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2016 March I-171 Funds

Characterization of Calcium Signaling in Striatal Cell Populations following Cocaine Use

Susan Ferguson, PhD, Assistant Professor
Psychiatry & Behavioral Sciences

Description: Drug addiction is marked by a transition to compulsive drug-taking characterized by a loss of control over intake, high motivation to obtain drug, use despite negative consequences, and a high propensity to relapse. Although only a subset of individuals that try drugs will develop this pathological behavior, treatment options are limited. Elucidating the neurobiological changes underlying addiction, therefore, is critical to therapeutic development. Alterations within the cortico-basal ganglia-thalamic circuit contribute to the development of addiction. Medium spiny projection neurons (MSNs) within the striatum serve as the primary relay station of this circuit, and guide behavioral output through two divergent pathways (the direct and the indirect). Direct pathway MSNs (dMSNs) can act as a ‘go’ signal to facilitate behaviors whereas indirect pathway MSNs (iMSNs) can act as a ‘brake’ to inhibit behaviors. Although there is now evidence that dMSNs and iMSNs may differentially regulate psychostimulant- induced behaviors, this work has mostly utilized non-contingent drug administration. Consequently, how the activity of these striatal cell populations is altered in individuals displaying compulsive drug use using paradigms that more closely mimic the human condition, such as drug self-administration, are unclear.

The overall goal of this proposal is to begin to address this question by utilizing ex-vivo two- photon calcium imaging to examine activity patterns in dMSNs and iMSNs following drug use in a rodent model of cocaine addiction. We hypothesize that drug use that results in an addiction-like phenotype is driven by a change in the balance of activity of dMSNs and iMSNs, with a net shift in activity towards the ‘go’ signal. This work has the potential to identify critical shifts in activity patterns in animals displaying different patterns of drug use, which could have a big impact on refining the targets for treatments aimed at reversing addictive behaviors, as well as developing new screening tools for at- risk individuals.

A Measurement Burst Study of the Prototype Willingness Model among Adolescents

Melissa A. Lewis, PhD, Associate Professor
Psychiatry & Behavioral Sciences

(Co-Investigator: Anne Fairlie, PhD, Acting Assistant Professor; Christine Lee, PhD, Research Associate Professor; Dana M. Litt, PhD, Assistant Professor, all from Psychiatry & Behavioral Sciences

Description: Alcohol use, misuse, and resulting negative consequences among adolescents have been extensively documented; however, research focusing on Prototype Willingness Model decision-making cognitions using ecological momentary assessment (EMA) data for adolescents is limited. The proposed research will provide the first daily-level test of the Prototype Willingness Model, examining the effects of decision-making cognitions on high-risk alcohol use and related negative consequences using measurement burst EMA among adolescents aged 15-18. In this proposal, we will collect pilot data for a R01 NIAAA project: A Longitudinal, Measurement Burst Study of the Prototype Willingness Model and Adolescent High-Risk Drinking Behavior (PI: Melissa A. Lewis, R01AA024719).

In this pilot study, we will recruit an adolescent sample to evaluate event-level associations using three bursts of weekly assessments. The pilot study will consist of a total of 33 assessments (11x/week for three weeks) among 75 adolescents aged 15-18. The results of the pilot study will allow us to examine psychometric properties of daily measures to inform the R01 as well as demonstrate the ability to conduct measurement burst EMA among adolescents for Prototype Willingness Model cognitions. Daily process mechanisms allow greater insight into factors contributing to increased risk in-the-moment, which may point to targets for interventions (e.g., text interventions) aimed at improving adolescents’ ability to make healthier choices in moments when they may be at greater risk for engaging in risky behaviors. This study has high impact potential to extend the literature on adolescent drinking decision-making processes as well as to directly address reviewer comments made during the original submission of the R01 to NIH.

