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2007 March

Neurocognitive Side Effects and Pharmacodynamics of Methadone in Older Adults

Monique Cherrier, PhD
Research Associate Professor

Psychiatry & Behavioral Sciences

Dr. Danny Shen (UW-Pharmacy), Dr. Andrew Saxon (VA, CESATE), Dr. Tracy Simpson (VA, CESATE)

Description: The number of older adults in need of substance abuse treatment is estimated to increase from 1.7 million in 2000 to 4.4. million 2020. This increase in the number of individuals in need of substance abuse treatment is due to an expected 50% increase in the number older adults in the near future and a 70% increase in the rate of treatment needed in that cohort (1). Methadone is a commonly used substitution therapy in heroin and other opioid substance abusers. The rate of prescriptions for methadone has steadily increased in the past ten years not only for methadone substitution therapy but also for chronic pain (2). Persistent pain, sufficient to cause significant impairment in daily functioning, affects up to 50 percent of older adults (3). Analgesics are the most common therapy used to manage pain (3), with methadone increasingly being noted have advantages in the treatment of chronic disabling pain in older adults, with one significant advantage being cost savings (4, 5). Despite an increase in use, to date, no studies have examined the pharmacokinetics, side effects or neurocognitive effects in older adults. The efficacy of medication therapy needs to be balanced against potential side effects, including the risk of neurocognitive impairment. However, to date, no studies have examined or characterized the neurocognitive effects of methadone in older adults. The proposed study will measure the objective and subjective neurocognitive effects of methadone in healthy older (>65 years) adults at a specified dose. We will also characterize the pharmacokinetics and pharmacodymanics (pk-pd) and potential for balance and nocturnal breathing changes. We expect that healthy older adults will demonstrate greater decrements in attention, memory and balance as well as more significant changes in nocturnal breathing at the time of peak drug response compared to baseline. Further, Intersubject variability in peak neurocognitive response and will be explained, in part, by variation in peak plasma concentration of methadone.

This study addresses the recent FDA Public Health Advisory on the use of methadone for pain control. This project represents a novel idea of inquiry because to date there have been no rigorously controlled studies of the pk-pd or neurocognitive effects of methadone in older adults. The present study conducted in healthy, pain-naïve and drug free older adults will permit an unambiguous assessment of the pk-pd and neurocognitive and other side effects of a single dose of oral methadone without the complications of pain, drugs and other disease variables. Our results will provide information that allows clinicians to make informed and evidenced based decisions with regard to pain management & methadone maintenance therapy in older adults.

Resulting articles & projects:

  • Findings from this pilot study facilitated the design of a subsequent study examining the impact of alcohol consumption on pain and pain medication in older adults. The submission of this re-formulated project was successful in obtaining funding from the NIH Institute on Aging. NIA R01 AG047979 (Cherrier-PI), “Cognitive, Behavioral and Aging Effects of Opioids in Alcohol Users. ” The major goals of this project are to measure biological and cognitive response to pain medication in older adults who consume heavy amounts of alcohol and to compare this response to middle age adults.
  • Several undergraduate students were involved in this study, obtaining research credit through Dr. Cherrier and Psychology Department, as well as employment of a newly graduated undergraduate.

An Investigation of Controlled and Automatic Cognitive Mediators of the Relation between Sexual Assault and Problem Drinking in College Women

Kristen P. Lindgren, PhD
Postdoctoral Fellow

Psychiatry & Behavioral Sciences

Debra Kaysen, PhD (Mentor)
Assistant Professor, Department of Psychiatry & Behavioral Sciences

