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2006 March

The Effects of Thought Suppression vs. Acceptance-Based Strategies on Smoking Following Cue Exposure

Sarah Bowen
Predoctoral Research Associate Trainee

Psychology

G. Alan Marlatt, PhD
Professor, Department of Psychology
Director, Addictive Behaviors Research Center

Description: Rates of tobacco use are alarmingly high, and harm attributable to use, in health, lives and dollars, is substantial. Although smoking is the leading preventable cause of death in the U.S., 70% of those receiving smoking cessation treatments are likely to resume smoking within the first year. Avoidant cognitive strategies, such as will power and distraction techniques, are often employed in cessation attempts. However, these techniques are not supported by the literature. In fact, they often show iatrogenic effects. Thought suppression techniques have, in several studies, increased the frequency of unwanted thoughts. Thus, for those attempting to suppress cravings or thoughts about smoking, this is a potentially problematic technique. There are few studies examining effects of mindfulness or acceptance-based strategies in substance use treatment. The small extant body of literature suggests that acceptance-based strategies can help increase tolerance to uncomfortable physical states (e.g., craving) and subsequently reduce use of substances.

The overarching goal of our proposed research is to assess influences of thought suppression vs. acceptance-based techniques on cravings, affect, intention and behaviors in nicotine-deprived adult smokers following a cue exposure. Additionally, we wish to identify mediating and moderating roles in the relationship between these strategies and smoking outcomes.

Resulting articles & projects:

  • Bowen S, Marlatt GA. Surfing the urge: Brief mindfulness-based intervention for college student smokers. Psychol Addict Behav 2009;23(4):666-671 [PubMed abstract ]
  • Bowen, S. & Marlatt, G. A. (2007) Effects of Mindfulness-Based Strategies on Urges, Negative Affect and Smoking. Presented at the Association for Cognitive and Behavior Therapy 41st Annual Conference, Philadelphia, PA.
  • Owens, M., Douglass, A. & Bowen, S. (2008). Coping with Craving: Strategies Smokers. Poster presented at the 88th annual conference of the Western Psychological Association, Irvine, CA.

Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone in Human Subjects

Rheem A. Totah, PhD
Acting Assistant Professor

Medicinal Chemistry

Description: Methadone maintenance treatment (MMT) has been used to rehabilitate the opiate addict, resulting in a higher quality of life for the patient as well as improving social and psychological functioning while reducing the overall cost to society. The maintenance dose of methadone is highly variable among patients and drug-drug interactions have been observed between methadone and various medications used to treat a variety of diseases. Identification and understanding of the enzymes responsible for the metabolism of methadone could potentially lead to improved strategy in individualizing methadone dosing and reduce the risks of adverse drug interactions.

Several cytochrome P450 enzymes (CYPs) have been identified and hypothesized to be involved in methadone metabolism in vitro, particularly CYP2B6 and CYP3A4. However, the quantitative contribution of CYP2B6 and CYP3A4 in the elimination clearance of methadone in vivo remains undefined. In addition, methadone is a substrate of the efflux transporter-P-glycoprotein (Pgp) at the intestinal mucosa.

We are proposing a pilot study in healthy human subjects to investigate the following hypotheses: 1) Pgp limits the gastrointestinal absorption, and 2) inter-subject variations in CYP2B6 and CYP3A4 activities explain the variation in methadone clearance in vivo. This will be accomplished by correlating the pharmacokinetics of methadone and the phenotype probes for Pgp (digoxin), CYP2B6 (bupropion) and CYP3A4 (midazolam). We plan to use these data to design a human subject study to assess the utility of MDR1 and CYP genotyping in predicting the methadone maintenance dose in a cohort of MMT patients.

