Based on the 2003-2004 National Survey on Drug Use and Health, 1.5 million youth aged 12-17 years (6.1% of youth in that age range) needed treatment for alcohol abuse, and alcohol is the primary drug reported by 19% of the adolescent treatment population. Recent intervention research on adolescent alcohol abuse has focused primarily on school-based, community, or ER populations. Although new outpatient family-based and contingency-management (CM) interventions for adolescent marijuana abuse have been developed, not one of them specifically targets adolescent primary alcohol users. We could find no published outpatient randomized trial specifically targeting alcohol abuse in adolescents. Thus, little is known about how to most effectively intervene with primary adolescent alcohol abuse and dependence in an outpatient setting. Our goal is to adapt our family-based CM treatment to target primary adolescent alcohol abuse and dependence. Specific Aim 1 is to provide a preliminary demonstration of the efficacy of a family based CM intervention to treat adolescent alcohol abuse and dependence. CM components include 1) an incentive program to enhance the adolescent's engagement in the treatment process and engender alcohol abstinence by providing positive reinforcement for documented abstinence via breathalyzers administered by parents regularly at home, self and parent report, and clinic-based urine drug testing; and 2) a parent management training program to enhance and maintain the positive effects of the incentive program by teaching parents how to effectively use contingency management in the home environment to motivate their adolescent to achieve abstinence and improve their behavior in other domains. 
 
A randomized trial will determine whether the CM intervention enhances outcomes when added to a standard individual cognitive behavioral therapy. Specific Aim 2 is to determine whether and how treatment interventions modify parental and adolescent risk and protective factors using observational and laboratory measures (parenting practices, family functioning, risk taking, delay discounting, and child and parent psychopathology) and to determine whether these factors are associated with outcomes over time. Findings will extend the scientific evidence for CM and support the ability of parents to implement CM at home. Findings that support the CM model's efficacy will make a significant contribution to research on the treatment of adolescent alcohol abuse, which has lagged behind research on adult substance abuse and on adolescent illicit drug use. Future projects will include isolation of active treatment components, dissemination to community clinics, and cost-effectiveness studies.

More US residents are dependent on marijuana than on any other illicit drug, and the number enrolled in treatment for marijuana continues to increase such that it is now comparable to that for cocaine and heroin. This application seeks to advance our overarching goal to develop and disseminate cost-effective treatments for marijuana dependence that can address this growing problem. Our previous research suggests that an intervention comprising motivational enhancement, cognitive-behavioral, and contingency-management components (MET/CBT/CM) produces greater rates of successful and durable outcomes than has been demonstrated previously. However, three issues relevant to its efficacy and eventual dissemination must be confronted. First, the outcomes achieved can only be characterized as modest; many individuals do not respond to the treatment and relapse rates remain problematic. Second, access is limited by the availability of trained providers. Third, the cost of delivering the treatment is higher than more traditional outpatient interventions. To address these issues, Specific Aim 1 is to develop and test a computer-assisted version of MET/CBT/CM. Computerized treatments have the potential to increase overall effectiveness of treatment services by increasing availability of and access to potent treatments, and by applying innovative technology to enhance outcomes. During Year 1, the intervention will be developed and pilot tested. An interactive program that showed promise in our previous trial for opioid dependence will be modified and enhanced to deliver individualized MET/CBT/CM using effective computer learning technologies. These technologies and access to the MET/CBT/CM program made available via the Internet between treatment sessions and after treatment ends have the potential to promote better learning and more use of coping skills, which in turn can improve outcomes. During Years 2-4 a randomized trial will provide an initial efficacy test of cMET/CBT/CM by comparing it with a brief treatment (MET) and with therapist-delivered MET/CBT/CM. Specific Aim 2 is to learn more about how behavioral treatments like MET/CBT/CM work by focusing on two putative mechanisms of action examined in prior trials: self-efficacy/coping skills and impulsivity/delay discounting. The experimental design will provide a unique opportunity to explore such mechanisms in a novel context—where the therapist is vs. is not a prominent part of the treatment. The proposed project will address the objectives of NIDA's Behavioral and Integrative Treatment Development Program by providing research on technology-assisted treatment that attempts to make treatment delivery less complex, easier to access, and less costly - while retaining or improving its effectiveness. Findings will inform future studies designed to refine the technology and how it is applied; conduct more definitive effectiveness testing; test generality to other populations including adolescents; and to further advance translation to community settings.