Resulting articles & projects:

  • Pilot data from this project, including the screening data, was used for two NIH grants currently under review (October 2017):
    1. A Longitudinal, Measurement Burst Study to Examine the Ecological Validity of the Prototype Willingness Model of Hazardous Young Adult Alcohol Use. ROI application to NIAAA; PI: Melissa A. Lewis
    2. Development and Pilot of Preventative Intervention Targeting Online and Offline Social Influence to Reduce Young Adult Social Networking Site Drinking Cognitions and High-Risk Alcohol Use. R34 application to NIAAA; PI: Melissa A. Lewis

Characterizing Auditory Processing in Individuals with Fetal Alcohol Spectrum Disorder

Susan McLaughlin, PhD, Research Scientist
Institute for Learning & Brain Sciences

Co-Investigators: Adrian KC Lee, ScD, Associate Professor, Speech & Hearing Sciences; Susan Astley, PhD, Professor, Department of Epidemiology & Pediatrics

Description: The purpose of the proposed work is to assess, for the first time, the presence of central auditory processing deficits in individuals with Fetal Alcohol Spectrum Disorders (FASD) and to begin to disentangle the neural processing levels at which such auditory impairments occur. A limited but growing body of research suggests that the teratogenic effects of prenatal alcohol exposure include insults to the auditory system, potentially at the periphery (i.e., the middle and inner ear) and also in the brain. An elaborate hierarchy of auditory processing operations takes place in the brain which are crucial to the ability to hear and attend to sound targets in the presence of noise. In the complex acoustic environments common to daily life (e.g., classrooms, restaurants), this capacity is essential for speech perception, and central auditory processing deficits that result in impaired sound-in-noise listening (even in the absence of peripheral hearing loss) have the potential to critically disrupt acquisition of fundamental language skills.

We hypothesize that some of the communication impairments typically reported in FASD may be related in part to such auditory deficits, and that – in the large percentage of individuals with FASD but without the craniofacial dysmorphia of full-blown FAS (Fetal Alcohol Syndrome) – these deficits are more central than peripheral in nature. The current project will apply rigorous psychoacoustic and electroencephalography assays to 1) precisely assess sound-in-noise listening abilities and 2) functionally characterize the integrity of the central auditory pathway, from brainstem to cortex in individuals with FASD. This research has both potential clinical implications in its power to reveal the contribution of auditory sensory-related deficits to communication impairments common in FASD, thereby informing improved intervention strategies, and theoretical, in its capacity to extend understanding of central auditory processing deficits and their impact on behavior across a variety of neurodevelopmental disorders.

Increasing Knowledge and Access to HIV Pre-Exposure Prophylaxis among Methamphetamine-using Men who have Sex with Men: A Mixed-Methods Approach

Joanne Stekler, MD, MPH, Associate Professor
Allergy & Infectious Diseases

Vanessa McMahan, Research Coordinator

Description: There is an urgent need to find ways to successfully target HIV prevention strategies to men who have sex with men (MSM) who use methamphetamine (meth). Meth-using MSM are at particularly high risk for HIV acquisition. Public Health – Seattle King County (PHSKC) has estimated that MSM who use meth are 5 times more likely to be diagnosed with HIV than non-meth using MSM. Daily, oral pre- exposure prophylaxis (PrEP) with Truvada is a highly-efficacious strategy for the prevention of HIV in adults; however, despite overall high interest in PrEP among MSM, there is a smaller than expected number of meth-using MSM who are enrolling in local PrEP programs. It is critical to understand the knowledge and access to PrEP, and motivations for and concerns about its use, among meth-using MSM in Seattle to better target PrEP delivery to this population.

There is a strong evidence base for the effectiveness of peer interventions in the field of HIV. Our prior research includes facilitating a focus group with the peer educators at Project NEON, an HIV prevention program that works with MSM who are active meth users or in recovery. The peer educators emphasized that there are barriers to PrEP that are specific to meth users, including competing priorities (e.g., getting high); difficulties complying with appointments and medication adherence; and concomitant wellness and social concerns, notably depression and stigma.

There is a paucity of educational materials about PrEP targeted to meth-using MSM and it is critical that information and resources to link this population to PrEP are developed. In order to ultimately increase PrEP use among meth-using MSM at high risk for HIV in Seattle, we propose to further explore their knowledge and access to PrEP, fill identified gaps in information among the peer educators, and develop targeted educational materials.