2006 October

Gestational Cocaine Exposure Mediates Long-Term Changes in Striatal Function

Nigel S. Bamford, MD
Assistant Professor

Neurobiology, Pediatrics

Description: The objective of this proposal is to develop an animal model of gestational cocaine exposure and determine the behavioral and physiological effects of maternal psychostimulant abuse on the developing striatum,. Evidence suggests that prenatal cocaine exposure results in impairments of cognition and motor function in children. We hypothesize that exposure to cocaine in utero results in enduring striatal neuroadaptations that are manifest by developmental and behavioral abnormalities in affected mice. Our preliminary data demonstrates that dopamine released by psychostimulants acts to filter cortical information by inhibiting excitatory signals with a low probability of release. In this way, dopamine boosts stronger connections while inhibiting weaker signals. In adult and neonatal mice, chronic psychostimulant exposure disrupts striatal filtering by inducing a long-lasting depression of glutamate release. Drug reinstatement partially reverses this depression, an effect that is dependent on both dopamine and acetylcholine. By developing an animal model for gestational cocaine exposure, our proposed study seeks to determine how exposure to cocaine in utero affects physiological development in weanling and adolescent mice. Behavioral investigations will determine if prenatal cocaine exposure induces long-lasting changes in locomotor behavior and sensitized responses to a drug challenge. Finally, electrophysiological recordings will determine if these behavioral changes are accompanied by alterations in corticostriatal release. This project will provide an animal model with which to investigate the physiological mechanisms underlying abnormal behaviors in drug exposed animals and will provide insights into pharmacological alternatives for improved treatment of infants born to drug-addicted mothers. These data will provide the necessary groundwork for NIH funded investigations into the mechanisms of toxicology and addiction.

Resulting articles & projects:

  • Wang W, Nitulescu I, Lewis JS, Lemos JC, Bamford IJ, Posielski NM, Storey GS, Phillips PEM, Bamford NS. Overinhibition of corticostriatal activity following prenatal cocaine exposure. Ann Neurology 2012 (Nov 9 ahead of print). doi: 10.1002/ana.23805. [PubMed abstract ]
  • Nitulescu I, Rao M, Scarlis CA, Bamford NS. Behavioral and Neuroplastic Changes Due to Gestational Cocaine Exposure. Poster presented at the 2009 Neurobiology & Behavior meeting.
  • Poster presented at the 135th meeting of the American Neurological Association, San Francisco, 2010.
  • Ludwick L, Scarlis C, Lowe J, Towne J, Bamford NS. (2008) Gestational Cocaine Exposure Produces Age-Dependent Alterations in Locomotor Activity. 11th Annual UW Undergraduate Research Symposium, p65.
  • Nitulescu I, Rao M, Scarlis CA, Bamford NS. October, 2009. UW-HHMI Biology Undergraduate Research Symposium

Treatment of Stimulant Dependence in HIV Infected Patients with Price-Based Contingency Management

W.R. Murray Bennett, MD
Assistant Professor

Psychiatry & Behavioral Sciences

Description: Successful treatment of HIV infection has major public health significance but requires management of problems outside of the infections itself that impact treatment adherence and health outcomes. Of particular importance among these problems is substance use, especially stimulant use. Stimulant use is associated with both negative health outcomes and risky behaviors that are linked with the spread of HIV. We therefore propose a pilot study to evaluate the feasibility, acceptability, and efficacy of using contingency management to decrease stimulant use and increase engagement with routine medical care among HIV-positive patients at Harborview's Madison Clinic. 33 subjects with current stimulant use will be recruited from the Madison Clinic and randomized either to 12 weeks of contingency management (CM) -- in which rewards will be given for clean drug tests and engagement with treatment -- or 12 weeks of treatment-as-usual. Feasibility and acceptability will be measured by comparative engagement and retention of participants in the treatment (CM) versus control (TAU) program. Efficacy in terms of stimulant use will be assessed as a function of the difference beaten CM and TAU conditions in stimulant use as measured by urine toxicology testing, number of days of abstinence from stimulant use and change in addiction severity as documented by the Addiction Severity Index. Efficacy in terms of engagement with treatment will be measured by number of medical, case management, and other appointments attended as part of routine clinical care. It this pilot provides promising results it will serve as a demonstration project for a larger grant project to develop a low-cost stimulant treatment and medical engagement program for HIV clinics.

Resulting articles & projects:

  • Because the final data analyses are not complete, we have not yet submitted them for presentations or presentations.
  • We have not secured other funds but are considering a number of NIH requests for applications and program announcements.
  • Our work took place at the Madison Clinic at HMC, which is an established research facility. That said, this was the first randomized controlled trial of a behavioral intervention conducted by Psychiatry and Behavioral Sciences faculty at the Madison Clinic. Lessons learned during the process will undoubtedly benefit future efforts.

