Peter M. Monti - US grants

The long-term goal of this research program is to reduce relapse among cocaine abusers by investigating more effective treatment interventions. The theoretical framework guiding this work is based on: 1) a coping skills model of relapse derived from social learning theory, and 2) the belief that finding key individual difference variables for matching patients to treatment will enhance treatment efficacy. Specific aims of this study are to test the effectiveness of family social skill training derived from social learning theory for treating cocain abusers, and to examine variables of possible utility in future patient-treatment matching studies. These variables include differences in coping skills, family history of substance abuse, depression, trait anxiety, and concurrent alcohol abuse. A two-group controlled design will be used, with family social skills training being compared to an attention-placebo control group (family discussions) when both are added to standard inpatient substance abuse treatment. Assessment includes multiple measure of drug and alcohol use at 6, 12, and 18 month follow-up interviews, measures of coping skills on role-play tests, and measures of family and psychosocial functioning. These assessments will allow evaluation of treatment effects and relapse, and will also permit evaluation of the role of various prognostic and mediating variables.

The long-term goal of this research program is to reduce relapse among alcohol abusers by determining more effective treatment interventions. The theoretical framework guiding this work is based on: 1) a coping skills model of relapse derived from social learning theory, 2) models of classically conditioned reactivity to alcohol stimuli, and 3) an assumption that matching patients to treatment of the basis of key individual difference variables will enhance treatment efficacy. Specific aims of this study are to test the effectiveness, separately and combined, of two forms of intervention: family social skills training derived from social learning theory, and cue exposure with response prevention derived from respondent learning theory. Another major aim is to examine a treatment-matching hypothesis by determining whether individual differences in cue reactivity and coping skills interact with the treatments to provide differential outcome. A 2 X 2 stratified randomized design will be used with one factor being family social skills training and the other factor being cue exposure treatment. Each cell will be stratified on initial cue reactivity to ensure an equal number of low an high cue reactors in each condition. This will also allow later cue reactivity X cue exposure analyses to test one matching hypothesis. The control for the social skills training will be a discussion group and the control for the cue exposure treatment sessions will involve films and reading. All treatments and controls will be added to standard inpatient alcoholism treatment. This design will allow us to investigate the effects of each treatment alone and in combination as compared to standard inpatient treatment while controlling for time and expectancy. Assessment includes multiple measures of alcohol use including 6, 12, and 18 month follow-up interviews, measures of coping skills and cue reactivity previously developed in this laboratory, and measures of family and psychosocial functioning. These assessments will allow evaluation of treatment effects and relapse, retrospective investigation of additional matching hypotheses, and evaluation of the role of various prognostic and mediating variables.

The long-term objective of this research is to enhance cross-addictions treatment recommendations by elucidating the relationship between smoking and drinking among alcoholics under carefully controlled experimental conditions. Findings will contribute both to our basic knowledge concerning some of the relationships between drinking and smoking and to knowledge about factors that are likely to increase or decrease the probability of relapse. The specific aims are to: 1) investigate alcoholics' expectancies about the interaction of smoking with drinking and with alcohol treatment, and to relate the expectancies to post-treatment substance use, 2) investigate the effects of smoking on reactions such as urges to drink elicited in response to alcohol cues, and 3) investigate the effects of the reactivity to alcohol cues on subsequent smoking rate. Three studies are planned. Study 1 will use interviews and questionnaires to assess expectancies about the effects of smoking, of drinking, of the interaction of smoking and urges to drink, and beliefs about the effects of smoking and of smoking cessation on the process of recovery from alcohol treatment. Data on smoking and drinking rates will be obtained both during treatment and at 3 month follow-up so that the expectancies can be related to short-term change in drinking and smoking rates. In Study 2, urges to drink and other aspects of cue reactivity will be elicited by exposing alcoholics to alcohol cues (a control group will be exposed only to water cues), then subjects will either smoke their usual cigarette or only read magazines in order to determine the effects of smoking on elicited cue reactivity. In a third study the effect of alcohol reactivity on smoking will be assessed by exposing alcoholics to either alcohol or water cues, then assessing the subsequent rate and topography of smoking. Assessments of alcohol reactivity in these studies will include both self report and psychophysiological measures. Assessments of smoking will include topography, rate, and expired alveolar carbon monoxide. Individual difference factors will be assessed to investigate mediating variables. Results of these studies will provide groundwork for making more informed decisions as to whether it would be more effective to encourage alcoholics to quit smoking concurrently with alcoholism treatment or wait until sobriety is stabilized. Furthermore, individuals may be identified who could be matched to immediate versus delayed smoking interventions, and expectancies about the interaction of tobacco and alcohol can be targeted for modification in treatment.