Description: Problem drinking and sexual assault victimization occur at alarmingly high rates in college women. Approximately 40% of college women report recent episodes of heavy drinking (Wechsler et al., 2002) and approximately 25% of college women report a history of attempted or completed rape (Fisher et al., 2000). Moreover, these problems appear reciprocal in nature, with sexual assault increasing the likelihood of problem drinking and problem drinking increasing the likelihood of subsequent sexual assault (see Abbey et al., 2004; Kaysen et al., 2006). Surprisingly little research has examined potential mediators of this relation. The proposed study seeks to investigate two promising cognitive mediators, alcohol expectancies and drinking motives. Moreover, it incorporates both self-report and implicit measures of alcohol expectancies and drinking motives, thereby assessing both controlled ("deliberative," "reflective") processes and automatic ("impulsive," "spontaneous") processes. The study includes a longitudinal component, allowing evaluation of strength and direction of the relations over time. The study has a 2 (history of sexual assault) x 2 (history of problem drinking) x 4 (time) mixed measures design and will recruit a sample of 300 college women from the University of Washington. Participants will complete four, web-based assessments: baseline, two-week follow-up, three-month follow-up, and six-month follow-up. Participants will complete self-report measures of sexual assault history, alcohol consumption, alcohol consequences, alcohol expectancies, and drinking motives. The automatic counterparts of alcohol expectancies and drinking motives will be assessed with the Implicit Association Test (IAT: Greenwald, McGhee & Schwartz, 1998). Study aims include assessing (a) the strength and stability of alcohol motives and expectancies and (b) their role as mediators of sexual assault and problem drinking. Study findings are expected to extend theories of problem drinking, increase the ability to predict problem drinking cross-sectionally and longitudinally, and suggest additional targets for intervention.

Resulting articles & projects:

  • This award directly led to a new award from NIAAA, ­the K99/ROO Pathway to Independence award, funded for 2008-2013. The ADAI-funded research was the core of the project proposed for the K99 portion of the NIAAA grant [1K99AA017669-01].
  • The subsequent NIAAA grant has produced numerous published articles.
  • Lindgren KP, Mullins PM, Neighbors C, Blayney JA. Curiosity killed the cocktail? Curiosity, sensation seeking, and alcohol-related problems in college women. Addict Behav 2010 May;35(5):513-6. [PubMed abstract]

Use of Social Networking Websites for Identification and Screening of Problem Drinking in Adolescents

Megan A. Moreno, MD, MSEd
Fellow in Adolescent Medicine, now at Seattle Childrens Hospital

Adolescent Medicine

Dimitri Christakis, MD, MPH (Mentor)
Professor, Department of Pediatrics
Director, Child Health Institute

Description: Alcohol use among adolescents is common and has many serious consequences. Identification of adolescents at risk for problem drinking remains challenging. Adolescents infrequently seek health care, and many physicians do not screen adolescents for alcohol use. Most U.S. adolescents have Internet access, and over half use social networking websites such as MySpace.com to create and peruse individual web profiles. Some teens reference alcohol use on their MySpace personal web profiles. This public display of alcohol use may be an indicator of problem drinking. Social networking websites may provide a new setting to identify teens at risk for problem drinking and to offer alcohol screening. This study will use MySpace.com to identify adolescents who display alcohol use information on their profiles and offer them Internet CRAFFT screening via email invitation. Our long-term research plan is to develop and test Internet-based interventions to identify and reduce problem drinking in adolescents. In advance of that goal, this study has the primary object of determining what proportion of adolescents contacted via MySpace will complete internet CRAFFT screening. Other specific aims include exploring whether response rates differ by email approach (physician versus research assistant) or by respondent's gender. We will determine what proportion of adolescents completing the CRAFFT screen test positive for problem drinking. We will determine whether an association exists between CRAFFT scores and alcohol references on subjects' MySpace profiles, as well as whether there are differences in respondents and non-respondents to CRAFFT screening invitations by examining their MySpace profiles. The results of this evaluation have the potential to impact public health practice by demonstrating how to expand adolescent health screening to the Internet using public websites and email communication. Furthermore, our findings will provide requisite pilot data in pursuit of extramural funds.

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:

  • As a result of this ADAI funded project, Dr. Moreno submitted two successful grants to NIAAA: "Facebook: A Screening Tool to Identify Alcohol Use Among Female College Freshmen" [5R03AA019572-02] and "Use of Social Networking Web Sites for Problem Drinking Screening in Adolescents" [5R21AA017936-02]
  • Moreno MA, Briner LR, Williams A, Walker L, Christakis DA. Real use or "real cool": adolescents speak out about displayed alcohol references on social networking websites. J Adolesc Health 2009 Oct;45(4):420-2. [PubMed abstract ]
  • Published abstract at the 2009 Society for Adolescent Medicine conference: Moreno MA, Briner LR, Williams A, Walker L, Christakis DA. "Real Cool: Adolescents Speak Out About Displayed Alcohol References on MySpace."
  • "Teens Think Drinking on MySpace, Facebook Is Real." US News & World Report, Oct 30, 2009.
  • "Under the influences: When teenagers boast on Facebook". Milwaukee Journal Sentinel, Nov. 23, 2009.

