Mikhail N. Koffarnus, Ph.D. - US grants

DESCRIPTION (provided by applicant): Nearly 18% of United States adults meet criteria for alcohol dependence sometime in their lifetime, with only 24% of those individuals ever receiving any treatment for their disorder. The pervasiveness of alcohol dependence indicates a need for continued development of high-impact treatments that are both effective and easily disseminated to a broad population. Contingency management, or the delivery of monetary incentives contingent on verified abstinence, is an effective treatment for drug and alcohol abuse. However, technological barriers to accurate, frequent biochemical verification of alcohol abstinence limit the use of this technique for the treatment of alcohol dependence. Recently, a breathalyzer has been developed with technological features that make it ideally suited for use in a contingency management intervention. This breathalyzer has the capacity to remotely verify abstinence from alcohol and contains a number of features to verify the identity of the user and prevent tampering. In the present application, we propose to use this breathalyzer to facilitate a contingency-management intervention to reduce alcohol use that requires no in-person contact between the participants and the study staff during the intervention phase. To this end, we propose two specific aims. First, we will determine the feasibility of remotely-delivered contingency management trial to reduce alcohol use by using technological advances to overcome barriers in treatment delivery. We will conduct a randomized, controlled two-group feasibility study with a Contingent and Noncontingent group. The Contingent group will receive nearly immediate monetary payments over the internet each day they remotely provide negative breathalyzer samples. The Noncontingent group will receive payments each day they successfully provide samples independent of the alcohol content of those samples. Our first Specific Aim is to determine whether the contingency management intervention reduces alcohol use in the Contingent group to a greater extent than the Noncontingent group. In our second Specific Aim, we will assess participant ratings of acceptability and usefulness of these novel technologies. Poor ratings of acceptability or usefulness may suggest challenges of compliance and further dissemination. As potential treatment vehicles, it is important to assess whether the various technological tools and procedures used in this feasibility trial are viewed as effective and acceptable among individuals who are interested in reducing or ceasing their alcohol use. Together these specific aims will allow us to determine if remote, verified alcohol monitoring combined with nearly immediate, remote delivery of contingent monetary incentives is an effective treatment for alcohol dependence that is well accepted by participants.

? DESCRIPTION (provided by applicant): Illicit stimulant use and dependence remain significant problems in the United States today (NIDA, 2010). Two of the major health concerns with stimulant dependent individuals is the increased rate of sexual HIV-risk behavior in this group and a corresponding increased rate of HIV infection (e.g., Molitor et al., 1999). While the relationship between increased HIV-related sexual risk behavior and stimulant dependence is well established, the decision making processes that underlies the choice to engage in risky sex is not well characterized. A fronto-parietal-limbic network is known to be involved the assignment of value to immediate and delayed outcomes in delayed discounting tasks that measure how delayed rewards lose their value when delayed (McClure et al., 2004, 2007), and stimulant-dependent participants differentially recruit this network (Monterosso et al., 2007). The recently developed sexual discounting task (Johnson & Bruner, 2012, 2013) is a measure of HIV risk that is similar to a monetary discounting task, but assesses how the decision to engage in hypothetical risky sex changes as a function of the delay to condom availability, thereby obtaining a safe-sex discount rate. We have collected preliminary data showing that safe-sex discount rates are much higher in cocaine-dependent participants than non-dependent controls, as well as in males compared to females. The proposed research will help illuminate the poorly understood decision-making processes about gender and risky sex in stimulant-dependent participants and controls by directly comparing BOLD response using fMRI in fronto-parietal-limbic valuation networks during decisions about engaging in risky sex and delayed money. Examining interaction effects between these variables will allow us to determine whether the effect of stimulant dependence on safe-sex discount rates depends on gender (or vice versa), or if these factors affect decision- making independently. We propose to compare discount rates and associated brain activation of the sex discounting and monetary discounting tasks in cocaine dependence vs controls (Specific Aim 1) and between males and females (Specific Aim 2), and the interaction between these. We will measure BOLD response using fMRI while participants make choices between immediate risky sex and safer sex that is delayed by various durations of time. We will also explore the role of risky sexual practices and race in an Exploratory Aim. Together, these aims will address the decision-making processes underlying risky sexual behavior in both stimulant users and non-stimulant users, and could inform future research to predict, prevent, and treat risky sexual behavior in both stimulant-dependent and non-dependent populations.