The long-term objective of this research is to enhance cross-addictions treatment recommendations by elucidating the relationship between smoking and drinking among alcoholics under carefully controlled experimental conditions. Findings will contribute both to our basic knowledge concerning some of the relationships between drinking and smoking and to knowledge about factors that are likely to increase or decrease the probability of relapse. The specific aims are to: 1) investigate alcoholics' expectancies about the interaction of smoking with drinking and with alcohol treatment, and to relate the expectancies to post-treatment substance use, 2) investigate the effects of smoking on reactions such as urges to drink elicited in response to alcohol cues, and 3) investigate the effects of the reactivity to alcohol cues on subsequent smoking rate. Three studies are planned. Study 1 will use interviews and questionnaires to assess expectancies about the effects of smoking, of drinking, of the interaction of smoking and urges to drink, and beliefs about the effects of smoking and of smoking cessation on the process of recovery from alcohol treatment. Data on smoking and drinking rates will be obtained both during treatment and at 3 month follow-up so that the expectancies can be related to short-term change in drinking and smoking rates. In Study 2, urges to drink and other aspects of cue reactivity will be elicited by exposing alcoholics to alcohol cues (a control group will be exposed only to water cues), then subjects will either smoke their usual cigarette or only read magazines in order to determine the effects of smoking on elicited cue reactivity. In a third study the effect of alcohol reactivity on smoking will be assessed by exposing alcoholics to either alcohol or water cues, then assessing the subsequent rate and topography of smoking. Assessments of alcohol reactivity in these studies will include both self report and psychophysiological measures. Assessments of smoking will include topography, rate, and expired alveolar carbon monoxide. Individual difference factors will be assessed to investigate mediating variables. Results of these studies will provide groundwork for making more informed decisions as to whether it would be more effective to encourage alcoholics to quit smoking concurrently with alcoholism treatment or wait until sobriety is stabilized. Furthermore, individuals may be identified who could be matched to immediate versus delayed smoking interventions, and expectancies about the interaction of tobacco and alcohol can be targeted for modification in treatment.

The objective of this research program is to improve treatment for alcoholism by investigating the combined effectiveness of a proven type of psychotherapy, cognitive behavioral therapy (Coping Skills Training and Cue Exposure Treatment - CSTCET), with pharmacotherapy (Naltrexone), in a balanced 2X2 factorial randomized clinical trail. Recent advances in cognitive behavioral and pharmacological theories and research suggest that a clinical trial of the separate and interactive effectiveness of these treatments on drinking over 72 weeks. Matching hypotheses regarding cue reactivity and naltrexone will be investigated. Finally, theoretically important mediating mechanisms such as cue reactivity (e.g., urge to drink and salivary response) and appetitive responses (e.g., hunger and weight) will be assessed, and exploratory analyses will be conducted. 160 male and female alcoholics, recently detoxified for their alcohol use, will be recruited into this study. Subjects will receive 2 weeks of CSTCET or a control treatment while inpatients and will then receive either naltrexone or placebo for 12 consecutive weeks as outpatients. Assessment of cue reactivity will occur at the start of the psychological treatment condition, and at its completion, to insure that subjects have learned certain skills prior to pharmacotherapy. This assessment will be repeated at the end the medication condition, after subjects have utilized these skills while on the medication in the natural environment. Subjects and their significant other will be contacted for follow-up at 24, 48, and 72 weeks after all treatment is completed. This study will go beyond currently available data on both factors under study (CSTCET and medication) by being the first test of the interaction between these cutting edge treatments with alcoholics severely impaired enough to have been hospitalized. It will also be the first test of a theoretically relevant matching variable (cue reactivity) with naltrexone. Finally, the study will tell us more about the long term interaction of CSTCET and naltrexone by conducting follow-ups for a period of time considerably longer than any other available in the naltrexone literature.

The long term objectives of this program are to develop effective intervention approaches for adolescent drinking and driving and for the behavior of riding with a drinking driver by evaluating promising treatments derived from cognitive behavioral social learning theory. Current approaches to behavior change in this area rely on driver education programs and secondary prevention programs that have shown rather modest results. While Emergency Departments are another potential locus for intervention, no studies have as yet intervened directly with adolescents following an alcohol-related motor vehicle crash. Studies of individual risk factors and the role of parents in preventing drinking and driving point to the importance of these considerations in designing effective interventions. Motivational interviewing (MI) has been selected as the intervention to be studied because of the likely state of readiness to change in this high risk population and because of the demonstrated effectiveness of this approach in reducing drinking among adults that had not sought treatment for drinking. Given their history, these motivation to change their behavior. The MI will intervene with both the adolescents and their parents, to maximize the effectiveness of the intervention. The proposed work will extend our group's track record of careful assessment and treatment interventions with adults and adolescents to an risk group of adolescent drinking drivers, their passengers, and parents. A three group (MI with multiple follow-up versus standard care with multiple follow-up versus standard care with a single follow-up) repeated measures analysis of covariance design will test the primary hypothesis that a MI will significantly reduce the incidence of drinking and driving or riding with drinking drivers. Since within-group factors may differentially influence outcome, alcohol use severity will be considered as a potential matching variable. The comparison of standard care with multiple versus single follow-ups allows investigation of any reactive effects of repeated assessment on alcohol use during motor vehicle use. As assessment instruments in this area are weak, instrument development is also a focus of the work to be accomplished. Outcome measures will assess changes in alcohol use during motor vehicle use plus changes in drinking behavior per se, risk-taking behavior, and injuries, as reported by both parent and adolescent 3,6 and 12 months after the intervention. The importance of this work is its potential for providing a cost- effective brief intervention to reduce deaths and injuries among adolescents due to alcohol use combined with motor vehicle use.