Examining Genetic Polymorphisms in Relation to Alcohol Expectancies and Drinking in Asian Americans

Christian Hendershot, PhC
Doctoral Student

Psychology

William H. George, PhD (Mentor)
Professor and Director, Institute for Ethnic Studies, Department of Psychology

Description: Recent evidence suggests increasing rates of heavy drinking and alcohol use disorders among Asian Americans. Genetic variations in alcohol metabolizing enzymes are demonstrated to influence alcohol sensitivity and drinking behavior in this group,. however few studies have examined genetic factors in the context of psychosocial theories of alcohol use. This study will incorporate alcohol expectancies as a conceptual framework for examining joint influences of genetic and psychosocial factors on drinking behavior in Asian groups.

180 Chinese and Korean Americans will be recruited from an ongoing prospective study of college student drinking at the University of Washington. At baseline assessment, participants will complete questionnaires assessing alcohol use and expectancies, and will provide a blood sample for genotyping. Polymorphisms at four loci implicated in alcohol use behavior -- ALDH2, ALDH1A1, ADH1B, and ADH1C -- will be assessed. At 6 and12 months post-baseline, participants will log on to a secure website and complete questionnaires reassessing alcohol use and expectancies. Prospective data will allow for examination of mediating relationships among genetic factors, expectancies, and drinking. The influence of ethnicity, gender, acculturation, and other psychosocial factors will also be examined. By jointly studying genetic and psychosocial factors, this research aims to further a biospsychosocial account of alcohol use etiology in Asian Americans. Identification of ethnic group-specific etiologic factors may inform the development of culturally tailored prevention and intervention programs.

Resulting articles & projects:

  • Dr. Hendershot received an F32 training grant for 2009-2011 from NIAAA: "Alcohol and HIV Risk: Genetic and Endophenotype Approaches" (Total direct costs: $104,565) F32AA018629
  • Hendershot CS, Neighbors C, George WH, McCarthy DM, Wall TL, Liang T, Larimer ME. ALDH2, ADH1B and alcohol expectancies: Integrating genetic and learning perspectives. Psychol Addict Behav 2009;23(3):452-463. [PubMed abstract | Free in PubMed Central]
  • Hendershot CS, Lindgren KP, Liang T, Hutchison KE. COMT and ALDH2 polymorphisms moderate associations of implicit drinking motives with alcohol use. Addiction Biology (2011 in press).
  • Hendershot CS, Witkiewitz K, George WH, Wall TL, Otto JM, Liang T, Larimer ME Evaluating a cognitive model of ALDH2 and drinking behavior. Alcoholism: Clinical & Experimental Research (2011 in press).
  • Hendershot CS, Otto JM, Collins SE, Liang T, Wall TL Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2. Annals Behav Med 2010;40(1):77-88. [PubMed abstract]
  • Hendershot CS, Collins SE, George WH, Wall TL, McCarthy DM, Liang T, Larimer ME. Associations of ALDH2 and ADH1B genotypes with alcohol-related phenotypes in Asian young adults. Alcohol Clin Exper Res 2009;33(5):839-847. [PubMed abstract | Free online]
  • Lindgren KP, Hendershot CS, Neighbors C, Blayney JA, Otto JM. Implicit alcohol motives predict unique variance in drinking in Asian-American college students. (Manuscript under review)
  • Hendershot CS, Lindgren KP, Liang T, Hutchison KE Interactive effects of COMT Val158Met and automatic alcohol cognitions on drinking behavior. Presented at the Annual Meeting of the Research Society on Alcoholism, San Antonio, TX, June 2010.
  • Hendershot CS, Collins SE, Otto JM, Wall TL, Liang T A brief web-based feedback intervention for reducing alcohol-related health risks associated with ALDH2 genotype. Paper presented at the Annual Meeting of the Research Society on Alcoholism, San Antonio, TX, June 2010.
  • Lindgren KP, Hendershot CS, Blayney JA. Automatic alcohol-related cognitions predict unique variance in weekly drinking and heavy drinking episodes in an Asian-American college sample. Presented at the Annual Meeting of the Research Society on Alcoholism, San Antonio, TX, June 2010.
  • Hendershot CS, Collins SE, Otto JM, Wall TL, Liang T. Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2*2. Paper presented at the Society of Behavioral Medicine Annual Meeting and Scientific Sessions, Seattle, WA, April 2009.
  • Hong NV, Hendershot CS. Culture, alcohol use and sexual risk in Korean and Chinese Americans. Paper presented at the Society of Behavioral Medicine Annual Meeting and Scientific Sessions, Seattle, WA, April 2009.
  • Hendershot CS, Witkiewitz K, George WH, Wall TL, Liang T, Larimer ME. Effects of ALDH2 genotype on alcohol use are mediated by drinking motives. Paper presented at the Annual Meeting of the Research Society on Alcoholism, San Diego, CA, June 2009.
  • Hendershot CS, Lindgren KP, Otto JM, Blayney JA, Hur E, Dang K, Liang T A genetic association with automatic alcohol cognitions: ALDH2 and automatic drinking motives. Presented at the Annual Meeting of the Research Society on Alcoholism, San Diego, CA, June 2009.
  • Hendershot CS, Neighbors C, George WH, McCarthy DM, Wall TL, Liang T, Larimer ME. Associations of ALDH2 and ADH1B genotypes with alcohol expectancies and drinking behavior. Presented at the Annual Meeting of the Research Society on Alcoholism, San Diego, CA, June 2009.
  • Lindgren KP, Hendershot CS, DiBello A, Henry S, Blayney JA. Automatic alcohol related cognitions predict alcohol consumption and alcohol-related problems in an Asian-American college sample. Presented at the Annual Meeting of the Research Society on Alcoholism, San Diego, CA, June 2009.
  • Dang K, Hendershot CS, George WH. Examining ethnicity, acculturation and loss of face as correlates of drinking behavior in Asian Americans. Poster presented at the University of Washington 12th annual Undergraduate Research Symposium, May 2009 (mentored research project).
  • Hendershot CS. ALDH2 and alcohol use in Asian Americans: Alcohol expectancies as an intermediate phenotype. Paper presented at the 6th Annual NIAAA Trainee Workshop, Research Teams of the Future: Diversity, Interdisciplinary, Translational. New Orleans, LA, March 2009.
  • Otto J, Hendershot CS, George WH Association of the ALDH1A1*2 polymorphism with alcohol expectancies and drinking behavior in Asians. Poster presented at the University of Washington 11th annual Undergraduate Research Symposium, May 2008 (mentored research project).

