Drug Abuse Prevention

Research Findings from February, 2002 Director's Report

This section lists selected summaries from NIDA funded research projects that investigate youth drug abuse prevention. The summaries provided were selected from recent issues of the Director's Report to the National Advisory Council on Drug Abuse. For a more comprehensive listing of NIDA funded projects see the Director's Report.

Rats Exposed to Methylphenidate during Development Respond Differently to Cocaine as Adults

Previous research had suggested that children with attention-deficit hyperactivity disorder who are treated with Ritalin (methylphenidate) are less likely to become substance abusers later in life than similar children who do not receive such treatment (Biederman et al, 1999). NIDA-supported researchers in Boston recently reported that the administration of methylphenidate to pre-adolescent rats results in behavioral and molecular adaptations that persist into adulthood and that the same treatment in adult rats results in different patterns of behavior and molecular adaptations. Rats were given a clinically relevant dose of methylphenidate or vehicle daily from postnatal days 20-35 or from days 50-65 and were studied 25 days later. Cocaine reward was assessed using a conditioned place preference procedure at a low and a high dose of cocaine. Rats treated in the earlier developmental period with vehicle showed the expected preference for cocaine in this test whereas those treated with the methylphenidate failed to establish a place preference to cocaine, suggesting that cocaine was less rewarding or aversive in these animals. Animals treated and tested as adults consistently demonstrated a preference for cocaine. Numerous neuroadaptations have been described in adult rats after treatment with cocaine, including increases in CREB (cAMP response element binding protein) and changes in NMDA receptors (GluR1, GluR2, NMDAR1). When the brains of the animals treated as juveniles were examined, CREB had increased as much as in animals treated as adults. However, there was no corresponding increase in GluR2, as there was in the animals treated as adults. These results show that neurobiological adaptations persist after treatment with methylphenidate and that the adaptive responses are different, depending on the age at which treatment occurred. Furthermore, they may represent neurobiological substrates that mediate the rewarding and aversive properties of stimulants. These findings suggest that the neurobiological impact of methylphenidate depends critically on the developmental stage during which it is administered. Andersen, S.L., Aravanitogiannis, A., Pliakas, A.M., LeBlanc, C. and Carlezon, Jr., W.A., Altered Responsiveness to Cocaine in Rats Exposed to Methylphenidate during Development. Nature Neuroscience, 5, pp. 13-14, 2002.

Methylphenidate Treatment of Adolescent Rats Enhances Behavioral Reactivity and Vulnerability to Self-Administer Cocaine as Adults

The recent dramatic increase in the use of methylphenidate (MP; Ritalin‘) to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents has raised the question of whether long-term exposure to this psychostimulant might lead to increased vulnerability for drug abuse disorders. Epidemiological studies have yielded conflicting answers to this important question, and previous studies in animal models have also been inconclusive, in part because of controversy about whether the MP dosages tested in rats have replicated therapeutic levels in humans. In a recent study, Dr. Cindy Brandon, a NIDA NRSA postdoctoral fellow in Dr. Frank White’s laboratory, developed an animal model to assess whether repeated exposure to MP during adolescence enhances locomotor stimulant effects of cocaine and increases vulnerability to self administer this drug in adulthood. Adolescent rats (5-weeks old – age equivalent to the beginning of adolescence) received seven daily injections of moderate doses (10 mg/kg or 5 mg/kg) of MP and were then tested as adults (8-weeks old) for their response to a single dose of cocaine. The pre-exposure to MP significantly increased sensitivity to the locomotor activating effects of the cocaine, a phenomenon known as cross sensitization. In a separate experiment intended to emulate more closely dosing regimens in humans and associated plasma drug concentrations, the investigators pretreated adolescent rats with a low dose of MP (2 mg/kg) and challenged them with various doses of cocaine. The rats showed no cross sensitization at any of the cocaine doses, but when they were tested in a self-administration (SA) protocol, they acquired SA at the low cocaine dose of 75 mg/kg and showed enhanced intake of cocaine compared to control animals pretreated with saline. Thus, animals exposed to the low dose of MP during adolescence appeared considerably more vulnerable to the reinforcing effects of cocaine as adults even though they did not show locomotor cross sensitization. The results of this study suggest that known neuroadaptations produced by therapeutic treatment with MP, such as decreased dopamine transporter binding, may increase drug abuse vulnerability. Brandon, C.L., Marinelli, M., Baker, L.K. and White, F.J. Enhanced Reactivity and Vulnerability to Cocaine following Methylphenidate Treatment in Adolescent Rats. Neuropsychopharmacology, 25, pp. 651-661, 2001.