Tobacco smoking by adolescents poses a major health threat, with 90% of adults having initiated smoking before the age of 18. The long-term objective of this research is to investigate ways to effect decreases is smoking among adolescents. The major purpose of this study is to examine whether brief, individual motivational interviewing (MI) treatment in a hospital emergency department (ED) followed by a booster session one week later can be effective in changing subsequent smoking behavior in a population of adolescent ED patients. The effectiveness of the intervention will be determined by randomly assigning adolescent smokers to either standard care of MI plus booster, and then comparing groups at 1, 3, 6, and 12- month follow ups on self-report and biochemical measures. Motivational Interviewing has been selected as the experimental intervention because of its demonstrated promise as a brief intervention in medical settings, and its appropriateness for a population of smokers which will include a full range of motivation to change. MI's effect on behaviors and cognitions related to quitting smoking will also be assessed, including: effects on number of quit attempts, total duration of abstinence, treatment seeking for smoking cessation, motivation to change smoking behavior, negative evaluation of smoking consequences. In order to identify individuals most likely to benefit from MI, the mediating effects of several baseline characteristics will be explored, including level or nicotine dependence, stage of motivation to change smoking behavior, depressed affect, and use of other drugs. Instrument development is also a focus of the work to be accomplished. The importance is this work is its potential for providing a cost-effective brief intervention to reduce smoking among adolescents. Because it is implemented in the ED, it reaches a high-risk population of adolescents that would be difficult to reach elsewhere, i.e., youth who have dropped out of school and youth who do not receive health care outside the ED setting.

The long term objectives of this program of research are to develop effective interventions for reducing problem drinking and associated problems among adolescents and young adults and to further enhance intervention approaches by identifying effective elements of treatment derived from cognitive behavioral social learning theory. Current approaches to behavior change in this area frequently rely on school-based primary preention programs that do not address cessation/reduction issues for adolescents who are already drinking, rarely address motivational issues related to use and abuse, and cannot target school dropouts. Recently, two studies have shown Motivational Interviewing (MI) to be effective with alcohol-involved adolescents when compared to a control or no intervention condition, but have shown greater harm-reduction effects than alcohol consumption effects. In addition, mechanisms of MI have not been elucidated. The major purposes of this study re to compare MI to a minimal contrast condition in which personalized feedback is provided, and to determine if additional booster sessions will enhance outcomes. The population is older adolescents who have been treated in an Emergency Department (ED) following an alcohol-related event. Thus, school dropouts, a high-risk population, will be included in the study. A 2 (MI versus Feedback Only) x 2 (two booster sessions versus no boosters) factorial design will be used to examine whether a MI combined with booster can effectively change subsequent alcohol use and alcohol problems. Experimental manipulations will be evaluated 6, 9, and 12 months after baseline intervention. The study design has several strengths: (1) it will enable an investigation of the main effects of MI versus Feedback Only, providing a more stringent test of the active ingredients of MI than our current competitive segment permitted; (2) it enables an evaluation of the effects of continued contact as a separate factor; and (3) it allows a test of the interaction between baseline intervention type and booster contact. A secondary purpose of the study is to use explicit mediational analyses, tested within a Structural Equation Modeling framework, to examine the hypothesis that stge of change, use of behavioral alcohol reduction strategies, and alcohol treatment seeking will mediate the relationship between intervention and outcome. Finally, the study will determine whether the diagnosis of alcohol abuse or dependence affects responsivity to our intervention. In addition to its potential contribut8ion to theory, the importance of this work is its potential for providing a cos-effective brief intervention at a "teachable moment" to increase high-risk patients' interest in reducing harmful drinking and related risk-taking behaviors.

APPLICANT'S ABSTRACT: Naltrexone treatment reduces drinking rates for alcoholics, especially for those who lapse. However, the mechanisms that may mediate naltrexone's effects on drinking are not well understood. Effects on urges may provide one mediating mechanism. Clinical trials suggest that naltrexone reduces urges to drink, and lab studies with alcohol showed that naltrexone reduced the probability of experiencing cue-elicited urges to drink. Effects on the reinforcing effects of alcohol after taking a drink may provide another set of mediating mechanisms. Lab studies with heavy drinkers found brief administration of naltrexone to decrease the pleasurable effects of drinking, increase latency to a second drink, and reduce drinking rates. Naltrexone may thus reduce additional drinking due to reductions in positive reinforcement. The overall primary objectives are to determine whether naltrexone: (1) reduces urges to drink and initial reactions to drinking among heavy drinkers in the natural environment, using ecological momentary assessments (EMA), and in laboratory assessments of urge in response to alcohol cues, and (2) reduces drinking rates in this population. Therefore, we propose to provide 3 weeks of naltrexone (50 mg/day) or placebo administration to heavy drinkers in a 2-group randomized placebo-controlled design. All will participate in a week of baseline recording, a week of placebo leadin, then 3 weeks randomized to medication condition with medication management sessions. All participants will use palmtop computers daily to record urges to drink, environmental circumstances in which urges occur, drinking behavior, and reactions to drinking. All will participate in a lab assessment of alcohol cue reactivity after one week on the medication. This study will be the first to investigate the effects of naltrexone with heavy drinkers in a fine-grained analysis in the natural environment. The results will add important information about some of the hypothesized mechanisms of naltrexone's effects and about the relationships among environmental circumstances, urges and drinking behavior. Since heavy drinkers pose a substantial risk to other people and cost to society, investigation of the effects of naltrexone on this population may ultimately lead to interventions for heavy drinkers who need to modify their drinking rates.