The proximal objective of this proposal is to assess the knowledge and opinions about pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) who use methamphetamine (meth) in Seattle and to develop targeted educational materials about the safety, effectiveness, and appropriate use of PrEP for this community. The ultimate objective of this work is to increase PrEP use among HIV-negative MSM who use meth and are at risk for HIV acquisition. To do so, this application proposes to focus on the development of the peer educators at Project NEON, as opinion leaders and educators in the local meth-using MSM community, to promote and facilitate access to PrEP in their networks. The findings from the proposed study will inform existing and future programs to successfully target PrEP to HIV-negative meth-using MSM.

Resulting articles & projects:

  • Based on this preliminary work, Dr. Stekler received funding for an R34 NIH R34 DA 045620-01 (August 2017-June 2020, $450,000 total direct costs) entitled: “Interventions to Improve the HIV PrEP Cascade among Methamphetamine Users”. The R34 will evaluate the feasibility and acceptability of a text messaging and peer navigation intervention to support MSM/TG who use meth and seek PrEP at two clinics in Seattle. Educational materials developed under the ADAI small grant will be refined and used for this project. We are currently developing additional trial materials and refining the interventions through formative work with community partners and members, and plan to start recruiting in March 2018.
  • McMahan V, Martin A, Garske L, Baeten JM, Banta-Green C, Stekler J. Knowledge about PrEP among MSM and Trans* Methamphetamine Users in Seattle. 24th Conference on Retroviruses and Opportunistic Infections; Seattle, WA; February 13-16, 2017. Abstract no. 967.

2016 March I-502 Funds

An Investigation of Craving and Cannabis Misuse among Young Adults Using Multiple Levels of Analysis

Matthew C. Enkema, Graduate Student
Psychology

Mentor: Mary E. Larimer, PhD, Professor, Department of Psychiatry & Behavioral Sciences and Professor and Department of Psychology

Description: Cannabis misuse is a behavior associated with substantial negative life outcomes and is a growing public health concern. Epidemiology indicates cannabis misuse peaks during young adulthood, which has been identified as an important developmental period for intervention. Many young adults use cannabis to cope with unpleasant momentary experiences, and those who do frequently experience more substantial negative cannabis-related and mental health consequences. Based on behavioral theory, and the allostatic model (or self-medication hypothesis), current treatments for substance misuse which incorporate a focus on improving craving management, or adjusting peoples' avoidant relationship with unpleasant momentary experiences such as craving and negative affect, have reported positive outcomes.

The current proposal will investigate cross-sectional retrospective and momentary measures of craving and affect as predictors of cannabis use among young adults (Aim 1). In addition, this study will investigate hypothesized retrospective moderators to identify craving management variables (or psychological factors that affect responses to craving) that influence the relationship between craving and use (Aim 2). Finally, this study will use multilevel modeling to evaluate hypothesized momentary craving management variables that influence the relationship between momentary craving and subsequent use, as well as investigate craving as a mediator of the association between implicit risk factors and cannabis use (Aim 3). One team of investigators has reported a positive relationship between momentary craving and subsequent use among young adult cannabis users. Results from this program of research will investigate this relationship further, and enhance current prevention and treatment efforts by providing important information about craving-related variables that may influence the development and maintenance of cannabis misuse during young adulthood.

Resulting articles & projects:

  • Enkema M, Larimer M, Hallgren K, Lindgren K, Bowen S. "Patterns of Cannabis Use, Related Problems, and Readiness to Change among Young Adult College Students." Presented at the 79th Annual Scientific Meeting of the College of Problems on Drug Dependence, Montreal, June 17-22, 2017.
  • The pilot work in this project formed the basis for a funded NIDA grant to Dr. Enkema: "An Investigation of Craving and Cannabis Misuse among Young Adults Using Multiple Levels of Analysis" (5F31DA042503-02). Details in NIH Reporter

Consumers’ Perspectives on the Function of Marijuana in Their Lives

Robin M. Harwick, PhD, Research Scientist
Alcohol and Drug Abuse lnstitute

Co-Investigators: N. Tatiana Masters, PhD, Research Scientist, ADAI; Beatriz Carlini, PhD, Research Scientist, ADAI