Repeated Maternal Separation in Neonatal Rats Alters Sensitivity to Chronic Morphine in a Sex-Dependent Manner

Research has shown that neonatal rat pups separated from their mothers for several hours each day, during the first few weeks of life, subsequently exhibit elevated stress-reactivity during adulthood. Exaggerated responsivity is evident from both behavioral and physiological indices. Moreover, animals exposed to early separation distress with this paradigm are also more sensitive to the locomotor activating effects of acute psychostimulant drugs and are more vulnerable to acquire psychostimulant self-administration. Dr. Steve Holtzman and his colleagues at Emory University School of Medicine have been examining the behavioral and physiological effects of opiates in animals exposed to the early separation procedure, and using this paradigm to uncover influences of early post-natal stress on neuroadaptations to chronic drug administration. These investigators report that 3 hours of separation from the dam, in comparison to handled and nonhandled controls, alters subsequent sensitivity to morphine’s antinociceptive effects. Notably, after this extended period of early separation, male but not female offspring were less sensitive to the antinociceptive effects of morphine. Also, the development of tolerance to antinociceptive effects was enhanced in males exposed to early maternal separation, but not in females. In both male and female rats, daily 3 hour maternal separations over 12 days was also associated with an increase in the severity of withdrawal from chronic morphine, suggesting the development of a greater degree of opiate dependence in animals exposed to early maternal separation. The authors speculate that maternal separation alters morphine sensitivity via stress-induced stimulation of opioid peptides in separated pups, providing additional evidence that early deleterious environmental influences may have an impact on subsequent response to drugs of abuse. Kalinichev, M., Easterling, K.W. and Holtzman, S.G. Early Neonatal Experience of Long-Evans Rats Results in Long-Lasting Changes in Morphine Tolerance and Dependence. Psychopharmacology, 157, pp. 305-312, 2001.

Effects of Aggregating High Risk Youth

This paper focuses on three-year outcomes associated with a preventive intervention trial in which high-risk youth were aggregated into cognitive-behavioral groups. Participants were 158 at-risk youth between the ages of 11 and 14. The participating youth and their teachers were interviewed each year over a three-year period following the intervention. Analyses of covariance and latent growth modeling revealed that the intervention contributed to three-year escalations in self-reported smoking and teacher-reported delinquency. Interactions between participants’ characteristics (i.e., initial status, age, and gender) and intervention were also tested. A statistically reliable interaction was found, suggesting that those with initially low levels of delinquency were especially affected by the peer intervention group. Poulin, F., Dishion, T. J., and Burraston, B. 3-year Iatrogenic Effects Associated with Aggregating High-risk Adolescents in Preventive Interventions. Applied Developmental Science, 5(4), pp 214-224, 2001.

An Integrated Components Preventive Intervention for Aggressive Elementary School Children: The Early Risers Program

The Early Risers prevention program aims to alter the developmental trajectory of children with early onset aggressive behavior that puts them at significant risk of drug use in adolescence. The program features 4 CORE components: (a) an annual 6-week summer school program, (b) a teacher consultation and student mentoring program, (c) child social skills groups, and (d) parent education and skills-training groups, all delivered in tandem with a FLEX family support program individually tailored to address the unique needs of families. At baseline, the mean age of the sample was 6.6 years. Following 2 years of intervention, program children showed significant improvement relative to controls in academic achievement and school behaviors. Change on behavioral self-regulation was moderated by level of child aggression, with intervention effects found for only the most severely aggressive children. Parents with high program attendance rates showed improvement in discipline methods. August, G.J., Realmuto, G.M., Hektner, J.M., and Bloomquist, M.L. An Integrated Components Preventive Intervention for Aggressive Elementary School Children: The Early Risers Program. Journal of Consulting and Clinical Psychology, 69 (4), pp. 614-626, 2001.

Project Towards No Drug Abuse: Generalizability to a General High School Sample

This study examined the generalizability of a successful classroom-based prevention program developed for youth at alternative high schools (high risk) to youth at general high schools. A replication of a previously tested prevention program in a general high school population was conducted with 1-year follow-up data. Classrooms within each of three schools (n =1208) were randomly assigned to two conditions, classroom education or standard care control. Statistically significant effects on alcohol and illicit drug use were achieved in this population through a 1-year period following the program, although effects were not achieved on cigarette smoking and marijuana use. These results suggest that this program (Project Towards No Drug Abuse) has applicability to a wide range of older teens. Preventive Medicine, 32(6), pp. 514-520, 2001.

