Matrix Institute on Addictions

Prior research has demonstrated the scope and impact of adverse childhood experiences (ACEs) on health and wellbeing. Less is known about the trajectories from exposure to ACEs, such as witnessing family conflict and violence in the community, to teen dating violence perpetration, and the protective factors that buffer the association between early exposure to ACEs and later teen dating violence perpetration. Students (n = 1611) completed self-report surveys six times during middle and high school from 2008 to 2013. In early middle school, the sub-sample was 50.2% female and racially/ethnically diverse: 47.7% Black, 36.4% White, 3.4% Hispanic, 1.7% Asian/Pacific Islander, and 10.8% other. Youth were, on average, 12.7 years old. Latent transition analysis was used to assess how trajectories of exposure to parental conflict and community violence during middle school transition into classes of teen dating violence perpetration (e.g., sexual, physical, threatening, relational, and verbal) in high school. Protective factors were then analyzed as moderators of the transition probabilities. Three class trajectories of ACEs during middle school were identified: decreasing family conflict and increasing community violence (n = 103; 6.4%), stable low family conflict and stable low community violence (n = 1027; 63.7%), stable high family conflict and stable high community violence (n = 481; 29.9%). A three class solution for teen dating violence perpetration in high school was found: high all teen dating violence class (n = 113; 7.0%), physical and verbal only teen dating violence class (n = 335; 20.8%), and low all teen dating violence class (n = 1163; 72.2%). Social support, empathy, school belonging and parental monitoring buffered some transitions from ACEs exposure trajectory classes to teen dating violence perpetration classes. Comprehensive prevention strategies that address multiple forms of violence while bolstering protective factors across the social ecology may buffer negative effects of exposure to violence in adolescence.

BackgroundDeveloping efficacious medications to treat methamphetamine dependence is a global challenge in public health. Topiramate (TPM) is undergoing evaluation for this indication. The molecular mechanisms underlying its effects are largely unknown. Examining the effects of TPM on genome-wide gene expression in methamphetamine addicts is a clinically and scientifically important component of understanding its therapeutic profile.MethodsIn this double-blind, placebo-controlled clinical trial, 140 individuals who met the DSM-IV criteria for methamphetamine dependence were randomized to receive either TPM or placebo, of whom 99 consented to participate in our genome-wide expression study. The RNA samples were collected from whole blood for 50 TPM- and 49 placebo-treated participants at three time points: baseline and the ends of weeks 8 and 12. Genome-wide expression profiles and pathways of the two groups were compared for the responders and non-responders at Weeks 8 and 12. To minimize individual variations, expression of all examined genes at Weeks 8 and 12 were normalized to the values at baseline prior to identification of differentially expressed genes and pathways.ResultsAt the single-gene level, we identified 1054, 502, 204, and 404 genes at nominal P values < 0.01 in the responders vs. non-responders at Weeks 8 and 12 for the TPM and placebo groups, respectively. Among them, expression of 159, 38, 2, and 21 genes was still significantly different after Bonferroni corrections for multiple testing. Many of these genes, such as GRINA, PRKACA, PRKCI, SNAP23, and TRAK2, which are involved in glutamate receptor and GABA receptor signaling, are direct targets for TPM. In contrast, no TPM drug targets were identified in the 38 significant genes for the Week 8 placebo group. Pathway analyses based on nominally significant genes revealed 27 enriched pathways shared by the Weeks 8 and 12 TPM groups. These pathways are involved in relevant physiological functions such as neuronal function/synaptic plasticity, signal transduction, cardiovascular function, and inflammation/immune function.ConclusionTopiramate treatment of methamphetamine addicts significantly modulates the expression of genes involved in multiple biological processes underlying addiction behavior and other physiological functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-014-0065-x) contains supplementary material, which is available to authorized users.

To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. ClinicalTrials.gov identifier: NCT01077024.