Based on the 2003-2004 National Survey on Drug Use and Health, 1.5 million youth aged 12-17 years (6.1% of youth in that age range) needed treatment for alcohol abuse, and alcohol is the primary drug reported by 19% of the adolescent treatment population. Recent intervention research on adolescent alcohol abuse has focused primarily on school-based, community, or ER populations. Although new outpatient family-based and contingency-management (CM) interventions for adolescent marijuana abuse have been developed, not one of them specifically targets adolescent primary alcohol users. We could find no published outpatient randomized trial specifically targeting alcohol abuse in adolescents. Thus, little is known about how to most effectively intervene with primary adolescent alcohol abuse and dependence in an outpatient setting. Our goal is to adapt our family-based CM treatment to target primary adolescent alcohol abuse and dependence. Specific Aim 1 is to provide a preliminary demonstration of the efficacy of a family based CM intervention to treat adolescent alcohol abuse and dependence. CM components include 1) an incentive program to enhance the adolescent's engagement in the treatment process and engender alcohol abstinence by providing positive reinforcement for documented abstinence via breathalyzers administered by parents regularly at home, self and parent report, and clinic-based urine drug testing; and 2) a parent management training program to enhance and maintain the positive effects of the incentive program by teaching parents how to effectively use contingency management in the home environment to motivate their adolescent to achieve abstinence and improve their behavior in other domains. 
 
A randomized trial will determine whether the CM intervention enhances outcomes when added to a standard individual cognitive behavioral therapy. Specific Aim 2 is to determine whether and how treatment interventions modify parental and adolescent risk and protective factors using observational and laboratory measures (parenting practices, family functioning, risk taking, delay discounting, and child and parent psychopathology) and to determine whether these factors are associated with outcomes over time. Findings will extend the scientific evidence for CM and support the ability of parents to implement CM at home. Findings that support the CM model's efficacy will make a significant contribution to research on the treatment of adolescent alcohol abuse, which has lagged behind research on adult substance abuse and on adolescent illicit drug use. Future projects will include isolation of active treatment components, dissemination to community clinics, and cost-effectiveness studies.

In this research, we will continue our study of computerized treatment. In a prior trial, computer-delivered Community Reinforcement Approach (CRA) with contingency management (CM) was as effective as therapist-delivered CRA with CM. The design of that study, however, did not indicate whether the computer-delivered CRA produced increases in therapeutic outcomes over that produced by the CM procedures alone. Thus, we will propose to isolate the contribution of the computerized treatment to therapeutic outcomes. Second, we will examine the efficacy of a component of CRA, therapist-delivered facilitation of treatment goals and outreach services (FOS) that cannot be computerized. The efficacy of FOS has not been previously examined. In the process, we will address the infrequently acknowledged problem of rural opioid dependence. The aim of this project is to address this serious public health concern by being one of only three outpatient clinics providing pharmacotherapies for opioid dependence in the State of Arkansas.

Understanding drug dependence requires an understanding of the factors that render drug taking preeminent among otherwise powerful reinforcers (e.g., work, family, & health). Discussed in this manner, drug dependence is a matter of understanding reinforcer interactions.  Behavioral economics provides a new conceptual system to understand reinforcer interactions and choice. In this MERIT Award continuation, we propose to use this behavioral economic approach to drug choice to address three purposes We will stringently test a new behavioral economic theory of relative reinforcing efficacy that we developed in the prior grant period. We have proposed an empirically derived theory of reinforcing efficacy that can account for data where the typical measures of reinforcing efficacy are concordant and where they are not. In this regard, our theory appears to be a more general account. However, a more stringent test would be to discern within subject whether the behavioral economic theory could account for concordant and discordant data.