Session-specific Effects of a Universal Parent-Training Intervention

Preparing for the Drug Free years is a parent training intervention designed to prevent adolescent substance abuse and other problem behaviors. Two hundred nine rural families were randomly assigned to receive the intervention or the wait-list control condition. Analysis of covariance comparing adjusted posttest scores revealed that parents in the intervention condition reported significant improvements in parenting behaviors targeted by specific intervention sessions when compared with controls. Effects were most pronounced among mothers. No significant effects were found for nontargeted parenting behaviors, and targeted behaviors were most improved among parents attending relevant program sessions. These results strengthen the internal validity of the study and increase the plausibility that reported improvements were due to the intervention. Kosterman, R., Hawkins, D.J., Haggerty, K., Spoth, R., and Redmond, C. Preparing for the Drug Free Years: Session-specific effects of a Universal Parent-training intervention with Rural Families. Journal of Drug Education, 31(1), pp. 47-68, 2001.

Modeling Factors Influencing Enrollment in Family-Focused Prevention Intervention Research

This study tests an extension of a previously supported model of family contexts and health belief predictors of parental inclination to enroll in preventive interventions. Model testing was conducted with a sample of 635 parents of 6th graders who completed a prospective participation factors survey and were recruited for an intervention research project six months later. The model fit was strong and all but one of the primary hypothesized effects were supported. Both stated inclination to enroll in an intervention and in the research project had significant positive effects on actual project enrollment occurring 6 months later. Perceived intervention benefits and barriers had significant effects on both types of stated inclination to enroll. Examination of modification indices for the model suggested an additional path linking educational attainment with actual enrollment. Spoth, R., Redmond, C., and Shin, C. Modeling Factors Influencing Enrollment in Family-Focused Preventive Intervention Research. Prevention Science, 1(4), pp. 213-225, 2000.

Long-term follow-up of Brief Family Interventions for General Populations

This study examines the long-term substance use outcomes of two brief interventions designed for general population families of young adolescents. Thirty-three public schools were randomly assigned to three conditions: the 5-session Preparing for the Drug Free Years Program, the 7-session Iowa Strengthening Families Program, and a minimal contact control condition. Assessments included multiple measures of initiation and current use of alcohol, tobacco, and marijuana. The pretest involved 667 6th graders and their families. Follow-up data were collected in the 10th grade. Significant intervention-control differences in initiation and current use were found for both interventions. It is concluded that brief family skills-training interventions designed for general populations have the potential to reduce adolescent substance use. Spoth, R.L., Redmond, C., Shin, C. Randomized Trial of Brief Family Interventions for General Populations: Adolescent Substance Use Outcomes four Years Following Baseline. Journal of Consulting and Clinical Psychology, 69(4), pp. 627-642, 2001.

Preadolescent Predictors of Substance Initiation

This study examines potentially modifiable family and peer factors known to be predictors of early substance initiation. A theoretically derived model of substance initiation was tested using structural equation modeling. Results indicate that both family and peer factors have an impact on early substance initiation when children in this sample were 11 and 12 years old. The model explained 69% of the variance in substance initiation. Prosocial family processes (rules, monitoring, and attachment) had a significant impact on child peer association, decreasing involvement with antisocial peers. These prosocial family processes had a significant negative effect on substance initiation even while modeling the influence of antisocial peers. Oxford, M.L., Harachi, T.W., Catalano, R.F., Abbott, R.D. Preadolescent Predictors of Substance Initiation: A Test of Both the Direct and Mediated Effects of Family Social Control Factors on Deviant Peer Associations and Substance Initiation. American Journal of Drug and Alcohol Abuse, 27(4), pp. 599-616, 2001.

Social Competence and Substance Use Among Rural Youth

Social competence is a construct that has been shown to play a key role in youth development and there has been growth in the study of skills training in social and interpersonal competence in order to prevent drug use, antisocial, and aggressive behavior. This study of 1568 rural junior high school youth was conducted to uncover the mechanisms by which social competence may be associated with substance use during early adolescence. Structural equation modeling indicated that social competence had a direct, protective association with substance use in that those youth who were more socially confident, assertive, and had better communication skills reported less smoking and drinking. Furthermore, the relationship between social competence and substance use was fully mediated by social benefit expectancies of use. Thus, poorly competent youth use cigarettes and alcohol because they perceive that there are important social benefits to these behaviors. Griffin, K.W., Epstein, J.A., Botvin, G.J., and Spoth, R.L. Social Competence and Substance Use Among Rural Youth: Mediating Role of Social Benefit Expectancies of Use. Journal of Youth and Adolescence, 30(4), pp. 485-498, 2001.