DESCRIPTION (Provided by applicant): The purpose of our program is to provide post-doctoral training for biomedical, behavioral, health care and other public health scientists who wish to pursue a career in alcohol research. The training program focuses on intervention research that relates to early intervention and treatment outcome of alcoholism and alcohol abuse. These interventions are approached from multiple disciplinary perspectives: social psychology, medical sociology, cultural anthropology, clinical psychology, medicine, psychiatry, public health and community medicine. The program emphasizes the need to develop and test more sophisticated theories of intervention, the importance of the biological, psychological, social and cultural environment in which the intervention occurs, and the need for development of more refined methods for measuring person, intervention and impact variables. Applicants consist of individuals trained in several behavioral and social science specialties including psychology, sociology, and anthropology, as well as, health care trainees interested in alcoholism intervention research: medicine, clinical psychology and other health service specialties. Candidates are selected on the basis of their interests and potential for doing outstanding alcoholism research. Four applicants will be selected annually for two-year fellowships. This will yield 10 fellows in residence on an ongoing basis. Training is accomplished through a combination of seminars and research apprenticeships in ongoing treatment and community settings. Upon completion of the program, trainees are equipped to conduct independent high quality treatment/intervention research in alcoholism and alcohol abuse. The training facilities consist of the Center for Alcohol and Addiction Studies, teaching hospitals of the Brown Medical School and a diverse array of community settings accessible to trainees through the Center, the Department of Community Health and the Department of Psychiatry and Human Behavior. Several of the teaching hospitals have comprehensive alcohol abuse treatment programs, as well as research facilities and resources for conducting treatment research. Training faculty have developed strong collaborative ties with community agencies which facilitate the conduct of early intervention research. A new addition to the training program is the collaboration between this training program and those supported under other T32 programs in the Department of Psychiatry and Human Behavior.

DESCRIPTION: (provided by applicant) Demonstrating sustained abstinence following adolescent smoking cessation intervention has remained an elusive goal, particularly for adolescents with heavier smoking patterns. The major purpose of this study is to improve smoking cessation rates among adolescent smokers by promoting both intrinsic and extrinsic motivation to change. This randomized clinical trial will use a 2 x 2 between groups factorial design to investigate the separate and combined effects of two primary intervention factors for adolescent smokers (ages 14-19), recruited from school settings, who are low in motivation to change their smoking. The first factor, the Reinforcement Component, contrasts contingency management (CM), in which adolescent smokers will be reinforced for reductions in smoking behavior, to the comparison intervention of noncontingent reinforcement (NR), in which adolescents will receive reinforcers regardless of smoking levels. The second factor, the Psychosocial Component, contrasts motivational enhancement therapy (MET) to the comparison intervention of progressive muscle relaxation (REL) to quit smoking. We hypothesize that the combination of CM and MET will be instrumental in increasing both intrinsic and extrinsic motivation to change smoking behaviors. Efficacy will be determined by randomly assigning adolescent smokers to one of four conditions: (1) CM + MET, (2) CM + REL, (3) NR + MET, or (4) NR + REL. Groups will be compared at 1-, 3-, and 6-month follow-ups periods of self-report and biochemical measures of smoking. The separate and combined effects of MET and CM on changing behaviors related to smoking will be assessed, including percent days abstinent, abstinence duration, and biochemical measures. Mechanisms of change will be explored through examination of potential mediating effects of self-efficacy and motivation to change smoking on outcome. By integrating two behavioral interventions, this work has the potential to reduce smoking rates among heavier smoking adolescents and enhance our understanding of mechanisms of action.

[unreadable] DESCRIPTION (provided by applicant): Alcohol-positive trauma patients are more likely to be readmitted to a trauma center or die from a subsequent injury than are alcohol-negative trauma patients. Despite their increased risk, there are few empirically-supported treatments available for this population. Admission to a trauma unit may represent a "teachable moment", where patients are particularly willing to discuss their alcohol use. Therefore, interventions delivered in the trauma unit may be particularly effective. Motivational Interviewing (MI), a brief, directive, non-confrontational intervention, has demonstrated some promise in this setting. Further, inclusion of a significant other (SO) in prolonged, intensive alcohol treatment appears to improve treatment retention and efficacy. Although inclusion of an SO in MI has been suggested, there are few data to support this endorsement. Accordingly, this study (N=300) will address whether motivational interviewing including both the trauma patient and an SO can more effectively decrease and maintain reductions in alcohol use and alcohol-related problems 6 and 12 months following discharge from the trauma unit than MI with the individual patient or an assessment-only condition. The 2 MI groups will each receive 2 intervention sessions timed to occur in the hospital, and 1 booster session, occurring 1 month following discharge. In the assessment-only condition, patients will receive only assessment of their drinking at baseline. This proposal will allow us to address the next phase of our program of research designed to develop easily disseminable treatments for these high-risk populations in medical settings. This study will also address potential mediators (motivation to change alcohol use, self-efficacy, alcohol treatment attendance, and social support for abstinence) and moderators of MI effects. The cost-effectiveness of the intervention will also be addressed. Thus, this study will address both a significant public health problem and provide important information about MI mechanisms that may be relevant to the broader addiction treatment community. [unreadable] [unreadable]

