, HIV RNA Level, and Progression to AIDS-Defining Class C Events Among HIV-Infected Women. J Acquir Immune Defic Syndr. 37(3), pp. 1423-1430, 2004.

Drug Use and Disease Progression among HIV-Infected Women

Investigators from the Women and Infants HIV Transmission Study (WITS) have examined the relationship between drug use and four outcome measures: two markers of HIV disease progression (CD4 cell percentage, and HIV RNA level), and two clinical outcomes (progression to a first AIDS-defining class C event, and mortality. WITS is a multi-site longitudinal study of the health of HIV-infected mothers and their children, as well as mother-to-child HIV transmission. It is jointly supported by NIAID, NICHD, and NIDA. A woman was categorized as a Ôhard drug' user if she reported use of cocaine, crack, heroin, or other opiates (including methadone), if she reported engaging in injection drug use, or if her urine was positive for any of these drugs. Three time periods were examined for hard drug use (once during pregnancy, and two later points). Each woman was followed for up to five years. Outcomes were compared between hard drug users and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard drug use during pregnancy. In multivariate analyses, hard drug use was not associated with change in CD4 cell percentage, HIV RNA level, or all-cause mortality. Hard drug users did exhibit a higher risk of developing class C diagnoses, especially herpes, pulmonary tuberculosis, and recurrent pneumonia, leading to a conclusion that HIV-infected women who use hard drugs may be at higher risk for nonfatal opportunistic infections. The investigators consider a number of reasons why a relationship was not found between hard-drug use and CD4 cell percentage or HIV RNA level, given findings of relationships of cocaine and heroin to HIV replication and immune function in animal and in vitro studies, but they also point out that their findings are consistent with most prior epidemiologic evidence. Thorpe, L.E., Frederick, M., Pitt, J., et al. Effect of Hard-Drug Use on CD4 Cell Percentage, HIV RNA Level, and Progression to AIDS-Defining Class C Events among HIV-Infected Women. JAIDS, 37(3), pp. 1423-1430, 2004.

Adult Trauma and HIV Status among Latinas

Latinas have unique cultural factors that can contribute to their health. Recent immigration, documentation status, and language barriers can impact their lives in various ways. Additional stressors and experiencing traumatic events can impact psychological adjustment and substance use. This study tests the differential contribution of adult trauma and other life stressors to psychological adjustment and substance use among Latinas who differ in their HIV status and level of acculturation. A community sample of 121 (87 HIV-positive and 34 HIV-negative) 18 to 50 year old Latinas participated in this study using baseline and one-year follow-up data. Path analyses examined the influence of acculturation, HIV status, and adult trauma, including intimate partner violence (IPV) and sexual assault, on subsequent changes in psychological adjustment (depression) and substance use one year later. Demographic variables of age, education, and relationship status were controlled and further analyses examined the interactive influence of HIV status and acculturation and trauma on the outcomes. Findings indicate that both acculturation and HIV status were related to the outcome variables, but did not influence these over time, emphasizing the developmental stability of these processes. Education was the most prominent variable in protecting these women from HIV, depression, and intimate partner violence (IPV), but placed them at greater risk for illicit drug use. The primary predictors of change in the outcome variables were domestic and sexual trauma that were exacerbated by HIV positive status. Newcomb, M.D., and Carmona, J.V. Adult Trauma and HIV Status among Latinas: Effects Upon Psychological Adjustment and Substance Use. AIDS and Behavior, 8, pp. 417-428, 2004.

Services Research

Gender Differences in Older Adult Treatment Outcomes For Alcohol Dependence

This study examined clinical characteristics and treatment outcomes of older alcohol-dependent men and women in a mixed-age private outpatient chemical dependency program. The sample comprised 92 patients aged 55 to 77 (63 men and 29 women). The measures consisted of demographic characteristics, alcohol and drug use and dependence, drinking history, health status, psychiatric symptoms, length of stay in treatment, use of Alcoholics Anonymous and 6-month treatment outcomes. Results showed that women reported later initiation of heavy drinking (5+ drinks per occasion) than the men, but had similar drinking levels at the treatment intake interview. At the 6-month follow-up, 79.3% of women reported abstinence from alcohol and drugs in the prior 30 days versus 54.0% of men (p = .02). Greater length of stay in treatment predicted abstinence at 6 months. Among those who were not abstinent, none of the women reported heavy drinking in the 30 days prior to follow-up, whereas non-abstinent men reported a mean (SD) of 4.0 (9.2) heavy drinking days (p = .025). The results suggest that older women may have better drinking outcomes compared with older men, following treatment for alcohol dependence. Satre, D.D., Mertens, J.R., and Weisner, C. Gender Differences in Older Adult Treatment Outcomes for Alcohol Dependence. Journal of Studies on Alcohol, 65(5), pp. 638-642, 2004.