? DESCRIPTION (provided by applicant): Nearly 18% of United States adults meet criteria for alcohol dependence sometime in their lifetime, with only 24% of those individuals ever receiving any treatment for their disorder. Nearly 30% of people who meet criteria for alcohol abuse or dependence have considered seeking treatment, but have not done so. The pervasiveness of alcohol dependence indicates a need for continued development of high-impact treatments that are both effective and easily disseminated to a broad population. Contingency management, or the delivery of monetary incentives contingent on verified abstinence, is an effective treatment for drug and alcohol abuse. However, the cost of incentive payments for abstinence and technological barriers to accurate, frequent biochemical verification of alcohol abstinence limit the use of this technique for the treatment of alcohol dependence. Deposit contracts, where the participant contributes to their own incentive fund up front, have been shown to reduce or eliminate incentive costs in similar treatments. Also, a breathalyzer has recently been developed with technological features that make it ideally suited for use in a contingency management intervention. This breathalyzer has the capacity to remotely verify abstinence from alcohol and contains a number of features to verify the identity of the user and prevent tampering. In the present application, we propose to use deposit contracts and this breathalyzer to facilitate a contingency-management intervention to reduce alcohol use that requires no in-person contact between the participants and the study staff during the intervention phase and is cost effective. To this end, we propose two specific aims. First, we will determine the feasibility of remotely-delivered contingency management trial to reduce alcohol use by using technological advances to overcome barriers in treatment delivery. We will conduct a randomized, controlled two-group feasibility study with a Contingent and Noncontingent group. The Contingent group will provide a deposit and then receive nearly immediate monetary payments over the internet each day they remotely provide negative breathalyzer samples. The Noncontingent group will also provide a deposit and receive payments each day they successfully provide samples independent of the alcohol content of those samples. Our first Specific Aim is to determine whether the contingency management intervention reduces alcohol use in the Contingent group to a greater extent than the Noncontingent group. In our second Specific Aim, we will assess participant ratings of acceptability and usefulness of these novel technologies. Poor ratings of acceptability or usefulness may suggest challenges of compliance and further dissemination. As potential treatment vehicles, it is important to assess whether the various technological tools and procedures used in this feasibility trial are viewed as effective and acceptable among individuals who are interested in reducing or ceasing their alcohol use. Together these specific aims will allow us to determine if remote, verified alcohol monitoring combined with deposit contracts is an effective treatment for alcohol dependence that is well accepted by participants.

PROJECT SUMMARY/ABSTRACT In 2009, the Food and Drug Administration (FDA) was granted authority, to reduce, but not eliminate, nicotine in tobacco products if it benefited the public health. With this authority, the FDA could test the speculation that the dose of nicotine could be reduced to a level that would not result in the addictive process usually observed with conventional cigarettes. In the proposed project, we will use behavioral economic methods to examine consumption of reduced-nicotine cigarettes within the context of the larger tobacco marketplace. These experiments will assess the abuse liability of reduced-nicotine compared to conventional cigarettes and the impact of introducing reduced-nicotine cigarettes into the larger marketplace either in addition to or instead of conventional cigarettes and address two specific aims. Specific Aim 1 is to examine the effect of nicotine concentration in tobacco and resulting plasma nicotine on laboratory behavioral economic measures of demand intensity and elasticity with a within-subject design. Specific Aim 2 is to assess behavioral economic measures of demand intensity and elasticity of cigarettes and substitution by dose in the Experimental Tobacco Marketplace under 4 conditions that mimic 2 different potential regulatory environments and 2 control conditions. The Experimental Tobacco Marketplace is a method we recently developed in our laboratory that allows experimental price manipulation while simulating real-world markets featuring a wide range of available tobacco products. This novel model will permit us to prospectively identify the possible consequences of introducing low nicotine containing cigarettes into the complex tobacco market. These studies address at least three important gaps in knowledge concerning abuse liability of reduced-nicotine cigarettes: (1) How valued are reduced-nicotine cigarettes (abuse liability), (2) Would these reduced-nicotine cigarettes be preferred and substitute for conventional cigarettes in an ever more complex tobacco marketplace, and (3) Would the introduction of reduced-nicotine cigarettes into the marketplace influence the consumption of other non-combustible nicotine products.