Topiramate (TOP) has been reported to be efficacious in reducing drinking rates in men and women with alcohol dependence (Johnson et al.,2003;Rubio et al.,2004). Recent preclinical studies are also encouraging. The fact that TOP reduced drinking and increased periods of abstinence in non-abstinent alcoholics suggests that it is effective for initiating abstinence (Johnson et al.,2003). However, while significant differences on self-reported drinking measures started at the 200 mg/day dose in week 6 of Johnson et al. (2003), doses continued to increase up to week 8 so the effects of time and dose were confounded. Because TOP requires a slow titration and because the probability of experiencing side effects increases at doses higher than 200 mg/day, it is of considerable clinical importance to determine at what dose TOP has the most favorable benefit-to-side effect ratio. In addition, mechanisms that mediate TCP's effects on drinking are not understood. Evidence suggests that attenuation of craving may mediate TOP'S effects, however, no laboratory studies have assessed urge to drink while on TOP and studies of other putative behavioral mechanisms of effects have not been done. Further, studies have yet to identify which individuals are most likely to benefit from TOP. Improvements in pharmacological treatments may occur through identification of individual difference variables associated with differential treatment response. We propose to randomize alcohol dependent individuals not seeking treatment to one of three conditions in a three-group, placebo-controlled design: (1) TOP (200 mg/day);(2) TOP (300 mg/day);(3) placebo. As in our current segment, both Ecological Momentary Assessment (EMA) and cue reactivity (CR) will be measured. EMA will be conducted by having all participants use palm top computers daily for three weeks to record drinking behavior, urges to drink, and environmental circumstances in which urges occur. CR will be assessed in laboratory. Effects of potential genetic moderators of TOP response will be examined, as will certain mediators. This project will provide an efficient and comprehensive analysis of the effects of TOP on drinking and craving and will add important new information about putative biobehavioral mechanisms. Results will afford a better understanding of whether large-scale randomized clinical trials with long-term follow ups are warranted.

DESCRIPTION (provided by applicant): This is a new application for a Senior Research and Mentorship Award (K05). The candidate, Peter M. Monti, Distinguished Professor of Alcohol and Addiction Studies, Director, Center for Alcohol and Addiction Studies and Head of the Behavioral and Social Sciences Section at Brown University, proposes an initial period of intense research mentoring to four outstanding Brown University scientists in his Center and a shift in his research program to youth and young adults. Therefore, Dr. Monti proposes to transition from a VA Senior Career Scientist Award to the K05. Mentees and Mentoring Plan. One of the proposed mentees, Don Operario (a social psychologist) was recently recruited from Oxford University and is in a tenure-track position. The other two proposed faculty mentees, Robert Miranda (a clinical psychologist) and Tara White (a neuroscientist) are on a "research" track. While all three have excellent publication records, only Miranda has published alcohol papers and has received funding from NIAAA (a K23 and 2 R21s). Operario and White are NIDA-funded. None have been funded at the R01 level from NIAAA, though all three have demonstrated strong interest in becoming alcohol researchers. Miranda is furthest along, though both Operario and White have submitted alcohol applications as part of the candidate's pending P60 Center Grant Proposal. The fourth mentee, Margie Skeer (a social epidemiologist) is a postdoctoral candidate working with Monti. She too has a strong publication record. However, she has only just published her first alcohol manuscript, though she has indicated interest in alcohol, as this was her reason for coming to Brown. Mentoring goals for all applicants involve providing both targeted and general guidance and support for grantsmanship, the development of alcohol research programs, and more general professional development issues including feedback on how to mentor their own trainees. Importantly, all four mentees have been incorporated into the applicant's research program which is moving in the direction of youth alcohol intervention and the study of alcohol/HIV interactions. The applicant intends to gain complementary expertise in this area as well as in neuroscience and MRI modalities - all topics of his P60. With respect to the Research Plan, the applicant intends to continue to focus on a research agenda that is broad and yet focused on treatment mechanisms, pharmacotherapy, contextual factors and individual differences. Using his existing data sets he proposes to study mediators and moderators of treatment outcomes and the assessment of daily drinking behavior in the context of his brief intervention work. In addition he will add a study of lab-based alcohol effects onto his ongoing trial of topiramate for heavy drinkers, thus enabling the study of the effects of topiramate and drinking both in the lab (new data to be collected) and in the natural environment (through Ecological Momentary Assessment data that are already collected as part of his ongoing R01). Finally, as funding for his pending P60 application becomes clearer, he will begin pertinent pilot work on aspects of this project. PUBLIC HEALTH RELEVANCE: Advancing biopsychosocial approaches to alcohol treatment and mentoring has the potential to influence public health by reducing alcohol use in youth through improved early intervention and treatment. More and better mentored alcohol treatment scientists will facilitate the goal of reduced use in youth.

DESCRIPTION (provided by applicant): Linkages between alcohol use and HIV/sexual risk behaviors have been observed in multiple groups and each behavior has been successfully treated individually. Indeed, some studies suggest these behaviors can be successfully treated together. The Emergency Department (ED) provides a venue through which many patients with multiple risks are treated. Yet, to date no study has addressed these behaviors together in an ED, where admission may represent an opportunistic moment when patients are particularly willing to discuss these risky behaviors. Motivational Interviewing (MI) has demonstrated promise with alcohol risk in the ED in several of our previous studies, and has shown promise with sexual risk populations as well. Accordingly, this study (N=302) will address whether a two session multiple risk MI can more effectively decrease and maintain reduction in alcohol use, alcohol related problems, and sexual risk taking following discharge from the ED than Brief Advice (BA). Baseline, MI Session 1 and BA will be administered in the ED. MI Session 2 will occur 7- 10 days following MI Session 1. Follow-ups will be conducted at 3, 6 and 12 months. This proposal will allow us to address the next phase of our program of research that has been designed to develop easily disseminable treatments for high-risk populations in medical settings. This study will also address potential mediators (motivation to change risk taking, self-efficacy) of MI effects. We will also examine whether reductions in sexual risk associated with MI compared to BA are accounted for by reduced drinking. A tertiary aim will examine the moderating effect of co-occurring substance use on outcomes. The cost-effectiveness of the interventions will also be addressed. Thus, this study will address two significant Public Health problems and provide significant information about MI mechanisms that may be relevant to the treatment community. PUBLIC HEALTH RELEVANCE: This brief alcohol and sexual risk taking intervention has the potential to influence the public health by reducing alcohol use and sexual risk taking behavior in individuals who are seeking treatment in an Emergency Department.