Description: The dichotomy between medicinal and recreational marijuana present in Washington state law reflects the way US science and policy have approached marijuana use for many decades. However, recent research suggests that boundaries between these two types of marijuana use - firmly delineated in public policies - seem quite blurred to consumers. In both clinical and community samples, medical and non-medical marijuana consumption often overlap, and consumers may transition over time from medical to non-medical use or vice-versa. Lines between these types of cannabis consumption may soon blur further as Washington law requires medical marijuana dispensaries to close and the medical system is merged into non-medical retail. This proposal aims to understand cannabis consumption from the perspective of adult regular users, without preconceived ideas that their use is defined by current categories of medicinal or recreational (non-medical). Using grounded theory and qualitative methods of data collection, its purpose is to understand marijuana consumption styles from the ground up. Participants who define themselves as regular marijuana consumers will be recruited for focus groups. Groups (6 total of 6-10 people each) will be recorded and transcribed for analysis. In them, participants will share their perspectives on marijuana's functional utility to them along with their different motivations, settings, and contexts for consumption. Qualitative data analyses informed by grounded theory will be used to produce a taxonomy of how these adults perceive marijuana's function(s) in their lives. Results will delineate cannabis consumption styles and functions described in consumers' accounts, relationships among these styles within participants, and the proportion of each consumption style across participants. Knowledge acquired can be used in shaping research, policies, and treatment related to marijuana consumption. Findings will also inform future grant applications on the development of marijuana consumption survey questions and measures that are valid, reliable, and standardized.

The overall objective of this study is to generate a taxonomy of how adults who regularly consume marijuana perceive its function in their lives. In particular, this study will use grounded theory to understand the phenomenon of marijuana consumption from the consumer's perspective, potentially broadening the framework beyond the binary categories of medical vs non-medical cannabis.

Resulting articles & projects:

  • Harwick R, Masters T, Carlini B. “Consumers’ Perspectives on the Function of Cannabis in their Lives.” Presentation at the Institute of Cannabis Research Conference. Pueblo, CO, April 2017.
  • Harwick R, Carlini B, Masters T. A taxonomy of consumers’ perspectives on the function of cannabis in their lives. (submitted for publication 2017)

Linking Sight and Smell: fMRI Correlates of Marijuana Craving in Adults

Natalia Kleinhans, PhD, Associate Professor
Radiology

Co-Investigators: Mary Larimer, PhD, Professor, Department of Psychiatry & Behavioral Sciences and Department of Psychology

Description: Approximately 15% of adults in the state of Washington use marijuana and of those, an estimated 9% will become dependent on it. Craving is a harbinger that can signal the transition from recreational drug use to problematic, compulsive, drug taking behavior. Presenting individuals with cues associated with marijuana use can induce craving in an experimental setting, and is a powerful approach for studying the neural correlates of addiction and relapse. Cue-reactivity research utilizing marijuana cues is underdeveloped, especially in comparison to other drugs such as cocaine, tobacco, heroin, and alcohol.

The purpose of this study is to develop a new, multisensory marijuana cue-reactivity paradigm using olfactory stimuli. Exposure to the smell of cannabis is a universal component of typical marijuana use and, thus, may be less sensitive to individual differences in a user’s particular habits. In addition to assessing the neural substrates of marijuana cue-reactivity, we will also evaluate the relationship between fMRI activation and subjective craving/reward measures and an objective measure of marijuana use following cue exposure. We will recruit 20 participants with a DSM-V-defined marijuana use disorder and 20 cannabis-naïve participants who do not have a history of any substance use disorder. Participants will undergo fMRI scanning and complete behavioral measures related to substance use. In addition, data will be collected on the amount of marijuana used within the first 24 hours following the fMRI craving experiment. Pilot data obtained through this mechanism will position the principal investigator to expand her program of research into addictions, and generate preliminary data to include in a R01 proposal focused on encoding multisensory cues that trigger drug craving, drug-seeking and relapse

Resulting articles & projects:

  • Data from this project is being used for additional grant submissions. Imaging data collected under this award was used in R01 & R21 submissions to fund the study of infant brain development following the anterior cingulate prenatal exposure to maternal cannabis use. Data from this award is also being used to support an R01 application to assess patterns of marijuana use and associated neural effects in a population with mild traumatic brain injuries.
  • Data analysis and manuscript writing is underway; completion is anticipated in Fall 2017 of a manuscript assessing white matter integrity and how it relates to cannabis use history, including age at first use and years of frequent use.

