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Director's Report to the National Advisory Council on Drug Abuse - September, 2005

Research Findings - Behavioral and Brain Development Research

Quantitative Analysis of Diffusion Tensor Orientation: Theoretical Framework

Dr. Andrew Alexander and colleagues of the University of Wisconsin-Madison have developed a series of visual and quantitative tools for representing the coherence and directional organization of white matter tracts in the human brain. These authors have also shown that the methods developed are sensitive to changes in the structural organization caused by infiltrative disease. Wu, Y-C., Field, A.S., Chung, M.K., Badie, B. and Alexander, A.L., Magnetic Resonance in Medicine. 52, pp. 1146-1155, 2004.

Marijuana Impairs Growth Mid-gestation Fetuses

Dr. Yasmin Hurd and her colleagues analyzed the growth rate in fetuses that had been exposed to marijuana in utero and compared their growth with non-exposed fetuses. In a sample of 44 exposed and 95 non-exposed fetuses analyzed at gestational ages of from 17 to 22 weeks it was found that the exposed fetuses had significantly reduced body weight and foot length, even when the data were adjusted to account for maternal alcohol consumption and smoking (tow other factors that can impair fetal development). These findings provide evidence of a negative impact of marijuana on intrauterine growth in human fetuses. Hurd, Y.L., Wang, X., Anderson, V., Beck, O., Minkoff, H., and Dow-Edwards, D. Neurotoxicology and Teratology. 27(2), pp. 221-229, 2005.

fMRI Response to Spatial Working Memory in Adolescents with Comorbid Marijuana and Alcohol Use Disorders

Dr. Susan Tapert and her colleagues compared the brain activation patterns of 15 adolescents that had used both marijuana and alcohol (MAUD participants) with those of 15 adolescents that had used only alcohol (AUD) and 19 adolescents that had used neither while performing a spatial working memory task. The results showed that, even though the 3 groups of adolescents had similar performance on the task, MAUD adolescents showed less activation in the inferior frontal and temporal regions than the AUD and the control groups, and more activation in dorsolateral prefrontal regions and deactivation in the anterior cingulate cortex than the control group. These findings suggest that marijuana use in adolescents may cause deficits in attentional mechanisms and evoke compensatory responses in areas that subserve spatial working memory. Schweinsburg, A.D., Schwiensburg, B.C., Cheung, E.H., Brown, G.G., Brown, S.A. and Tapert, S.F. Drug and Alcohol Dependence. 79, pp. 201-210, 2005.

Heritability of Substance Dependence in a Native American Population

This study estimated the heritability of substance dependence and associated symptoms in a sample of Southwest California (Mission) Indians. Dependence diagnoses for alcohol, marijuana, stimulants and a measure of regular tobacco usage, any drug dependence or tobacco usage were obtained. Heritability estimates were calculated using variance component methods, as implemented in SOLAR. In this population, marijuana dependence (0.38) and regular tobacco use (0.43), alcohol dependence (0.29), and stimulant dependence (0.25) showed evidence for moderate genetic influences as determined by heritability estimates. The authors conclude that marijuana dependence, regular tobacco usage and composite phenotypes constructed from alcohol dependence symptoms for antisocial problems, drinking severity and withdrawal generally have patterns of familial aggregation, suggesting that they can be successfully used for linkage analysis in this Southwest California Indian sample. Wilhelmsen, K.C. and Ehlers, C. Heritability of Substance Dependence in a Native American Population. Psychiatric Genetics, 15(2), pp. 101-107, 2005.