Five-Year Treatment Outcomes Favorable to Older Adults

This study compared 5-year treatment outcomes of older adults to those of middle-aged and younger adults in a large managed care chemical dependency program. Investigators examined age group differences in individual, treatment and extra-treatment factors, which may influence long-term outcome. Seventy-seven per cent of original study participants completed a telephone interview 5 years after outpatient chemical dependency treatment at Kaiser Permanente. This sample (N = 925) included 65 patients aged 55-77, 296 patients aged 40-54 and 564 patients aged 18-39 (age at baseline). Measures at follow-up included alcohol and drug use, Addiction Severity Index (ASI), Alcoholics Anonymous Affiliation Scale, social resource and self-reported health questions. Mortality data were obtained from contact with family members of patients as well as automated health plan records. Older adults were less likely to be drug-dependent at baseline than younger and middle-aged adults, and had longer retention in treatment than younger adults. At 5 years, older adults were less likely than younger adults to have close family or friends who encouraged alcohol or drug use. Fifty-two per cent of older adults reported total abstinence from alcohol and drugs in the previous 30 days versus 40% of younger adults. Older women had higher 30-day abstinence than older men or younger women. Among participants dependent only on alcohol, there were no significant age differences in 30-day abstinence. In logistic regression analysis, age group was not significant. Variables associated with greater age that independently predicted 30-day abstinence in the logistic regression model included longer retention in treatment and having no close family or friends who encouraged alcohol or drug use at 5 years; female gender was also significant. Results indicate that older adults have favorable long-term outcome following treatment relative to younger adults, but these differences may be accounted for by variables associated with age such as type of substance dependence, treatment retention, social networks and gender. Age differences in these characteristics inform intervention strategies to support long-term recovery of older adults and provide direction for investigation of how age affects outcome. Satre, D.D., Mertens, J.R., Arean, P.A and Weisner, C. Five-year Alcohol and Drug Treatment Outcomes of Older Adults Versus Middle-aged and Younger Adults in a Managed Care Program. Addiction, 99(10), pp. 1286-1297, 2004.

An HIV Prevalence-based Model for Estimating Urban Risk Populations of Injection Drug Users and Men Who Have Sex with Men

Issues of cost and complexity have limited the study of the population sizes of men who have sex with men (MSM) and injection drug users (IDUs), two groups at clearly increased risk for human immunodeficiency virus (HIV) and other acute and chronic diseases. Authors developed a prototypical, easily applied estimation model for these populations and applied it to Miami, Florida. This model combined HIV prevalence estimates, HIV seroprevalence rates, and census data to make plausible estimates of the number and proportion of MSM and IDUs under a number of assumptions. Sensitivity analyses were conducted to test the robustness of the model. The model suggests that approximately 9.5% (plausible range 7.7%-11.3%) of Miami males aged 18 years or older are MSM (point estimate, N =_76,500), and 1.4% (plausible range 0.9%-1.9%) of the total population aged 18 years or older are IDUs (point estimate, N=_23,700). Males may be about 2.5 times more likely than females to be IDUs. The estimates were reasonably robust to biases. The model was used to develop MSM and IDU population estimates in selected urban areas across Florida and should be replicable in other medium-to-large urban areas. Such estimates could be useful for behavioral surveillance and resource allocation, including enhanced targeting of community-based interventions for primary and secondary HIV prevention. Lieb, S., Friedman, S.R., Zeni, M.B., Chitwood, D.D., Liberti, T.M., Gates, G.J., Metsch, L.R., Maddox, L.M., and Kuper, T. Comprehensive Model of Substance Abuse Treatment Processes Introduced. Journal of Urban Health: Bulletin of the New York Academy of Medicine, 81(3), pp. 401-415, 2004.

Mixed Results for Step Down Continuing Care in the Treatment of Substance Abuse

This study examined the predictors of participation in step down continuing care (i.e., contiguous episode of care at a lower level of intensity) in publicly funded substance abuse treatment programs, and the relation between participation in step down care and alcohol and crack cocaine use outcomes over a 36-month follow-up. The sample included patients in residential/inpatient programs (IP; N = 134) and intensive outpatient programs (IOP; AT = 370). About one-third of IP patients received step down continuing care; fewer than 25% of IOP patients received step down continuing care. Patients who received step down continuing care following IP had greater social support at intake and were more likely to be female and White than those who did not receive continuing care. Patients who received continuing care following IOP were more likely than those who did not to be female and employed, and were older, had higher self-efficacy, and shorter lengths of stay in IOP. Participation in step down care was not associated with other factors assessed at intake. In the IP sample, receiving step down continuing care was not associated with better alcohol or crack cocaine use outcomes over the 36-month follow-up. In the IOP sample, there were no main effects favoring continuing care for either alcohol or crack cocaine use outcomes. However, patients who received continuing care had less crack cocaine use in the first six months of the follow-up. These findings suggest that new models of continuing care are needed that are more acceptable to patients, produce better outcomes, and are cost-effective. McKay, J.R., Foltz, C., Leahy, P., Stephens, R., Orwin, R.G., and Crowley, E.M. Step Down Continuing Care in the Treatment of Substance Abuse: Correlates of Participation and Outcome Effects. Evaluation and Program Planning, 27(3), pp. 321-331, 2004.

To What Extent Are Key Services Offered in Treatment Programs for Special Populations?