? DESCRIPTION (provided by applicant): Nearly 18% of United States adults meet criteria for alcohol dependence sometime in their lifetime, with only 24% of those individuals ever receiving any treatment for their disorder. Nearly 30% of people who meet criteria for alcohol abuse or dependence have considered seeking treatment, but have not done so. The pervasiveness of alcohol dependence indicates a need for continued development of high-impact treatments that are both effective and easily disseminated to a broad population. Contingency management, or the delivery of monetary incentives contingent on verified abstinence, is an effective treatment for drug and alcohol abuse. However, the cost of incentive payments for abstinence and technological barriers to accurate, frequent biochemical verification of alcohol abstinence limit the use of this technique for the treatment of alcohol dependence. Deposit contracts, where the participant contributes to their own incentive fund up front, have been shown to reduce or eliminate incentive costs in similar treatments. Also, a breathalyzer has recently been developed with technological features that make it ideally suited for use in a contingency management intervention. This breathalyzer has the capacity to remotely verify abstinence from alcohol and contains a number of features to verify the identity of the user and prevent tampering. In the present application, we propose to use deposit contracts and this breathalyzer to facilitate a contingency-management intervention to reduce alcohol use that requires no in-person contact between the participants and the study staff during the intervention phase and is cost effective. To this end, we propose two specific aims. First, we will determine the feasibility of remotely-delivered contingency management trial to reduce alcohol use by using technological advances to overcome barriers in treatment delivery. We will conduct a randomized, controlled two-group feasibility study with a Contingent and Noncontingent group. The Contingent group will provide a deposit and then receive nearly immediate monetary payments over the internet each day they remotely provide negative breathalyzer samples. The Noncontingent group will also provide a deposit and receive payments each day they successfully provide samples independent of the alcohol content of those samples. Our first Specific Aim is to determine whether the contingency management intervention reduces alcohol use in the Contingent group to a greater extent than the Noncontingent group. In our second Specific Aim, we will assess participant ratings of acceptability and usefulness of these novel technologies. Poor ratings of acceptability or usefulness may suggest challenges of compliance and further dissemination. As potential treatment vehicles, it is important to assess whether the various technological tools and procedures used in this feasibility trial are viewed as effective and acceptable among individuals who are interested in reducing or ceasing their alcohol use. Together these specific aims will allow us to determine if remote, verified alcohol monitoring combined with deposit contracts is an effective treatment for alcohol dependence that is well accepted by participants.

PROJECT SUMMARY/ABSTRACT Lifetime prevalence of DSM-5 alcohol use disorder in the United States is 29%, but only 20 to 24% of people with alcohol use disorder ever seek treatment. The most prevalent reasons given for not seeking treatment relate to an inability or unwillingness (e.g., due to stigmatization) to attend traditional in-person treatment. For individuals who do receive medical treatment or care for alcohol use disorder, their first point of contact with the medical community is often for alcohol detoxification. Unfortunately, relapse following alcohol detoxification is common and few people continue utilizing treatment services after being discharged. The pervasiveness of alcohol use disorder indicates a need for continued development of high-impact treatments that are effective, acceptable to the untreated, and easily disseminated widely. Contingency management, or the delivery of monetary incentives contingent on verified abstinence, is an effective treatment for alcohol use disorder. However, costs and barriers to accurate, frequent biochemical verification of alcohol abstinence limit the widespread use of this technique for alcohol use disorder. In our preliminary data, we?ve successfully demonstrated the feasibility of remote alcohol monitoring and incentives for the reduction of alcohol use. We used technologically advanced mobile breathalyzers to verify abstinence remotely, cell phones for communication, and a reloadable debit card to deliver incentives with little delay. Our preliminary study has shown a high rate of abstinence with this model and participants gave this approach high ratings for effectiveness and acceptability. Here, we will develop this model into two treatment options ready for dissemination: 1) a stand-alone remote treatment directed toward abstinence initiation and maintenance in underserved individuals, and 2) an adjunct to existing treatment services to prevent relapse after hospital detoxification. We will also address additional gaps in knowledge in both treatment contexts: 1) what the maximally effective duration and intensity of abstinence incentives is, and 2) what the persistence of treatment effects are once incentives are discontinued. Through the use of technological advancements combined in a novel way with abstinence incentives, the proposed research has the potential to provide a framework for bringing effective, evidence-based treatments to a large number of individuals with alcohol use disorder who are currently underserved by existing treatment options or are unable to maintain abstinence after detoxification. Due to the extent of automation and relatively low use of research staff to execute, this treatment model is highly scalable, an important feature when addressing the large problem of untreated alcohol use disorder.