Motivational Consequences of Nitrous Oxide Exposure in Rats

Douglas S. Ramsay, DMD, PhD, MSD
Professor and Chair

Dental Public Health Sciences

Description: This proposal seeks to better understand the motivational consequences of drug effects. A drug can act to force a regulated variable away from its defended level, which triggers "corrective" physiological and behavioral responses. In contrast, some drugs alter the "set-point" of the dependent variable, which activates physiological and behavioral responses that move the variable to the new defended level. Many drug addiction theories posit a "homeostatic-corrective" regulatory response to drug effects. One current theory suggests that chronic drug use may force a regulated variable away from its defended value but in a direction opposite to the drug's pharmacological effect. Theoretically, such a change could motivate increased drug consumption so that the drug effect can return the variable to the defended level. It is important to determine whether this is a forced "overcorrection" that motivates corrective counter-responses or whether it is a regulated change that moves the variable to the new set-point. Although nitrous oxide (N20) initially causes a hypothermic core temperature (Tcore), this hypothermia can change to hyperthermia during subsequent N20 exposures with unknown motivational consequences. An accepted method to distinguish whether such changes represent forced versus regulated phenomena is to let the rat choose an ambient temperature (Tamb) in a temperature gradient (thermocline). If a drug-induced hypothermia is forced, the rat will be motivated to resist the drug effect and move to a warmer Tamb. If the hypothermia is regulated, the rat will be motivated to assist the change by moving to a cooler Tamb. This project represents our first attempt to develop this methodology. Rats receive N20 and placebo (within-subject cross-over design) in a gas-tight thermocline where they select their preferred ambient temperature and thereby indicate the motivational consequences of N20's effect on temperature. This research will provide preliminary data to support a broader NIH grant proposal.

Resulting articles & projects:

  • This project provided preliminary data which supported a successful NIDA grant proposal, ""Drug-Induced Allostasis and Its Motivational Effects During Adolescence." Total direct costs are $1,100,000 (9/15/08 -5/31/13) [1R01DA023484-01A2

2007 October

Modeling Longitudinal Stability of Heavy Episodic Drinking and Smoking among College Students Using the Theory of Planned Behavior

Susan E. Collins, PhD
Postdoctoral Fellow

Psychiatry & Behavioral Sciences

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

Description: Smoking and heavy episodic drinking (HED) among college students remain a cause for concern because these behaviors are highly correlated with later substance-use disorders, psychosocial problems, and in the long-term, can increase health risks multiplicatively. In order to achieve a better understanding of these risk behaviors and identify potential points for intervention, researchers have suggested the systematic observation and modeling of natural substance use trajectories and potential theoretical correlates (Piasecki, Fiore, McCarthy, & Baker, 2002; Sobell, Ellingstad, & Sobell, 2000). The proposed longitudinal study will answer this call to research by using the theory of planned behavior (TPB) in combination with latent transition analysis (LTA), an innovative longitudinal modeling technique, to predict college students' longitudinal smoking and drinking patterns as well as subsequent substance-use problems. College students (N ? 780) at the University of Washington and Loyola Marymount University who report 30-day alcohol-use prevalence will comprise the proposed study sample. Smoking, drinking and components of the TPB, including attitudes, perceived behavioral control, subjective norms and behavioral intention, will be assessed using online data collection at baseline. Because research has shown that college students' smoking primarily occurs in heavy-drinking situations, the TPB components will focus on students' beliefs about and intentions to engage in HED. One- and three-month online follow-ups will assess substance use and subsequent outcomes (i.e., problem drinking, extent of nicotine dependence). This study will contribute to the literature by using confirmatory, simultaneous testing of a multicomponent theory to model the influence of theoretical correlates on college smoking and drinking and will thereby identify points of intervention for college students who are at higher risk for substance-use problems. Pilot data from this study will build the foundation for a future study that will aim to tailor interventions based on key predictors of higher vs. lower risk substance use trajectories.

Resulting articles & projects:

  • Based on the findings and experience gleaned in this project, Dr. Collins was able to successfully obtain funds to further her research on college drinking: NIAAA K22 Career Transition Award (1 K22 AA018384-01).
  • Collins SE, Witkiewitz K, Larimer ME. The theory of planned behavior as a preductor of growth in risky college drinking. Manuscript submitted for publication. (2010)
  • Collins SE. The theory of planned behavior as a model of heavy episodic drinking among college students: Initial findings. Paper presented at the Alcohol Research Training Seminar, April 2010.