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Director's Report to the National Advisory Council on Drug Abuse - February, 2004

Research Findings - Research on AIDS and Other Medical Consequences of Drug Abuse - Non-AIDS Research

Prenatal Drug Exposure and Auditory Brain Response in Infancy

Results from the multi-site Maternal Lifestyle Study (MLS) indicate that prenatal cocaine and/or opiate exposure affects neural transmission in one-month old infants. Auditory brain stem response (ABR) was measured as an indicator of the functional integrity of the central nervous system in 477 exposed and 554 comparison infants matched for race, sex, and gestational age. Study sites were located in Detroit, Memphis, Miami, and Providence. Analyses were conducted for exposed and comparison groups and for level of prenatal cocaine exposure, with adjustment for covariates (alcohol, marijuana, tobacco, gestational age at birth, social class, and site). Heavy prenatal cocaine exposure (3 days per week, first trimester) was associated with an increase in the I-III, I-V, and III-V interpeak latencies, indicating prolongation of neural transmission. The I-V interpeak latency represents central brain stem conduction time from acoustic nerve to inferior colliculus in the midbrain, and may reflect delayed brainstem maturation. Heavy cocaine exposure was also related to a shorter latency to peak I, possibly indicating hypersensitivity to auditory stimuli. Hypersensitivity, or excitability, has been reported previously for cocaine-exposed infants. Infants with prenatal opiate exposure showed a longer latency to Peak V and a longer III-V interpeak latency, supporting previous findings in small samples of opiate-exposed infants. Lester, B.M., LaGasse, L., Seifer, R., et al. The Maternal Lifestyle Study (MLS): Effects of Prenatal Cocaine and/or Opiate Exposure on Auditory Brain Response at One Month. J Pediatrics, 142, pp. 279-285, 2003.

Cumulative Risk and Parenting Stress for Mothers of Drug-Exposed Infants

This study examined the relationship between cumulative environmental risks, parenting attitudes (parenting stress and potential for child abuse and neglect), and child development in a subgroup of 161 mothers and their drug-exposed infants who were part of a randomized longitudinal study of a home-based early intervention. Mothers with five or more environmental risk factors reported higher parenting stress than women with four or fewer risks and greater potential for child abuse and neglect than women with two or fewer risks at 6 and 18-month visits. Risks included depression, domestic violence, non-domestic violence, family size, homelessness, incarceration, absence of significant other in home, negative life events, psychiatric symptoms, and severity of drug use. Amount of risk was not related to children's mental, motor, or language development at 6, 12, or 18 months of age. Nair, P., Schuler, M.E., Black, M.M., Kettinger, L., and Harrington, D. Cumulative Environmental Risk in Substance Abusing Women: Early Intervention, Parenting Stress, Child Abuse Potential and Child Development. Child Abuse and Neglect, 27, pp. 997-1017, 2003.

Drug-Exposed Infants, Early Home Intervention, and Developmental Outcomes

Researchers at the University of Maryland have reported on effects of a home intervention program for prenatally drug-exposed infants and their families. Biological mother-infant dyads were randomly assigned to a control (n=54) or intervention (n=54) group at 2 weeks postpartum. Control families received brief monthly tracking visits. Intervention families received a developmentally-oriented home intervention, weekly through 6 months, and bi-weekly from 6 to 18 months. Developmental assessments were carried out at 6, 12, and 18 months of age, as were assessments of ongoing maternal drug use. During the 18-month period under study, there were no significant group differences in entry into drug treatment, or in reported ongoing use of cocaine and/or heroin, alcohol, or marijuana. Ongoing cocaine and/or heroin use was associated with lower infant mental development scores, and infant mental scores declined over the first 18 months post partum in this inner-city, low socioeconomic status sample. Nonetheless, infants in the intervention group had higher mental and motor development scores than did control infants. The investigators note the importance of including a drug treatment component in future interventions. Schuler, M.E., Nair, P. and Kettinger, L. Drug-Exposed Infants and Developmental Outcome. Archives of Pediatric and Adolescent Medicine, 157, pp. 133-138, 2003.