Patterns of Polydrug Use among Ketamine Injectors in New York City

Polydrug use is an important public health issue since it has been linked to significant adverse health outcomes. Recently, club drugs, including ketamine and other drugs used in dance/rave scenes, have been identified as key substances in new types of polydrug using patterns. While seemingly a self-explanatory concept, "polydrug" use constitutes multiple drug using practices that may impact upon health risks. Ketamine, a club drug commonly administered intranasally among youth for its disassociative properties, has emerged as a drug increasingly prevalent among a new hidden population of injection drug users (IDUs). Using an ethno-epidemiological methodology, the researchers interviewed 40 young (< 25 years old) ketamine injectors in New York during 2000-2002 to describe the potential health risks associated with ketamine and polydrug use. Findings indicate that ketamine was typically injected or sniffed in the context of a polydrug using event. Marijuana, alcohol, PCP, and speed were among the most commonly used drugs during recent ketamine using events. Polydrug using events were often quite variable regarding the sequencing of drug use, the drug combinations consumed, the forms of the drug utilized, and the modes of administrating the drug combinations. The investigators suggest that future research should be directed towards developing a more comprehensive description of the risks associated with combining ketamine with other drugs, such as drug overdoses, the transmission of bloodborne pathogens such as HIV and HCV, the short- and long-term effects of drug combinations on cognitive functioning, and other unanticipated consequences associated with polydrug use. Lankenau, S.E. and Clatts, M.C. Patterns of Polydrug Use among Ketamine Injectors in New York City. Substance Use and Misuse, 40, pp. 1381-1397, 2005.

Neurocognitive Consequences of Marijuana in Young Adults for Whom Pre-Drug Use Performance is Known

This report examined effects of current and past regular use of marijuana among young adults for whom pre-drug use performance had been ascertained in a prospective, longitudinal study. A total of 113 young adults (17-21 years of age), assessed since infancy, were evaluated using neurocognitive tests for which commensurate measures were obtained prior to the initiation of marijuana smoking (i.e., 9-12 years of age). Marijuana users, determined by urinalysis and self-report, were categorized as light (<5 joints per week) and heavy (5 joints per week) current users and former users, the latter having used the drug regularly in the past (1 joint per week) but not for at least 3 months. A third of the participants were using marijuana on a regular basis at the time of assessment, with half being heavy users. Among former, regular users, approximately half had been smoking 5 or more joints per week. Overall IQ, memory, processing speed, vocabulary, attention, and abstract reasoning were assessed. After accounting for potentially confounding factors and pre-drug performance in the appropriate cognitive domain, current regular heavy users did significantly worse than non-users in overall IQ, processing speed, and in immediate and delayed memory. In contrast, the former marijuana smokers did not show any cognitive impairments. The authors conclude that residual marijuana effects are evident beyond the acute intoxication period in current heavy users after taking into account pre-drug performance, but similar deficits are no longer apparent 3 months after cessation of regular use, even among former heavy using young adults. The investigators suggest caution in interpreting and generalizing the results, pointing out that the average length of time of regular use was relatively short (i.e., slightly over 2 _ years). They also note that the literature is inconclusive regarding associations between lifetime duration of former use and cognitive functioning. Fried, P.A., Watkinson, B., and Gray, R. Neurocognitive Consequences of Marijuana - A Comparison with Pre-Drug Performance. Neurotoxicology and Teratology, 27, pp. 231-239, 2005.

Prenatal Tobacco Exposure and Offspring Smoking in Early Adolescence

In this prospective study of a birth cohort of 567 14-year-olds, investigators at the University of Pittsburgh examined relationships among trimester-specific prenatal tobacco exposure (PTE), offspring smoking, and other correlates of adolescent smoking. Average age of the adolescents was 14.8 years (range: 13.9-16.6 years). Approximately half of the sample was female, and about half was African-American. Data on maternal tobacco and other substance use were collected both prenatally and postnatally. Fifty-one percent of the mothers were prenatal smokers and 53% smoked when their children were 14 years old. PTE in the third trimester significantly predicted offspring smoking (ever/never, smoking level, age of onset) when demographic and other prenatal substances were included in the analyses. PTE remained a significant predictor of the level of adolescent smoking when maternal and child psychological characteristics were added to the model. When more proximal measures of the child's smoking were included in the model, including mother's current smoking and friends' smoking, PTE was no longer significant. Significant predictors of adolescent smoking at age 14 were female gender, Caucasian race, child externalizing behavior, maternal anxiety, and child depressive symptoms. The authors conclude that although direct effects of PTE on offspring smoking behavior have previously been reported from this study and by others, by early-adolescence, this association was not significant in this sample after controlling for the more proximal covariates of adolescent smoking such as mother's current smoking and peer smoking. They also note that many of the reports in the literature that indicate a relationship between PTE and offspring smoking have been retrospective or have not included important variables such as other prenatal substance exposures, maternal and child psycho-social characteristics, mother's current smoking, and friends' smoking. Cornelius, M.D., Leech, S.L., Goldschmidt, L. and Day, N.L. Is Prenatal Tobacco Exposure a Risk Factor for Early Adolescent Smoking? Neurotoxicology and Teratology, 27, pp. 667-676, 2005.