This longitudinal study of substance abuse treatment in residential and outpatient settings examines substance abuse treatment under managed care insurance, and compares client characteristics, processes, and outcomes of substance abuse treatment, by gender and ethnicity. At baseline, the women in the study (N = 69), compared to men (N = 91), were on more psychotropic medications, had higher scores for drug dependency, and lower quality of life scores, including symptomatology and functional status. Women also had higher drug use scores before treatment than men, and fewer days of sobriety; after treatment there were no significant differences between women and men. Although these women were more affected by their substance abuse than men at baseline, the differences were eliminated by follow-up.At baseline, Caucasians (N = 103) used more psychotropic medications than Hispanics. Additionally, Caucasians had higher functional status and total quality of life compared to non-Caucasians (Hispanic and African...

Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine–antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effectiveness in clinical research and the implications of research for the health care delivery system. Although a rationale for CAP can be developed from receptor pharmacology, there is little available preclinical research testing these concepts in animal models. Randomized clinical trials of CAP show minimal or no benefit for overall severity of symptoms. Most studies at the level of health services are limited to estimates of CAP prevalence and some suggestion of increased costs. Increasing use of antipsychotic polypharmacy in general may be a factor contributing to the under-utilization of clozapine and long delays in initiating clozapine monotherapy. Translational research models can be applied to clinical questions such as the value of CAP. Better linkage between the components of translational research may improve the appropriate use of medications such as clozapine in psychiatric practice.

Methamphetamine, called meth, crystal, or speed, is a central nervous system stimulant that can be injected, smoked, snorted, or ingested orally; prolonged use at high levels results in dependence. Methamphetamine (MA) is a derivative of amphetamine, which was widely prescribed in the 1950s and 1960s as a medication for depression and obesity. reaching a peak of 31 million prescriptions in the United States in 1967. Until the late 1980s. illicit use and manufacture of MA was endemic to California, but the MA user population has recently broadened in nature and in regional distribution, with increased use occurring in midwestern states. An estimated 4.7 million Americans (2.1% of the U.S. population) have tried MA at some time in their lives. Short-and longterm health effects of MA use include stroke, cardiac arrhythmia, stomach cramps, shaking, anxiety, insomnia, paranoia, hallucinations, and structural changes to the brain. Children of MA abusers are at risk of neglect and abuse, and the use of MA by pregnant women can cause growth retardation. premature birth, and developmental disorders in neonates and enduring cognitive deficits in children. MA-related deaths and admissions to hospital emergency rooms are increasing. Although inpatient hospitalization may be indicated to treat severe cases of long-term MA dependence, optimum treatment for MA abusers relies on an intensive outpatient setting with three to five visits per week of comprehensive counseling for at least the first three months. The burgeoning problems of increased MA use must be addressed by adequate treatment programs suitable for a variety of user types.

The Methamphetamine Treatment Program (MTP), funded by the Center for Substance Abuse Treatment, has the objectives of implementing the Matrix outpatient model and evaluating that model in comparison to the existing community “treatments as usual.” Seven organizations in three western states (California, Montana, and Hawaii) were selected to participate in this randomized, controlled, multisite project in what constitutes the largest trial to date of treatment for methamphetamine (MA) dependence. One hundred fifty MA-dependent patients recruited at each site are randomly assigned to receive either the Matrix model, a manualized program of intensive outpatient treatment, or the site's standard treatment, “treatment as usual.” Participants are evaluated at admission, weekly during treatment, at the time of scheduled discharge. and at six and 12 months after admission. Dependent measures assess changes in drug use, HIV risk behaviors, quality of life. and patient satisfaction. Cost analyses to quantify treatment costs and determine the association between costs and clinical outcomes will be conducted. A number of adjustments in the original study design have been necessitated by the realities of community sites' strengths and limitations. Experiences from this multisite project will also provide a model for other efforts to transfer researchbased treatments into community settings. This article describes the main aims of the project, the background and rationale for the study design, a brief description of the research plan, and methods implemented to protect the integrity of the science.

Data from a four-wave panel design of 975 adolescents were used to study inter-relationships among suicidal behaviors, depressive symptoms, and substance use behaviors. Persistently high levels of problem drinking and depressive symptoms were associated with higher levels of suicidal thoughts and attempts. Higher levels of depressive symptoms and greater cigarette and illicit drug use distinguished suicidal ideators from attempters. Adolescents attempting suicide reported lower levels of family social support, a greater use of substances to cope with stressors, and a higher density of substance-using peers. Implications of the findings for preventive interventions with high-risk teens are discussed.