Alcohol use contributes to morbidity and mortality associated with HIV in numerous ways including (a) reducing antiretroviral medication adherence and efficacy, (b) contributing to worse virologic outcomes and immune functioning, (c) exacerbating liver dysfunction and hepatitis co-infection, and (d) exacerbating neurocognitive deficits associated with HIV. In addition, alcohol use among both HIV-infected and uninfected individuals is implicated in high-risk sexual behavior that leads to HIV transmission. Given multiple pathways through which alcohol impacts HIV morbidity, mortality and transmission, we propose an integrated, multifaceted, interdisciplinary approach to forward science on alcohol/HIV interactions and inform clinical approaches to caring for people living with HIV and efforts to prevent HIV transmission, both nationally and internationally. The overall aim of this Comprehensive Alcohol Research Center (CARC) is to conduct and disseminate multidisciplinary state-of-the-art research on biobehavioral interactions between alcohol and HIV and on interventions to reduce alcohol use among HIV-infected patients and individuals at high risk for HIV transmission. The CARC has 9 integrated parts: an Administrative Core , four Research Components, two Scientific Cores (Virology and Biostatistics), a Pilot Projects Component, and an Education/Dissemination Component that serves as a national resource for training and dissemination. Research activities address overlapping hypotheses regarding key variables (alcohol use, virology, hepatic function, neurocognitive function, use of antiretroviral therapy, and high-risk sexual behavior) and interrelationships among these variables using diverse methodologies (both animal and human research) and populations. These activities provide an integrated body of innovative alcohol/HIV research that can yield far greater total public health impact than any or all of them could if conducted independently. Further, this CARC will serve as the nexus for integration of alcohol/HIV science across proposed components, innovative pilot projects, complementary studies, and with other NIAAA Centers, yielding new insights into interactions between alcohol and HIV and into interventions to reduce drinking among those with HIV and others at risk for transmission.

Project Summary The overall aim of the Administrative Core (AC) of the Program Project, the Alcohol Research Center on HIV (ARCH), is to provide the scientific, administrative, and financial support needed to conduct the best science on the bio-behavioral interactions between alcohol and HIV and to evaluate interventions to reduce drinking among those with HIV and those at high risk for HIV transmission. The ARCH contains 6 integrated parts that make unique contributions to our interdisciplinary approach: 3 Research Components (RC), 2 Scientific Cores (SC), and this AC which oversees coordination of the projects, training of postdocs, and funding of promising pilot projects. Aims of the AC are (1)To provide organizational structure for effective scientific leadership; (2)To provide general administrative, fiscal and logistical management of daily operations, assure the smooth functioning of the scientific work, and maintain sound policies/ procedures; (3)To obtain external oversight from a Program Advisory Committee, seek Committee advice for major decisions/ strategic direction and evaluation of pilot projects, and arrange timely presentations to the Committee; (4)To ensure appropriate allocation to and tracking of use of core resources by RCs and Pilot Projects; (5)To provide and monitor a training/mentoring plan for all NIH-supported postdocs (6)To provide for and monitor a pilot project component that will fund 3 pilot projects, 2 of which are proposed herein; (7) To ensure collaboration and communication among ARCH and collaborating investigators, both within and outside of Brown; (8) To coordinate new extramural grant submissions consistent with the Project's mission; (9)To increase local, regional, national and international visibility of this ARCH, attract outside scientists to become active participants, and foster new collaborative and interdisciplinary relationships. The significance of the AC is that it will enhance the various RCs by allowing more comprehensive, ambitious, and innovative alcohol/HIV research projects to be conducted with high cost efficiency and greater integration of methods and measures across basic science, human laboratory, and clinical studies. Further, it will serve as the nexus for training and integration of alcohol/HIV science across RCs, pilot projects, and complementary studies, so as to yield new insights into the mechanisms and interactions of alcohol and HIV to inform treatment that will reduce drinking among those with HIV and others at high risk for transmission.

? DESCRIPTION (provided by applicant): The aim of our program is to train post-doctoral biomedical, behavioral, health care and other public health scientists to conduct research on treatment and early interventions for alcohol abuse and alcoholism. An overarching goal is to enhance the scientific reasoning skills needed to advance treatment research in alcohol abuse. From our perspective such research will benefit from interventions guided by sophisticated and fully developed theory using a multidisciplinary framework that includes the biological, psychological, social and cultural context in which interventions occur. While other institutional training programs may address treatment/early intervention research, this is the primary mission for this program. Distinctive features of our training program are: that it is interdisciplinary; tat it embraces no single ideology or theory concerning the nature of dysfunctions related to alcohol or drug abuse; that it provides training in early intervention and treatment along a continuum; and that it provides trainees with highly individualized opportunities to develop competitive grant applications and by doing so, contribute new knowledge to the base of alcohol-related dysfunction and treatment. The training experience is structured to provide individualized research experience and training, complemented by a common academic curriculum to which fellows' allocated 20% of their training time. Four distinct areas are covered in the curriculum: (1) statistics/research methodology; (2) grantsmanship; (3) ethical issues in research; and (4) a two-year sequence of formal courses covering the etiology and treatment of hazardous drinking and alcohol use disorders from varying disciplinary perspectives. We also subscribe to a research apprenticeship model under the guidance of the research mentor. The fellow's individual research training experience emerges from an individualized development plan (IDP) developed by the fellow and agreed to by his/her mentors, and reviewed and approved by the Training Committee. The program has a primary emphasis on training in innovative treatment development and clinical trials with a secondary emphasis on the translation of clinical efficacy research into services, effectiveness, and cost- effectiveness research. Our didactic and research experiences in neurobiology and neuroimaging, behavioral genetics, and alcohol administration have expanded our focus of translational research from basic to clinical research. The expected training program duration is two years but on occasion we extend this training period to three years. We offer 3rd years for fellows with less extensive training in research methods; fellows who are cross-training, e.g. adding HIV/AIDS training to a primary background in alcohol research; or for fellows in each cohort who need more time to accomplish their goals of becoming independent investigators. The program has been accepting on average 3 to 4 new fellows per year. At any given time there are likely to be 9 to 10 fellows in residence. However, in order to comply with the $500K budget cap, we are requesting funding for a total of 8 fellows at this time. This is a reduction from the 10 of previous segments of this Training Program.