Beyond BASICS: Enhancing Interventions for College Students Drinking to Cope

Ursula Whiteside, MS
NIAAA Predoctoral Research Fellow
Doctoral Candidate

Psychology

Mary Larimer, PhD(Mentor)
Associate Professor, Psychiatry & Behavioral Sciences

Description: College student drinkers have been suggested to fall into two broadly defined categories: sensation-seeking social drinkers, and emotion-coping drinkers. The second and smaller group experiences more psychological difficulties and may carry greater risk of alcohol chronicity. Interventions targeting the specific problems of this group are largely unavailable on college campuses and are sorely needed for this critical subset of drinkers.

The goals of this proposed 2-phase research project are to establish, manualize, and pilot test an intervention for emotion coping drinkers. These phases are in correspondence with phases 1a and 1b of State 1 of the State Model of Behavioral Therapies Research. For Phase 1, we plan to develop a treatment manual adapted from the established Brief Alcohol Screening and Intervention for College Students (BASICS). This adapted version will target college students drinking primarily for coping reasons and will integrate an emotion regulation theory of behavior while incorporating several key coping skills (i.e. mindfulness with opposite action and problem solving) taught in the group component of Dialectical Behavioral therapy (DBT). For Phase 2, we plan to pilot-test the adapted version (DBT-BASICS) in order to evaluate its effectiveness in comparison to BASICS and treatment as usual (TAU). Students for Phase 1 and Phase 2 will be screened and recruited using questionnaires administered via mass testing sessions conducted through he Psychology Human Subject Pool. It is expected that 9% of the screening sample will meet study criteria and of those, 70% will consent to study participation. In order to meet study sample goals, we will screen approximately 650 students during Phase 1 and 1800 during Phase 2 to yield 40 and 114 participants respectively. Screening will occur across 3 quarters (Phase 1 across 1 quarter and Phase 2 across 2 quarters) and follow-up assessments will occur at 4-weeks and 3-months.

Resulting articles & projects:

  • This ADAI grant was instrumental in the successful application for an individual NRSA grant from NIAAA for "Adapting Interventions for College Student Drinkers," 5F31AA016038-02
  • Dr. Whiteside also received an APA Division 12 dissertation grant to continue this research and complete her dissertation.