The discounting of delayed reinforcers among the drug dependent has been increasingly studied. The results of that research are consistent and reflect an important dimension of drug dependence. Specifically, these studies have shown that drug-dependent individuals discount money more than matched controls. Moreover, drug-dependent participants discount their drug of dependence more than they discount money. Ex-dependent or recently abstinent drug users discount money either at a rate intermediate between current drug-dependent individuals and matched controls, or at a rate that approximates discounting of the matched controls. Furthermore, reinforcing abstinence has been shown to decrease the discounting of money and cigarettes in the drug dependent. Overall, these studies suggest that drug-dependent individuals discount more than controls and the excessive discounting among the drug dependent may be a reversible effect of drug use. In this grant, we are continuing this productive research by addressing three specific aims. The first specific aim is to examine whether drug-dependent individuals with co-morbidity discount delayed reinforcers more than individuals without that co-morbidity. The second specific aim is to examine new discounting procedures. The third specific aim is to examine conditions that will modulate the degree of discounting.
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Our research on the marijuana withdrawal syndrome has primarily involved human laboratory studies documenting the reliability, validity, time course, and pharmacological specificity of the syndrome.  Most recently, this project has engaged in direct comparisons of marijuana and tobacco withdrawal, as well as withdrawal that follows simultaneous cessation of tobacco and marijuana among those who use both substances regularly. Data from these studies indicate great similarity between these two withdrawal syndromes and an interesting, non-additive effect of withdrawal from both substances simultaneously. This project has also used survey methodology to document characteristics and rates of withdrawal symptoms among clinical samples of adults and adolescents seeking treatment for marijuana abuse or dependence.  An additional telephone survey study has been comparing tobacco and marijuana withdrawal among adults who have made recent cessation attempts. Planned studies in this area will involve more clinically relevant experiments that involve adults and adolescents seeking treatment for marijuana dependence.  Future projects will also follow-up on the multiple substance withdrawal phenomenon and the development of behavioral or pharmacological interventions that target marijuana withdrawal.

Marijuana remains the most prevalent illicit substance used by adolescents and the number of adolescents receiving treatment for marijuana abuse more than tripled during the last decade. A small number of clinical trials suggest that family-based and individual interventions have efficacy for treating adolescent substance abuse. However, even with these interventions most adolescents fail to reduce their substance use substantially, thus, there remains much room for improvement of treatment services. The overarching goal of this project is to develop and test novel behavioral treatments to enhance treatment outcome in this important treatment population, and in so doing, learn more about mechanisms of change that have broader implications for addiction science. In our initial Stage IB project "Behavioral Treatment for Adolescent Marijuana Abuse", we created, manualized, and pilot tested a unique contingency-management (CM) intervention that combined abstinence-based voucher incentives with contingency management training for parents. A small randomized, clinical trial provided encouraging results. When added to a commonly used cognitive-behavior therapy, CM improved rates of sustained abstinence during treatment. Adolescents receiving this intervention were less likely to relapse over the 9-month follow-up period, however this finding was not as robust as the observed during treatment effects, most likely due to the small sample size and associated low power to detect effects. Despite strong indicators of the efficacy of this CM intervention, there remained room for improvement in increasing rates of treatment response and reducing rates of relapse. Hypothesized mediators and moderators of change indicated that changes in parenting had direct effects on post-treatment marijuana abstinence outcomes, and that abstinence early in treatment was a robust predictor of the CM treatment effect. This proposal will systematically replicate and extend these findings. A Stage II trial will compare three treatment conditions: (1) cognitive behavior therapy (CBT only); (2) CBT plus CM; and (3) CBT plus an enhanced CM model targeting increased early abstinence rates, parenting skills, and maintenance of effects. Replicating the initial demonstration of the positive effects of CM will extend the scientific evidence for use of CM to increase treatment efficacy for substance-abusing adolescents. Testing an enhanced CM model will determine if modifications that are consistent with the underlying behavioral principles and empiricism supporting CM interventions can result in improved outcomes. Last, assessment of potential mechanisms of action, particularly parenting, adolescent psychopathology and impulsivity, will provide scientific information directly relevant to future development of more effective intervention and prevention models of adolescent substance abuse, and will inform us about fundamental mechanisms operating in drug-dependence.

