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2017 March

Intervention Development for Teen Alcohol Use: A Multi-Method and Daily Diary Examination of Substance-free Activities and High-risk Alcohol Use.

Jennifer M. Cadigan, PhD
Postdoctoral Fellow

Center for the Study of Health and Risk Behaviors, Psychiatry & Behavioral Sciences

Christine Lee, PhD, Research Professor (Mentor),
Center for the Study of Health and Risk Behaviors, Psychiatry & Behavioral Sciences

Description: Adolescent alcohol use is associated with limited academic performance, career aspirations, adult role attainment, and less engagement in substance-free activities. Brief substance use interventions for college students have been enhanced using a behavioral economic supplement (Substance-Free Activity Session; SFAS). The SFAS behavioral economic supplement aims to increase the salience of delayed academic and career goals, increase engagement in substance-free activities, and increase the salience of both short and long-term goals in the context of existing alcohol and other substance use. Less is known how high school students spend their time, what substance-free activities they engage in and view as attractive and acceptable, and how goals impact their substance use.

This project aims to design a developmentally tailored adolescent alcohol SFAS intervention using an iterative treatment development process of daily diary phase and an intervention refinement phase. Utilizing a stage model for intervention development guidelines, the proposed project aims to adapt a novel SFAS intervention for high school students. The proposed project will use event-level daily diary methods to characterize how high school students spend their time in relation to substance use and goals, specifically examining temporal precedence of substance-free activities, time allocation, and substance use (Aim 1), and examine the satisfaction and acceptability of the SFAS for high school students with an intervention refinement phase (Aim 2). Findings from the etiologic investigation of Aim 1 will inform the design of the modified intervention that is developmentally tailored to suit an adolescent population.

This project will inform research on prevention and intervention approaches for adolescent alcohol use and serve as pilot data for a randomized clinical trial.

Piloting of a Synthetic Control Approach for Assessing Impact of Changes in State Marijuana Policy on Adolescent Substance Use and Related Behaviors.

Katarina Guttmannova, Ph.D.
Assistant Professor

Center for the Study of Health and Risk Behaviors, Psychiatry & Behavioral Sciences

Charles B. Fleming, M.A. (Co-Investigator)
Center for the Study of Health and Risk Behaviors, Psychiatry & Behavioral Sciences

Description: This project will capitalize on existing nationwide state-level data to examine whether state-level marijuana policies affect marijuana and other drug use by youth and related negative consequences of use such as mental health problems and violence. As more states loosen their marijuana-related policies, understanding the effects of these changes in marijuana laws on youth development is critical. Existing evidence regarding the effects of marijuana policies on adolescent outcomes remains mixed.

A number of factors could account for this. Marijuana policies, although easily distinguished by whether they concern medical and recreational marijuana legalization (MML and RML, respectively), vary within these 2 categories across states and within states over time, and extant studies have varied in their definition of policy change under evaluation. Further, studies have differed on comparison groups used to contrast trends before and after policy change, applying counterfactuals that may not be sufficiently equivalent.

The proposed study will pilot an innovative analytic technique, synthetic control modeling, to compare trends in adolescent outcomes from an early adopting MML state with a weighted counterfactual based on data from states that that did not pass such policy but are similar in pre-policy levels of relevant covariates and outcomes. This work will provide critical information to guide planning of prevention and intervention efforts aimed at reducing adolescent problem behaviors in the changing marijuana policy context. It will also increase the research team’s competitiveness for obtaining funding to more widely apply the synthetic control approach to evaluating the effects of marijuana policy.

2017 October

Phasic Dopamine Release in the Nucleus Accumbens Core Differentially Alters Drug-taking and Drug-seeking

Ryan D. Farero
Predoctoral Fellow

Psychiatry & Behavioral Sciences

Paul E. M. Phillips, PhD (Mentor)
Psychiatry & Behavioral Sciences; Pharmacology

Description: Alterations in dopamine transmission have been implicated in most contemporary theories of drug addiction. However, the manner and even the direction of these alterations are quite controversial. Dopamine within the nucleus accumbens core mediates the motivation to seek drug elicited by drugassociated cues. Interestingly, dopamine within the nucleus accumbens core has also been demonstrated to be involved in producing drug-satiety, and thus regulating drug intake.