Assessing Marijuana Promotions on Social Media: Theory, Health Information and Youth Targeting

Megan A. Moreno, MD, MSEd, MPH, Associate Professor
Pediatrics

Description: Adolescents are an important at-risk population for marijuana given the high prevalence of use and the negative health consequences for this age group. The legalization of adult recreational marijuana use in Washington State will affect underage adolescents despite legal limitations on their ability to purchase marijuana in stores. Adolescents are now exposed to recreational marijuana promotions through social media such as Facebook and Twitter. Teens are consistently among the most ubiquitous and frequent users of social media. Marijuana businesses can create publicly available “business pages” on social media to promote products and engage with customers interactively. Decades of research on tobacco and alcohol illustrate that marketing contributes to positive intentions and initiation of use for these substances. However, marijuana promotions present new approaches and challenges that must be understood to inform effective prevention strategies and policies. Now is a critical time to understand marijuana promotions while policies that regulate them are nascent or in development.

The objective of this study is to fill essential gaps in knowledge to understand the content and strategy of recreational marijuana promotions. Aim 1 will include content analysis of marijuana promotions on social media, assessing one year of content for 12 businesses on Facebook and Twitter. We will apply the Facebook Influence Model, assess health claims and determine prevalence of youth targeting. Aim 2 will include perspectives of youth on marijuana social media promotions including a validation of our coding approach by youth. We will utilize findings towards informing policies regarding marijuana promotions and future educational interventions targeting adolescents.

Resulting articles & projects:

  • The pilot work in this project formed the basis for a funded NIDA grant to Dr. Moreno: "Marijuana Ads in Traditional and Social media: Influences and Policy Implications." (R01DA041641-01A1). Details in NIH Reporter

2016 October I-171 Funds

Cannabidiol Rescue of Autism Behavior and Cognitive Impairment from Scn1a Genetic Mutation

Joshua Kaplan, Ph.D, Postdoctoral Fellow
Pharmacology

William A. Catterall, Ph.D., Pharmacology

Description: Dravet Syndrome (DS) is a severe childhood neuropsychiatric disorder characterized by treatmentresistant epilepsy, cognitive impairment, and autism. Unfortunately, traditional anti-epileptics are ineffective at reducing seizures in DS. Our lab developed a genetic mouse model of DS which is an exact phenocopy of the human condition, thus making it an optimal precision medicine tool for testing the efficacy of novel pharmacological strategies in treating not only seizures in DS, but other aspects of the disorder as well. In preliminary experiments, acute administration of cannabidiol (CBD, a nonpsychoactive constituent of the cannabis plant) reduced seizure in our mouse model of DS. These results are corroborated by anecdotal reports and an open-label clinical trial suggesting that CBD reduces seizures in DS. While these results are encouraging, the impacts of CBD on cognitive impairment and autistic behavior in DS, and the cellular mechanisms that mediate this therapeutic effect, have yet to be determined.

The two aims of this proposal are designed to establish the therapeutic efficacy and physiological mechanism of acute and chronic CBD administration on cognitive impairment and social deficits in our mouse model of DS. The first aim will determine if a single acute dose or chronic (3x/day for 2 weeks) CBD rescues cognitive impairment in spatial and contextdependent memory tasks, and autistic-like behavior using sociability tests in which DS mice show profound impairment. The second aim will use slice-electrophysiology to determine the molecular mechanism that mediates chronic CBD’s impact on excitatory and inhibitory transmission in the dentate gyrus, a key brain area involved in the generation of seizures.

