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2015 October I-502 Funds

Characterizing Cannabis Use in Veterans with Posttraumatic Stress Disorder

Kendall Browne, Ph.D.
Acting Instructor/Senior Fellow

Psychiatry & Behavioral Sciences

Co-Investigators: Andrew Saxon, M.D., Professor, Psychiatry & Behavioral Sciences; Tracy Simpson, Ph.D.,Associate Professor, Psychiatry & Behavioral Sciences; Marcel Bonn-Miller, Ph.D., Research Health Science Specialist, VA Palo Alto Health Care System; Lauren Pomerantz Augello, M.D, Psychiatry Resident, Psychiatry & Behavioral Sciences; Marketa Krenek, Postdoctoral Fellow, VA Puget Sound Health Care System

Description: Rates of cannabis use, misuse and cannabis use disorders (CUD) are high among individuals with posttraumatic stress disorder (PTSD). Over twenty states have legalized cannabis for medicinal use, including nine states that list PTSD as an approved condition. Four states have legalized the sale of cannabis for recreational use. Thus, cannabis misuse may become even more prevalent within this vulnerable population as access increases and legal consequences are removed. Empirical studies have contributed to our early understanding of the cross-sectional relations between PTSD symptom severity and cannabis use, however, this work has lacked the methodological rigor required to draw meaningful conclusions regarding the potential bi-directional relations between PTSD, cannabis use, and related variables (e.g., motives to use, craving). Developing a greater understanding of how, what, and why individuals with PTSD choose to use cannabis and how this use interacts with PTSD symptoms will be essential to the development of appropriate services for individuals with PTSD who use cannabis.

The objective of this study is to build our understanding of cannabis use in individuals with PTSD by: 1) characterizing cannabis use patterns and motives in individuals with PTSD symptoms, 2) conducting the first prospective examination of the day-to-day relations between PTSD and cannabis use, and 3) conducting the first effort to qualitatively describe the perspective of patients with PTSD who use cannabis. To achieve this objective the research group will utilize a mixed methods approach incorporating an online survey (n = 200), daily symptom and use monitoring (i.e., interactive voice response; n = 48), and in-depth qualitative interviews (n = 30) with Veterans enrolled in PTSD treatment who report at least weekly cannabis use. These data will provide an essential foundation on which to build a range of future research efforts along with educational, assessment, and intervention resources.

Resulting articles & projects:

  • This project attracted additional grant funding from the Veterans Affairs VA Puget Sound Health Care System Research & Development Small Grant Program, which will allow expansion to include VA San Diego. Data from the expanded study will provide an essential foundation for future research efforts and educational, assessment, and intervention resources by helping to develop objective, quantitative measures that will enhance future grant proposals.

Steps Toward a Nation-wide Examination of the Effect of Marijuana-related Legislation on Adolescent Substance Use and Related Risk Factors

Katarina Guttmannova, Ph.D.
Research Scientist

Social Development Research Group

Charles B. Fleming, M.A. (Co-Investigator)
Research Scientist
Social Development Research Group

Description: A wave of changes in marijuana laws has swept across U.S. states in recent years. Almost half of states now allow for medical marijuana, and four states (Washington, Colorado, Oregon, and Alaska), as well as the District of Columbia, have also legalized recreational marijuana. The shifting legal climate with respect to marijuana could potentially lead to increased availability of marijuana for adolescents, as well as more favorable community and parent attitudes towards marijuana use. This could, in turn, result in increased use of marijuana and other drugs among adolescents, which would have important public health consequences. Understanding the effects of law changes is imperative for guiding public policy and crafting and implementing laws that minimize the harms of adolescent marijuana use.

This study builds on and extends to new territories the current NIDA-funded R21 project that evaluates cannabis-related policies in five states. Investigators gathered and harmonized data on marijuana and other substance use and marijuana-related risk factors from an additional 18 states that have medical or recreational legislations and develop detailed state-specific marijuana policy timelines for these states. This work will be the foundation for further extramural funding and a nationwide examination of the impact of state-level marijuana legislation – including Washington State’s I-502 – on marijuana-related risk factors and substance use outcomes among youth.

Resulting articles & projects:

  • Cambron C, Guttmannova K, Fleming CB. State and National Contexts in Evaluating Cannabis Laws: A Case Study of Washington State. J Drug Issues 2017;47(1):74–90. DOI: 10.1177/0022042616678607. PMID: 28458396; PMCID: PMC5404705
  • The data and timelines from this project were incorporated into an NIH/NIDA R01 grant application (R01DA043483; title: The Impact of State Variation in Marijuana Laws on Adolescent Substance Use, Related Risk Factors and Consequences). Dr. Guttmannova is the PI of this R01 and Mr. Fleming is one of the co-investigators. The grant application was submitted in June 2016; revised for the February 2017 review cycle but not funded, and will be revised and submitted again in February 2018.
  • Timelines for states' adoption of laws and regulation of recreational and medical marijuana developed for this project are available on the website in the Policy and Law section.