Recent work in our lab has demonstrated that phasic dopamine transmission in response to drug-associated cues, has diametric changes as animals transition into excessive drug-use (see Fig. 1). These diametric phasic dopamine signals appear to rely on the manner in which the drug-associated cue is presented. For instance, when drug-associated cues are presented non-contingently, or non-reliant, on an animals behavior, phasic dopamine transmission increases, and coincides with drug-seeking behavior. Whereas, when drug-associated cues are presented as a result of an animal’s behavior, or response-contingent, the phasic dopamine signals elicited by the drug-associated cue attenuate in animals whom have transitioned into excessive or escalated drug-consumption. Pharmacologically increasing dopamine through administration of L-DOPA, a pre-cursor of dopamine, decreases an animal’s drug-consumption back to pre-escalated levels, or prevents escalation from occurring. Due to this observed divergence in dopamine transmission in response to drug-associated cues, we hypothesize that nucleus accumbens core phasic dopamine transmission is differentially mediating escalation of drug-taking, and drugseeking.

This proposal seeks to investigate this hypothesis by manipulating dopaminergic terminals in the nucleus accumbens core during drug-taking and drug-seeking behavioral assays. This will be achieved by utilizing optogenetic viral vector targeting to express both excitatory and inhibitory photogated ion channels into dopaminergic terminals. This data would reveal a causal relationship between nucleus accumbens core dopamine signaling alterations and both escalation of drug-consumption and drug-seeking behaviors, two distinct, but equally important hallmarks of drug addiction.

It Works. Now How Can We Get Them to Come? Development, Feasibility, and Acceptibility of Strategies for Engagement and Participation of Young Adults in the General Community in a Brief Alcohol Intervention

Christine M. Lee, PhD.
Research Professor

Psychiatry & Behavioral Sciences

Chethana Achar, MBA (Co-Investigator)
Graduate Student, Foster Business School

Description: Alcohol use, misuse, and resulting negative consequences among young adults has been extensively documented. While there are effective interventions for young adult alcohol use, there remains a gap between interventions developed and tested within the context of a randomized clinical trial and application in the real world where the intervention is utilized without monetary incentive for participation in baseline and longitudinal assessment. It is clear that while many young adults engage in high-risk alcohol use, with the majority non-treatment seeking, young adults may also benefit from indicated prevention strategies. The question remains how to best engage and recruit these young adults in the general community to a program designed to meet their needs without the resources of a randomized clinical trial to pay young adults for their time.

The goal of this pilot study is to develop and test the feasibility and acceptability of a comprehensive marketing strategy to engage young adults in the community to participate in a program that screens for high-risk alcohol use and either provides personalized normative feedback for those not meeting high-risk criteria or for those who do, a brief personalized feedback intervention for reducing high-risk alcohol use.

This application brings together investigators with expertise on young adulthood, alcohol use, and marketing to develop and examine the feasibility and acceptability of various marketing strategies to engage a community sample of young adults to participate in an alcohol intervention program, which involves screening, brief prevention messages, and for those in need, a brief alcohol web-based intervention. Funds from this ADAI small grant will be instrumental in documenting ongoing collaboration, feasibility of engaging and “recruiting” young adults to participate in the program, and providing initial data on acceptability of various marketing strategies.

Mobile Detection of Opioid-Induced Respiratory Depression

Jacob Sunshine, MD, MS
Assistant Professor

Anesthesiology & Pain Medicine

Shyamnath Gollakota, PhD (Co-Investigator)
Associate Professor, Computer Science & Electrical Engineering

Description: A fundamental challenge of the opioid epidemic is that overdose victims die because they are alone or among untrained or impaired bystanders. Yet these deaths are completely preventable with early detection and appropriate supportive care.

The overall objective of this specific proposal is to evaluate whether an existing, clinically validated, contactless respiratory sensing software on a commodity smartphone can be modified to reliably detect the hallmark clinical sign that precedes fatal opioid overdose, opioid-induced respiratory depression. If clinically significant opioid-induced respiratory depression can be objectively identified in out-of-hospital environments, and nearby bystanders or EMS are notified, it has the potential to significantly reduce morbidity and mortality associated with opioid overdoses. The investigational software has already achieved highly promising results measuring respiration in the sleep lab setting and acute apnea events in the operating room during induction of general anesthesia; we propose to test the software in a real-world opioid use environment where people experience real-world opioid-induced respiratory depression in a safe setting. This unique setting is a Supervised Injection Facility (SIF), where users self-inject opioids under supervision of trained clinical staff.