These experiments will help build a strong foundation for the development of targeted pharmacological strategies for the treatment of all aspects of DS, as well as help guide medicinal treatment strategies for using cannabis and its derivatives in treating DS.

Resulting articles & projects:

  • Kaplan JS, Stella N, Catterall WA, Westenbroek RE. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc Natl Acad Sci U S A. 2017 Oct 2. pii: 201711351. doi: 10.1073/pnas.1711351114. Pubmed abstract.

Racial/Ethnic and Rural Differences in Prevalence of Alcohol Use, Care, and Related Outcomes among VA Patients Living with HIV

Kara Bensley, M.Sc., Ph.D. Student
Health Services

Emily Williams, Ph.D., M.P.H., Associate Professor, Health Services (Mentor)

Description: Alcohol use is associated with poor HIV-related outcomes and affects racial/ethnic minorities and people living in rural areas. However, whether alcohol use, receipt of alcohol-related care, and associations between alcohol use and HIV-related outcomes vary across vulnerable subpopulations of PLWH is unclear.

SPECIFIC AIMS: Among PLWH, we will investigate: 1) whether the association between severity of alcohol use and mortality varies by race/ethnicity, 2) whether patterns of alcohol use vary based on rurality, and 3) whether receipt of evidence-based alcohol-related care varies across race/ethnicity and rurality among PLWH with unhealthy alcohol use.

APPROACH: National VA data from the Veterans Aging Cohort study will be used to identify all PLWH who received care in the VA and had a documented AUDIT-C screen (2008-2014). For Aim 1, cox proportional hazard ratios will be used to evaluate whether race/ethnicity modifies the association between alcohol use and mortality. In Aim 2, we will describe patterns of alcohol use across rural status and region and assess the association between rurality and patterns of alcohol use using mixed effect regression models. In Aim 3, we will describe receipt of alcohol-related care across race/ethnicity and rural status using poisson regression models clustered on the patient. Analyses in all three aims will be adjusted for demographic characteristics; Aim 1 will be additionally adjusted for HIV disease severity and comorbidities.

IMPACT: This research uses the largest dataset of PLWH in care in the U.S. to better understand whether some subpopulations of PLWH have increased prevalence of alcohol use and/or are more susceptible to adverse alcohol-related consequences, as well as whether subpopulations have decreased access to alcoholrelated care. This research will provide an important foundation for developing more targeted interventions among subpopulations of PLWH at particularly high risk of poor alcohol-related outcomes.

Investigation of Sexual Victimization Severity and Pre-Sex Drinking: The Roles of Sex-Related Stress and Sex-Related Drinking Motives

Elizabeth R. Bird, MS, Graduate Student
Psychology

William H. George, Ph.D., Professor, Psychology (Mentor)

Description: Women ages 18-24 are at the highest risk for sexual victimization (SV), with more than 20% of women affected during their college years. The period of highest risk is the first year of college. Psychological distress and alcohol use both increase following SV and women endorse drinking as a behavior to cope with psychological distress following SV, referred to here as a general drinking motive. Women with a history of SV engage more frequently in pre-sex drinking–drinking before or during sexual activity, compared to women without an SV history. While pre-sex drinking is associated with sexual risk-taking and revictimization, pathways through which this risky drinking behavior occurs have received limited attention. Sexual health variables such as sex-related distress (i.e. distress related to sexual behavior or sexuality) and sex-related drinking motives such as drinking to cope with sex-related distress may mediate the relationship between SV and pre-sex drinking, representing a unique and self-perpetuating pathway to recurrent risky drinking behavior.

The current study examines the relationships among SV, sex-related distress, sex-related drinking motives, and pre-sex drinking in first year college women (N = 380). The primary objective is to understand if sex-related factors – distress and motives – are associated with pre-sex drinking controlling for variables not specifically associated with sexuality: psychological distress, general drinking motives, and typical drinking. Data will be gathered online three times over a three-month period (baseline, 6 weeks, and 12 weeks), collected through the University of Washington Psychology Subject Pool.

Given the unique risks to physical and mental health posed by risky drinking and risky sexual behaviors, clarifying the relationship between SV and pre-sex drinking might enhance addiction science, and amplify the effect of interventions targeting college students.