Development of a Novel and Translational Model of Binge Ethanol and Tetrahydrocannabinol Intake in Adolescent Rats

Lauren C. Kruse, Ph.D.
Postdoctoral Fellow

Psychiatry & Behavioral Sciences

Jeremy J. Clark, Ph.D. (mentor)
Assistant Professor
Psychiatry & Behavioral Sciences

Description: Alcohol and marijuana are the most commonly used drugs among adolescents and are often used in combination. Initial experimentation with alcohol and marijuana typically occurs early in life and age of first use is predictive of abuse or dependence of one or both of these substances later in life. Drug exposure during adolescence is thought to alter normal brain development producing long-term neurobiological and behavioral changes that may underlie increased risk for chronic alcohol abuse problems in adulthood, but less is known about the long-term consequences of combined alcohol and marijuana use. Adolescents frequently consume alcohol in a highly dangerous pattern of intake known as heavy episodic or binge drinking that produces substantial behavioral intoxication and pharmacologically relevant blood alcohol levels in a short period of time.

A recurring issue in preclinical research is the availability of rodent models of oral drug self-administration that produce significant levels of intake and effectively model the human condition. Particularly, this absence of relevant models has proven to be a hindrance in the neurobiological examination of alcohol dependence after adolescent binge drinking and in the development of effective preventative and treatment strategies. Further, animal models of polydrug self-administration (e.g., alcohol and marijuana) are missing. For these reasons, the development of a rodent model of binge alcohol intake and concurrent marijuana use that closely models the human condition is crucial for advancing our understanding of the role of early-life drug use in the pathology of alcohol use disorders.

The proposed work seeks to establish and validate a translational model of adolescent binge ethanol intake, and to develop a novel model of polydrug self-administration, with the long-term goal of expanding our current understanding of the neurobiological and behavioral consequences of this harmful pattern of intake on learning and decisionmaking systems as a potential basis for addiction.

Resulting articles & projects:

  • The findings will be used as preliminary data in the submission of a collaborative R01 grant between Drs. Jeremy Clark and Nephi Stella. The proposed R01 will explore the long-term consequences of adolescent THC use on reward neurocircuitry and decision-making in adulthood.
  • Kruse LC, Cao J, Stella N, & Clark JJ. A novel model of tetrahydrocannabinol self-administration in adolescent rats. (Manuscript in preparation)

Marijuana Use and Disorders from Adolescence into Young Adulthood: Examining Descriptive Epidemiology and Mental Health Risk Factors in a Community-based Prospective Cohort

Isaac C. Rhew, Ph.D., MPH
Research Assistant Professor

Psychiatry & Behavioral Sciences

Ann Vander Stoep, PhD (Co-Investigator)
Associate Professor, Department of Psychiatry & Behavioral Sciences, Department of Epidemiology; Adjunct, Department of Global Health

Description: For this study, we will conduct secondary data analyses (SDA) on eight waves of longitudinal data from the Developmental Pathways Project (DPP). The first study aim is to document the descriptive epidemiology and developmental trajectories of marijuana use and disorders over the developmental period from early adolescence through young adulthood. The second aim is to use marginal structural modeling to elucidate the role of depression and conduct problems in the etiology of marijuana use and disorders.

With ADAI small grant funding we will prepare longitudinal data, conduct analyses, and write up results to invest as preliminary studies in an R-01 to be submitted to NIDA in June 2016. The aims of the R-01 SDA proposal will be to address pressing questions about the phenomenology, etiology, and consequences of marijuana use and disorders across the developmental period from early adolescence to young adulthood, to understand differences and similarities in developmental patterns of marijuana and alcohol use and disorders, and to evaluate the effects of marijuana policy changes on young adult marijuana use, perceived norms and harms, and motives.

Resulting articles & projects:

  • Preliminary data from this ADAI project were incorporated into an NIH/NIDA R01 grant application (R01DA043498-01). Dr. Rhew is the PI of this R01; Dr. Ann Vander Stoep (co-investigator on this ADAI project) and Mr. Fleming are among the co-investigators. The title of this grant is “Coming of age in the context of legalization: Problematic marijuana use and its emotional health and functional antecedents and consequences in adolescents and young adults in Washington State.” Submittted in June 2016 but not funded; to be resubmitted October 2017.
  • Rhew IC, Fleming CB, Vender Stoep A, Nicodimos S, Zheng C, McCauley E. Examination of cumulative effects of early adolescent depression on cannabis and alcohol use disorder in late adolescence in a community-based cohort. Addiction. 2017 Jun 10. doi: 10.1111/add.13907. [Epub ahead of print] PubMed Abstract PMID: 28600897.
  • Rhew IC, Fleming CB, Zheng C, Vander Stoep A, McCauley E. Cumulative effects of early adolescent depression on marijuana and alcohol use disorder in late adolescence in a community-based cohort. Paper presented at the 50th Annual Meeting of the Society for Epidemiologic Research. Seattle, WA. June 21, 2017

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

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

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

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