Amantadine Does Not Modulate Reinforcing, Subjective, or Cardiovascular Effects of Cocaine in Humans

Data from several clinical studies have suggested that amantadine, which has dopaminergic agonist and glutamatergic antagonist effects, may be useful for the treatment of cocaine dependence. The interaction between amantadine and smoked cocaine was examined in 10 cocaine smokers (7 men, 3 women), who participated in a 26-day inpatient study. Participants were maintained on amantadine (0 and 100 mg bid) for 5 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked a sample dose of cocaine base (0, 12, 25, and 50 mg) once, and were subsequently given five choice opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose varied systematically. Cocaine produced stimulant-like reinforcing, subjective, and physiological effects. Amantadine maintenance did not modify the choice to self-administer smoked cocaine. The investigators stated that these findings, taken together with the decidedly mixed literature, suggest that amantadine (100 mg bid) will not have a role in the treatment of cocaine dependence. Collins, E.D., Vosburg, S.K., Hart, C.L., Haney, M. and Foltin, R.W. Amantadine Does Not Modulate Reinforcing, Subjective, or Cardiovascular Effects of Cocaine in Humans. Pharmacol Biochem Behav., 76(3-4), pp. 401-407, 2003.

Chronic Drug Use and Reproductive Health Care among Low Income Women in Miami, Florida: A Comparative Study of Access, Need and Utilization

Interviews of low-income women in Miami, FL, addressed reproductive health issues in a stratified, network-referred sample of chronic drug users (CDUs) and socially and ethnically similar women who were not CDUs. Women who were not CDUs were significantly more likely to report a regular source of health care than CDUs. About one third of each group reported experiencing reproductive health problems (other than pregnancy) in the 12 months preceding their interview. Chronic drug users were twice as likely to report that these problems remained untreated. Measures of use of preventive services (physical exam, breast exam, pelvic exam, family planning visit) consistently showed lower use by CDUs. A higher proportion of women who were not CDUs reported pregnancies in the 12 months preceding interview. The 32 pregnant CDUs were much less likely to have received prenatal care than the 42 pregnant women who were not CDUs. For women who reported a pregnancy in the year preceding interview, logistic regression analysis showed a strong and robust negative effect of being a CDU on receiving prenatal care even when the effects of having a usual source of care and having third-party coverage were controlled. Crandall, L.A., Metsch, L.R., McCoy, C.B., Chitwood, D.D. and Tobias, H. Chronic Drug Use and Reproductive Health Care among Low Income Women in Miami, Florida: A Comparative Study of Access, Need and Utilization. J Behav Health Serv and Res., 30(3), pp. 321-331, 2003.

Relapse in Outpatient Treatment for Marijuana Dependence

The current study provides an initial examination of lapse and relapse to marijuana use among 82 individuals who achieved at least 2 weeks of abstinence during outpatient treatment for marijuana dependence. Seventy-one percent used marijuana at least once (i.e., lapsed) within 6 months of initial abstinence, averaging 73 days (SD = 50) till lapsing. Similarly, 71% of those who lapsed, relapsed to heavier use defined as at least 4 days of marijuana use in any 7-day period. Early lapses were more strongly associated with consequent relapse. Previous studies have noted that marijuana-dependent outpatients experience difficulty initiating abstinence from marijuana much as do those dependent on other substances. The present data suggest that these similarities extend to difficulty maintaining abstinence. Moore, B.A. and Budney, A.J. Relapse in Outpatient Treatment for Marijuana Dependence. J Subst Abuse Treat., 25(2), pp. 85-89, 2003.

The Time Course and Significance of Cannabis Withdrawal

Researchers at Vermont University report that withdrawal symptoms following cannabis cessation are comparable to tobacco and other withdrawal syndromes. Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset occurred between days 1-3, peak effects between days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. DSM criteria for "cannabis withdrawal" are proposed. Budney, A.J., Moore, B.A., Vandrey, R.G., Hughes, J.R., et al. The Time Course and Significance of Cannabis Withdrawal. J Abnormal Psych., 112(3), pp. 393-402, 2003.

Treatment of Marijuana Dependence: A Review of the Literature

Until recently, relatively little research has focused on the treatment of marijuana abuse or dependence; however, marijuana use disorders are now receiving increased attention. This paper reviews the initial clinical trials evaluating the efficacy of outpatient treatments for adult marijuana dependence. Findings from five controlled trials of psychotherapeutic interventions suggest that this disorder appears responsive to the same types of treatment as other substance dependencies. Moreover, these initial studies suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Strengths and weaknesses of the data are presented. Preliminary data from less controlled studies relevant to the treatment of marijuana dependence are discussed to suggest future research areas. Although very few studies on treatment for marijuana abuse and dependence have been completed, the initial reports identify promising treatment approaches and demonstrate a need for more research on the development of effective interventions. McRae, A., Budney, A. and Brady, K. Treatment of Marijuana Dependence: A Review of the Literature. J Subst Abuse Treat., 24(4), pp. 369-376, 2003.


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