This is a research study that examines the behavioral effects of common medications, including sedatives and stimulants, in healthy participants. Volunteers between the ages of 18 and 70 years will participate for about 6-10 weeks, attending study sessions up to five days (Monday through Friday) per week for about 4-1/2 hours per day. This study is conducted at the General Clinical Research Center (GCRC) on the 6th floor of the Central Arkansas Veterans Healthcare System (CAVHS). Subjects are paid for their participation.

These series of studies investigate the effects of common medications in methadone-maintained individuals, examining their ability to distinguish between two drugs as well as to compare the effects of other drugs to these two drugs. This study is conducted at the General Clinical Research Center (GCRC) on the 6th floor of the Central Arkansas Veterans Healthcare System (CAVHS). Volunteers will be recruited for this study from the UAMS Substance Abuse Treatment Clinic and will participate on an outpatient basis. Subjects are maintained on their stable dose of methadone through the methadone clinic and will ingest their medication prior to attending study sessions. Subjects are paid for their participation.

This 14-wk, placebo-controlled, double-blind, randomized clinical trial examines the clinical efficacy of disulfiram in reducing cocaine use in opioid-dependent cocaine abusers maintained on methadone and receiving Cognitive Behavioral Therapy. Dually opioid- and cocaine-dependent volunteers participate on an outpatient basis and are stabilized on methadone and assigned to receive a dose of disulfiram or placebo. Participants attend clinic six days per week to receive medication and complete research tasks. At the end of the trial, participants no longer receive disulfiram (or placebo) and are either transferred to a local methadone program, if eligible, or tapered off methadone over a 4- to 6-week period. Individuals participate at no cost to them.

This 12-wk, randomized, placebo-controlled, double-blind clinical trial examines the clinical efficacy of the antidepressant sertraline alone or augmented with gabapentin, prescribed for nerve pain as well as seizures in preventing relapse in depressed, recently abstinent cocaine dependent individuals. Participants first reside for 2 weeks at the Recovery Centers of Arkansas to establish abstinence and be stabilized on the medications. Then they transfer to an outpatient treatment research program for 10 weeks, during which they attend clinic at least 3 days per week in order to receive medications, receive individual psychotherapy and complete research tasks. At the end of 12 weeks, participants are tapered off their medications and referred to an area program for further treatment. Individuals participate at not cost to them. In addition, during the outpatient portion of the study, individuals can earn up to $250 for attending scheduled appointments and returning medication blister packs.

The primary purpose of this research is to examine the discounting of negative outcomes by cigarette smokers experiencing nicotine withdrawal. Given that some theories posit negative outcomes of withdrawal as a significant factor in the maintenance of cigarette smoking, the discounting of negative outcomes during withdrawal would appear to be important. Cigarette smokers participate in temporal and probability discounting procedures during both nicotine satiation (regular smoking) and acute nicotine withdrawal (24-hour abstinence).

The primary purpose of this research is to determine if discounting due to interpersonal discounting results in the same profile of results for discounting due to temporal distance. Participants are asked to rate the subjective closeness (interpersonal distance) of various persons in their lives. Participants then take part in an interpersonal discounting procedure modeled on temporal discounting studies; subjective closeness is equated to the temporal distance dimension. Participants must choose between a hypothetical outcome for the self and a hypothetical outcome for the other. Interpersonal discounting that is hyperbolic in shape, with Magnitude and Sign Effects, would replicate findings from temporal discounting research, indicating a possible commonality between the two.
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