Project Summary/Abstract Among men who have sex with men (MSM) in the US, annual rates of new HIV infections continue to grow, despite stability or decline among other at-risk groups. This trend is due in part to unprotected sexual behavior that poses high per-act transmission risk. Alcohol increases the risk for HIV infection among MSM, likely due to alcohol's association with increased unprotected sexual behavior. Past studies suggest that alcohol intoxication specifically co-occurs with increased odds of engaging in sexual behavior that poses high transmission risk. However, the mechanisms by which alcohol intoxication leads to increases in sex risk among MSM are poorly understood, and experimental research on alcohol's on sexual decision-making among MSM has been limited to date. An improved knowledge of these mechanisms may uncover critical opportunities to enhance existing interventions designed to reduce alcohol-related sex risk, and could point to new pathways for intervention development. Alcohol has been shown to impair executive functions (EF) that are key to regulating behavior, such as inhibitory control and executive attention, and these impairments may underlie alcohol-related increases in sex risk. Alcohol has also been shown to increase the influence of automatic processes, such as automatic affective reactions and attention biases to sexual stimuli, on behavior. As such, alcohol's tendency to increase sex risk may be due to the tendency for automatic processes to increasingly guide behavior when intoxicated, the impairment of EFs that typically moderate the influence of these processes and other impulses, or both. The proposed 3-year study will examine the effects of alcohol intoxication on sexual decision-making and behavior among MSM using a video-based sexual scenario task. This research will also examine potential mechanisms of alcohol's effects on sex outcomes, using path modeling to test indirect effects between alcohol intoxication and sex risk via EFs and automatic processes. To accomplish these goals, we will employ a between-subjects experimental design with 3 conditions (true control, placebo, and alcohol [0.08%]). The long-term goal of this research is to advance theoretical understanding of the alcohol-risky sex link, and to use this knowledge to guide a future line of research focused on developing and testing new approaches to intervention for MSM. This goal is vital given recent findings from intervention research with other behaviors suggesting that many of the processes examined in the proposed study are modifiable, and that changes in these processes produce corresponding changes in behavior. As such, this research has high potential to make critical contributions to the effort to find ways to reduce the spread of HIV among MSM.

? DESCRIPTION (provided by applicant): Alcohol use contributes to morbidity and mortality associated with HIV by (a) reducing antiretroviral therapy adherence, (b) worsening virologic outcomes and immune functioning, (c) exacerbating liver dysfunction, and (d) exacerbating neurocognitive deficits associated with HIV. In addition, alcohol use among both HIV-infected and uninfected individuals is implicated in high-risk sexual behavior that leads to HIV transmission. The Brown University Alcohol Research Center on HIV (ARCH) was funded by NIAAA in 2010 to conduct integrated interdisciplinary research on alcohol and HIV that can inform clinical approaches to caring for people living with HIV and efforts to prevent HIV transmission, as well as to serve as a regional and national resource for collaborative research on alcohol and HIV interactions. Through collaborations with the Lifespan/Tufts/Brown Center for AIDS Research and local hospitals, Fenway Health, UMass-Boston, Columbia University, University of Florida, and UCSD, we have been conducting state-of-the-art research on the combined effects of alcohol and HIV on brain structure and function and on the effects of behavioral alcohol intervention on alcohol use, sexual risk behavior, virologic outcomes, liver function, and neurocognitive function in HIV-infected men who have sex with men. The addition of two Resource Cores (U24AA022000; U24AA022003) to the ARCH have further broadened this collaborative research with a particular emphasis on two strengths at Brown, sexual minority health and mechanisms of behavior change; these cooperative agreements with NIAAA involve collaborations with Yale University, Harvard, University of Pittsburgh, University of Alabama-Birmingham, and Johns Hopkins University. This renewal application seeks to build on the progress made through the Brown ARCH expanding the scope of our research around our tightly integrated core themes. The ARCH is comprised of an Administrative Core (which also handles postdoctoral training and pilots), three Research Components, and Virology and Biostatistics Cores. Research activities address overlapping hypotheses regarding key variables (alcohol use, virology, hepatic function, neurocognitive function, and high-risk sexual behavior) and interrelationships among these variables using diverse methods including neuroimaging, biomarker analysis, behavioral interventions, technology-assisted interventions, and human laboratory-based behavioral research. These activities provide an integrated body of innovative alcohol-HIV research that can yield far greater total public health impact than any or all of them could if conducted independently. Further, the ARCH serves as a nexus for integration of alcohol-HIV science across proposed components, pilot projects, and complementary studies within Brown including investigators from all four departments in the Brown University School of Public Health and four additional departments in the Medical School. Finally, the ARCH serves as a bridge between the deep pool of investigators at Brown focusing on alcohol and HIV and investigators at the other NIAAA-funded Consortiums for HIV/AIDS and Alcohol-Related Outcomes Research.