Protective Role of Personal Competence Skills in Adolescent Substance Use: Psychological Well-being as a Mediating Factor

Adolescents who use a variety of cognitive and behavioral self-management strategies have been shown to report reduced rates of early-stage substance use, but little is known about how these personal competence skills may be protective. In a series of structural equation models, this study examined the association between competence skills and substance use over a 3-year period among 849 suburban junior high school students, and whether psychological distress, well-being, or both mediated this relation. Findings indicated that well-being fully mediated the relation between early competence and later substance use, but distress did not. Youth with good competence skills reported greater subsequent well-being, which in turn predicted less later substance use. Findings suggest that competence skills protect youth by enhancing well-being and that prevention programs should aim to enhance competence in order to promote resilience. Griffin, K.W., Scheier, L.M., Botvin, G.J., and Diaz, T. Protective Role of Personal Competence Skills in Adolescent Substance Use: Psychological Well-being as a Mediating Factor. Psychology of Addictive Behaviors 15(3), pp. 194-203, 2001.

School-Based Support Groups for Adolescents with an Addicted Parent: Using Principles of Solution Focused Therapy

In every classroom, there are approximately 5 children on average with chemically dependent parents. Few of these children receive supportive services, despite the fact that they attend school less often, are often late for school, and have a higher incidence of learning disabilities. To address this, many school districts offer school-based support groups (SBSG). Consistent with the principles of solution-focused therapy, the SBSG emphasizes the strengths and resiliency of these youth and helps them develop problem-solving strategies and find solutions. This study was a qualitative evaluation of SBSG for adolescents with an addicted parent. Gance-Cleveland, B.L., and Rothman, A. School-Based Support Groups for Adolescents with an Addicted Parent: Using Principles of Solution Focused Therapy. The Drug and Alcohol Professional, 1(1), pp. 17-29, 2001.

A Further Look at the Prognostic Power of Young Children’s Reports of Depressed Mood and Feelings

A primary objective of this study was to determine the validity of first graders’ self-reports of depressed mood and feelings. To that end, the prognostic power of first grade self-reports of depressed mood and feelings was examined with respect to later psychopathology and adaptive functioning in a population of urban school children (N=496). First grade self-reports of depressed mood predicted later child academic functioning, the need for and use of mental health services, suicidal ideation, and a diagnosis of major depressive disorder by age 14. The prognostic power of these early self-reports suggests that children as young as 5 or 6 years of age are capable of providing valid reports of depressed mood and feelings. Ialongo, N.S., Edelsohn, G., and Kellam, S.G. A Further Look at the Prognostic Power of Young Children’s Reports of Depressed Mood and Feelings. Child Development, 72(3), pp. 736-747, 2001.

Child Psychopathology Predicts Heavier Drug Use in Adolescence

The authors examined early psychopathology as a predictor of trajectories of drug use from ages 13-18 years. Six years of annual data were analyzed for 506 boys using a mixed effects polynomial growth curve model. They tested whether distinct measures of psychopathology and behavioral problems (i.e., attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, depression, and violence) assessed in early adolescence could prospectively predict level and change in alcohol and marijuana use. Higher levels of all of the types of psychopathology predicted higher levels of alcohol use, and higher levels of attention-deficit/hyperactivity disorder, conduct disorder, and violence predicted higher levels of marijuana use. Only conduct disorder predicted linear growth in alcohol use, and none of the measures predicted growth in marijuana use. The results suggest that drug use prevention programs should target youths with early symptoms of psychopathology. White, H.R., Xie, M., Thompson, W., Loeber, R., Stouthamer-Loeber, M. Psychology of Addictive Behaviors, 15(3), pp. 210-218, 2001.

Risk Factors for Adolescent Marijuana Use across Cultures and across Time

This integrated analysis of data from 3 different longitudinal studies was conducted to examine the early psychosocial predictors of later marijuana use among adolescents. The data used in the analysis were derived from (a) a sample of 739 predominantly White adolescents representative of the northeastern United States, (b) a sample of 1,190 minority adolescents from the East Harlem section of New York City, and (c) a sample of 1,374 Colombian adolescents from two cities in Colombia, South America. In 2 of the samples, participants were interviewed in their homes, and in the 3rd study, participants were assessed in school. The predictors included a number of variables from (a) the personality domain, reflecting the adolescents' conventionality and intrapsychic functioning; (b) the family domain, representing the parent-child mutual attachment relationship and parental substance use; (c) the peer domain, reflecting the peer group's delinquency and substance use; and (d) the adolescents' own use of legal drugs. The dependent variable was adolescent marijuana use. The results of the analysis demonstrated remarkable consistency in the risk and protective factors for later marijuana use across the 3 samples, attesting to the robust nature of these predictors and their generalizability across gender, time, location, and ethnic/cultural background. These findings have important implications for designing intervention programs. Programs aimed at preventing adolescent marijuana use can be designed to incorporate universal features and still incorporate specific components that address the unique needs of adolescents from different groups. Brook, J.S., Brook, D.W., Arencibia-reles, O., Richter, L., and Whiteman, M. J Genet Psychol, 162(3), pp. 357-374, 2001.