We have received permission from a SIF in Vancouver, BC, Insite, to collect these necessary (and difficult to obtain) data to modify the software to reliability detect opioid-induced respiratory depression. At the completion of this feasibility pilot, we expect to have enough training data to finalize the software for use in the opioid-use setting, at which point it would be ready for a formal, adequately powered real-world diagnostic accuracy study, which would also take place at Insite. This project is clinically important because it will provide key data needed to develop a low cost, ubiquitous technology capable of identifying and anticipating acute drug overdose events in out-of-hospital environments, with the ability for real-time notification of nearby bystanders and EMS.

2017 September I-502 Funds

Brain and Behavioral Correlates of Prenatal Marijuana Exposure

Natalia Kleinhans, PhD, Associate Professor

Co-Investigator: Stephen Dager, MD, Professor, Radiology, and Associate Director, Center on Human Development and Disability (CHDD)

Description: Cannabis use during pregnancy has increased substantially, in conjunction with widespread decriminalization/legalization, changing public perceptions about harm, and evidence of cannabis’s antiemetic properties. Prior outcomes research on prenatal marijuana exposure is narrow in scope and may have limited relevance to medicinal users, as these older studies included research participants with polysubstance use (e.g. tobacco, alcohol, illicit drugs). In addition, prior research also likely underestimated potential risks of cannabis use during pregnancy because modern strains are 3 times more potent than they were 30 years ago. We propose to study brain development in infants exposed in utero to cannabis using state-of-the-art MRI and comprehensive questionnaires that we have validated in our studies of infants at high-risk for developing autism spectrum disorder. Cutting-edge neuroimaging techniques have been shown to identify brain changes and subtle behavioral differences before outward symptoms are visible. By focusing on infancy, we aim to characterize cannabis-induced brain and behavioral changes while minimizing environmental effects that contribute to outcomes at older ages.

We will recruit 5 mother-infant pairs (where the mother used cannabis to alleviate morning sickness) and 5 mother-infant control pairs (where the mother was prescribed medication for morning sickness). Infants will undergo multi-modal imaging (functional magnetic resonance imaging, magnetic resonance spectroscopy, and diffusion tensor imaging) under natural sleep at 6 months-of-age. Pilot data obtained through the ADAI mechanism will be combined with a small data set (N=10) obtained with internal department of Radiology funds.

These funds will position the principal investigator to generate preliminary data for an R01 proposal that is responsive to NIDA PA-14-163, “Effects of Cannabis Use and Cannabinoids on the Developing Brain” focused on longitudinal brain changes and extensive measures of cognitive and emotional development in babies exposed to marijuana in utero.

Cannabis Identity as a Cognitive Risk Factor for Young Adult Cannabis Misuse

Jason Ramirez, PhD, Acting Assistant Professor
Psychiatry & Behavioral Sciences

Co-Investigators: Christine Lee, PhD, and Kristen Lindgren, Psychiatry & Behavioral Sciences

Description: Cannabis misuse is associated with numerous negative consequences and is a growing public health concern given increases in misuse in the past decade. Recent theoretical models assert that substance identity, or the extent to which one views substance use as part of their self-concept, is a unique and important cognitive risk factor for substance misuse. Substance-related identities can be measured with explicit (e.g., self-report) and implicit (e.g., reaction time) measures; and both uniquely predict substance misuse.

To date, research on cannabis identity is limited as reliable implicit measures have yet to be developed and explicit measures require validation as unique predictors of cannabis misuse. The proposed research aims to address these gaps and has two phases: Phase 1) 30 young adults in Washington that regularly use cannabis will attend focus groups to discuss identification with cannabis. Themes from focus groups will be disseminated as a qualitative manuscript and will inform stimuli development for two novel Cannabis Identity Implicit Associations Tests (CI-IATs) to assess implicit cannabis identity. Phase 2) 120 young adults will complete two online assessment batteries separated by three months that include the CI-IATs, an explicit measure of cannabis identity, and self-reported cannabis use, misuse, and descriptive norms of cannabis use. A subset of 60 participants will complete a third assessment to examine the test-retest reliability of implicit and explicit cannabis identity measures. Implicit and explicit measures of cannabis identity will be examined as unique predictors of current and prospective cannabis misuse.

The ultimate goals of this application are to establish whether cannabis identity is a unique cognitive risk factor for cannabis misuse, to advance theory, and to provide pilot data for a future R01 proposal to examine longitudinal relationships between cannabis identity and cannabis misuse among young adults

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