Abstract People living with HIV (PLWH) experience increased risk for all-cause mortality at lower levels of alcohol consumption compared to uninfected individuals and higher levels of alcohol-related problems are found among African Americans despite equivalent or lower drinking. Furthermore, deleterious effects of alcohol on ART adherence and clinical outcomes have been reported in low income urban populations. Moreover, it is recommended that PLWH receive routine alcohol screening, and that evidence-based brief motivational interventions (MI) be employed when they screen positive. Indeed, MI is well-established as efficacious in reducing consumption in a broad range of patients, and adherence-focused MI has been shown to improve adherence among PLWH. While evidence supporting extended interventions targeting both alcohol and adherence is promising, multi-session interventions are generally difficult to implement with high-risk patients and no study has evaluated a single-session MI targeting both. In many HIV settings, there are barriers preventing implementation of even brief MI, such as competing intensive demands, limited resources, and lack of alcohol-specific expertise. Telehealth technology offers a viable solution. Our team has expertise in developing efficacious alcohol-focused MIs and in multi-target MI addressing the intersection of alcohol and sexual risk behavior. Further, we have an emerging understanding of the science of multi-targeted brief intervention, where co-occurring risk behaviors can be intervened upon and their reciprocal associations exploited. In particular, we have proof of concept data supporting a multi- target MI with findings demonstrating reduction in alcohol can further contribute to reductions in sexual risk behavior. We have also demonstrated logistical feasibility and acceptability of using video-conferencing technology to deliver multi-target MI in a demand-intensive setting. This proposal leverages our expertise to deliver a novel, multi-target video-conferenced MI (vMI) to racially diverse PLWH in an inner-city setting. From a translational perspective, process research is a novel means of informing intervention development, particularly when interventions are brief and there are multiple targets. For example, when developing an intervention with 2 intersecting targets for change, it is imperative to examine the ideal salience and sequencing of these targets. In Phase I, we will conduct new analyses on existing therapeutic process data to specifically examine behavioral target salience and sequencing as predictors of outcome in a brief MI with known efficacy in affecting multiple risk behaviors. Results will allow us to optimize salience and sequencing of alcohol and adherence targets in our new multi-target MI developed specifically for reaching high-risk ART non-adherent patients. Phase 1 will translate process research into a treatment-development framework to optimize a multi-target vMI to reduce consumption and increase adherence. Phase II will examine efficacy of a multi-target vMI to reduce consumption and increase adherence among dual-risk PLWH.

Project Summary/Abstract Substance use (SU) negatively affects the risk, management, progression, and outcomes of chronic disease and contributes to socio-economic and racial/ethnic disparities. Prevalence rates of medical conditions among patients with versus those without substance abuse disorders (SUDs) support this thesis. Furthermore, risks are exacerbated among those at risk for or who already have chronic medical conditions, such as people living with HIV. Though linkages between SU and disease are well documented, physiological mechanisms underlying linkages are poorly understood, largely because the literature is based on studies that use cross-sectional designs that do not allow for causal interpretations. Studies using experimental designs are needed to understand mechanisms that link SU and disease and to inform the development of targeted prevention and intervention efforts to reduce risks. We propose to establish a COBRE Center for Addiction and Disease Risk Exacerbation (CADRE) that will investigate mechanisms whereby SU impacts disease, using a combination of behavioral and physiological laboratory-based approaches across several substances of abuse. CADRE consists of four thematically and technically-linked research projects (RPs) led by an interdisciplinary group of junior faculty. Monnig will examine effects of HIV and alcohol on markers of microbial translocation, monosite activation, cytokine response, tryptophan degradation and MRI measures of inflammation. Haass-Koffler will examine the initial efficacy of oxytocin as a potential pharmacotherapy for OUD targeting stress in opioid relapse. Cioe will study effects of e-cigarettes on combustible cigarette smoking, biomarkers of smoking-related cardiac and pulmonary health, and carcinogen exposure in smokers with HIV. Aston examines effects of cannabis on RA pain, affect, and inflammation, and investigates whether effects of cannabis on pain and affect are mediated via effects of cannabis on inflammatory biomarkers. An Administrative Core will provide organizational structure, state-of-the-art mentoring, a pilot program, support diversity and health disparities work, and lead evaluation. A Clinical Laboratory Core will facilitate goals of the RPs and pilot projects, and benefit the broader Brown community by providing infrastructure and resources in the service of developing and sustaining a multi- disciplinary center. It will maximize efficiency and cost-effectiveness of this COBRE by creating linkages between CADRE RPs and other COBREs, and will create a center-wide data base of risk factors associated with development and progression of SUDs and chronic disease, available to CADRE Project Leaders (PLs) and others engaged in relevant research. PLs and pilot PLs will benefit from interdisciplinary faculty mentors who will provide guidance on research, publication, and grant preparation. The basic tenet of the proposed COBRE CADRE is that innovative interdisciplinary translational research, conducted across multiple levels of analysis, and focused on related questions using common resources and learning experiences, can not only contribute new knowledge, but also serves as the nexus and path toward independence for the next generation of scientists.