Effects of Cannabinoids on Endometrial and Trophoblast Cell Growth and Differentiation

Naveen Neradugomma, PhD, Senior Research Fellow
Pharmaceutics

Qingchen Mao, Pd.D., Associate Professor, Pharaceutics (Mentor)

Description: Marijuana is the most exploited substance of abuse. Recent laws legalizing recreational marijuana may result in greater marijuana use during pregnancy, particularly among the socioeconomically disadvantaged pregnant women in the US. New legislations generate a greater urgency to investigate the role of cannabinoids in pregnancy. NIH and American College of Obstetricians and Gynecologists (ACOG) acknowledge the insufficient data related to the effects of marijuana on pregnancy and proposed the need for more research.

Marijuana was historically used as an analgesic. Absorbed through lungs and/or gastrointestinal tract, it is mainly metabolized in the liver. Delta-9-tetrahydrocannabinol ( 9-THC), cannabidiol (CBD) and cannabinol (CBN) are the active components of marijuana, with 9-THC and CBD being the most psychoactive components. Cannabinoids activate cannabinoid receptors CB1, CB2 and GPR55, to influence diverse physiological activities. In-utero exposure to cannabinoids disrupts fetal brain development and function in rodents. Human studies suggest that marijuana use leads to anencephaly, lower birth weight, placental abruption, preterm birth and spontaneous miscarriage. However, data on mechanistic understanding of the adverse effects of cannabinoids on pregnancy outcomes is scarce.

We propose to investigate the effects of cannabinoids on endometrial and placental cells in vitro, using transformed and primary cells. We hypothesize that cannabinoid compromise endometrial differentiation and placental development. Our specific aims are Aim 1: 1a) Investigate whether cannabinoids (THC, CBD and CBN) interfere with growth and decidualization (differentiation) of endometrial cells using an immortalized human endometrial stromal cell line; 1b) Determine if the effects are mediated by cannabinoid receptors and determine the cannabinoid receptors involved. Aim2: 2a) Investigate whether cannabinoids (THC, CBD and CBN) interfere with growth and syncytialization (differentiation) of placental cells using the model human placental BeWo cell line and primary human trophoblasts; 2b) Determine if the effects are mediated by cannabinoid receptors and determine the cannabinoid receptors involved.

Pilot Study of Video-Based Directly Observed Therapy (vDOT) for Office-Based Treatment of Opioid Use Disorders with Buprenorphine

Judith Tsui, M.D., M.P.H., Associate Professor
Internal Medicine

Description: There is an epidemic of opioid use disorders (OUD) in the U.S., and as a result, there is a critical need for expanded treatment of these disorders. Medication assisted treatment (MAT) of OUD with buprenorphine in office-based settings has been shown to be effective. Yet retention rates are low, with up to half of patients relapsing to opiate use and dropping out within 12 months. There is a strong need to develop interventions to support patient adherence to treatment.

We propose to use this grant to fund a pilot study of Video-Based Directly Observed Therapy for Office-Based Treatment of Opioid Use Disorders with Buprenorphine. This will be the initial step to develop a sustainable, scalable, and patient-centered mobile health (mHealth) platform, comprised of a patient-facing mobile application and provider-facing web portal, for OUD treatment. Directly observed therapy (DOT) is highly effective in securing medication ingestion but is costly, labor-intensive, and logistically challenging. Methadone clinics have used DOT for treatment for decades, but there are not enough methadone clinics to support the care needs of over 2 million patients with OUD. Office-based buprenorphine programs can expand access to care for this population but face similar capacity constraints with providing the frequent care needed for this population during initial months of treatment. Also, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication.

This proposal will pilot a video-based directly observed therapy application for office-based buprenorphine monitoring that can be used during the initial months of care, or later when patients are struggling with relapse. The study will customize an existing asynchronous, video-based mobile application (miDOT) and provider web portal to confirm medication ingestion and provide digital support and patient engagement tools, including HIPAA-secure in-app chat, cravings reporting, and appointment reminders.