School Performance of Children with Gestational Cocaine Exposure

Researchers from the University of Pennsylvania have reported results on school performance in a sample of children exposed to cocaine in utero. At the completion of fourth grade, a total of 135 children (62 with gestational cocaine exposure and 73 without) who were enrolled at birth and followed prospectively, were evaluated using report card data, standardized test results, teacher and parent report, and natal and early childhood data. Successful grade progression was defined as completing grades 1 through 4 without being retained. Cocaine-exposed and control children were similar in school performance (all p0.10): successful grade progression (71% cocaine-exposed vs. 84% control), Grade Point Average (2.40.8 vs. 2.60.7), reading below grade level (30% vs. 28%), and standardized test scores below average (reading [32% vs. 35%], math [57% vs. 44%], science [39% vs. 36%]). Children with successful progression, regardless of cocaine exposure, had higher Full Scale IQ and better home environments. The researchers conclude that in this inner-city cohort, cocaine-exposed and control children had similar poor school performance, with better home environment and higher Intelligence Quotient associated with an advantage for successful grade progression, regardless of gestational cocaine exposure. Hurt, H., Brodsky, N.L., Roth, H., et al. School Performance of Children with Gestational Cocaine Exposure. Neurotoxicology and Teratology, 27, pp. 23-211, 2005.

Prenatal Drug Exposure and Selective Attention in Preschoolers

Based on research conducted at Case Western Reserve University, a recent report focused on selective attention in a large, polysubstance cocaine-exposed cohort of 4-year-olds and their at-risk comparison group. Maternal pregnancy use of cocaine and use of cigarettes were both associated with increased commission errors, interpreted as indicative of inferior selective attention. Severity of maternal use of marijuana during pregnancy was positively correlated with omission errors, suggesting impaired sustained attention. Substance exposure effects were independent of maternal postpartum psychological distress, birth mother cognitive functioning, current caregiver functioning, other substance exposures, and child concurrent verbal IQ. Noland, J.S., Singer, L.T., Short, E.J., et al. Prenatal Drug Exposure and Selective Attention in Preschoolers. Neurotoxicology and Teratology, 27, pp. 429-438, 2005.

Relative Ability of Biologic Specimens and Interviews to Detect Prenatal Cocaine

Exposure University of Florida researchers recruited women in a labor and delivery service, enrolling all consenting patients with a history of prenatal cocaine use and the next admission with no recorded use. During the immediate postpartum period, private, structured interviews were carried out to obtain details of prenatal cocaine use and to identify a priori exclusion criteria (other illicit drug use, high alcohol use and chronic illnesses and medications). Amniotic fluid, cord blood, infant urine, meconium, and maternal hair were also collected. All specimens were blindly analyzed with respect to exposure, using gas chromatography/mass spectrometry. Of 115 subjects, 46 had one or more biologic specimens positive for cocaine metabolites and five admitted prenatal use, but had negative specimens. Of these 51 identified as users by any method, 38 admitted, 32 were positive for urine, 28 for hair, and 25 for meconium. Of the 38 admitters, 87% had positive specimens. Of the 77 denying use, 17% were positive. Urine was most frequently positive in identified users, 67% overall and 62% of users who denied. Hair was next, positive in 65% of all users and 50% of users who denied. Of the 13 subjects who denied use but were positive on at least one specimen, four were identified solely by urine, two only by hair and one only by meconium. Self-report identified five users with all negative specimens. The authors conclude that although no one method identified all users, the single method that maximally identified users was detailed history taken by experienced interviewers. Eyler, F.D., Behnke, M., Wobie, K., Garvan, C.W. and Tebbett, I. Relative Ability of Biologic Specimens and Interviews to Detect Prenatal Cocaine Use. Neurotoxicology and Teratology, 27, pp. 677-687, 2005.


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