Many substance abuse treatment (SAT) facilities offer programs tailored for special populations such as women, adolescents, gays/lesbians and others. Previous research shows that there are specific services that are integral to the successful treatment of these populations (e.g., family therapy for adolescents, childcare and transportation assistance for women, and HIV testing and counseling for gays/lesbians). This study examines whether facilities that report having programs for special populations actually offer the recommended services. The data come from the 2000 National Survey of Substance Abuse Treatment Services, which contains information on service offerings, special programs and other characteristics for all SAT facilities in the USA. The results indicate that facilities with special programs are more likely to offer the recommended key services. However, often less than half of these facilities provide the key services. There are consistent differences by ownership status, with for-profit facilities less likely to offer many of the key services. To What Extent are Key Services Offered in Treatment Programs for Special Populations? Olmstead, T. and Sindelar, J.L. Journal of Substance Abuse Treatment, 27(1), pp. 9-15, 2004.

Intramural Research

Molecular Neuropsychiatry Section, Molecular Neuropsychiatry Research Branch

Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutics Research Branch

Neonatal Abstinence Syndrome in Methadone-exposed Infants is Altered by Level of Prenatal Tobacco Exposure

Maternal tobacco consumption during pregnancy has been associated with lower birth weight infants, preterm births, intrauterine growth retardation, smaller head circumference and increase in morbidity, yet few studies have examined the role tobacco has on the opiate neonatal abstinence syndrome (NAS). This study examined the effect of prenatal tobacco exposure on NAS for infants born to mothers maintained on methadone during gestation. Twenty-nine pregnant women and their newborn infants participated in this study. Tobacco exposure was based on maternal self-report with 16 women reporting cigarette consumption of 10 or less per day and 13 reporting smoking 20 cigarettes or more a day. The onset, peak, and duration of NAS were examined. Results showed that infants born to mothers who reported smoking 20 or more cigarettes per day had significantly higher NAS peak scores of 9.8 versus 4.8, and took longer to peak (113.0 h versus 37.8 h), than light smokers of 10 or fewer cigarettes per day. Investigators concluded that tobacco use in conjunction with methadone plays an important role in the timing and severity of NAS in prenatally exposed infants. Choo, R.E., Huestis, M.A., Schroeder, J.R., Shin, A.S. and Jones, H.E. Drug and Alcohol Dependence, 75, pp. 253-260, 2004.

Methamphetamine and Amphetamine Concentrations in Meconium of Neonates of Women Enrolled in the IDEAL Study of In Utero Methamphetamine Exposure

The Infant Development, Environment, and Lifestyle (IDEAL) study is a multi-center, longitudinal investigation of the effects of prenatal methamphetamine exposure. Meconium, a useful matrix for identifying in utero drug exposure, was employed to identify gestational drug use. Of the 13,808 mothers screened, 1631 were consented and 176 enrolled. MA exposed mothers (n=84) were identified by self-report of gestational MA use and/or GC/MS confirmation of MA, AMP, and/or MDMA in infant meconium. Comparison participants (n=92) were matched by race, birth weight, maternal education and type of insurance, denied amphetamines use and had negative meconium results. Among the 1631 mothers, self-reported use rates were 5.2% (amphetamines), 25% (tobacco) and 5.9% (cannabis). Positive meconium screening rates were 3.6% for any amphetamine, 20% cotinine and 11.2% cannabis. For specimens that screened positive, 40.7% of amphetamines and 20.2% of cannabis specimens were confirmed. On average, 68% of the meconium from neonates whose mothers reported 3rd trimester use had detectable MA, while detection rates were ²10% for self-reported use during the 1st and/or 2nd trimesters. Mean ± SD, median and range of MA concentrations were 3674 ± 3406, 2623, 479 to 13,431 ng/g meconium and AMP 569 ± 543, 403, 30 to 2000 ng/g meconium in infants whose mothers reported 3rd trimester use. However, the highest MA (19,376 and 16,976 ng/g) and AMP (2765 ng/g) concentrations were found in offspring born to women who reported MA use only in the 1st or 1st and 2nd trimesters, raising questions about the self-report. The log transformed meconium MA concentrations significantly correlated with the frequency of MA use in the 3rd trimester (r=0.645, P=0.004), although variability prevents prediction of frequency of use for an individual mother. AMP was always detected in MA positive meconium. In 55% of the GCMS positive samples, the ratios of amphetamine to MA were 0.1 to 0.2; 14% were less than 0.1 and 18% were 0.2 to 0.3. Meconium analysis for MA is a useful adjunct to self-report for identification of MA exposure; however, the greatest sensitivity was achieved with specimens collected from offspring of women who reported use in the 3rd trimester. Further research is needed to determine if there are additional MA metabolites in meconium that could improve the identification of MA-exposed infants. Zhao, Z., Liu, J., LaGasse, L.L., Derauf, C., Grant, P., Shah, R., Arria, A., Haning, W., Smith, L.M., Lester, B. and Huestis, M.A., Poster, 2004. Joint Meeting of the Society of Forensic Toxicologists and The International Association of Forensic Toxicologists, Washington, DC, August 28-September 3, 2004.