D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a translational approach.

Cue-elicited craving for alcohol is well established but extinction-based treatment to extinguish this response has generated only modest positive outcomes in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS) enhances extinction to fear cues under certain conditions. However, it remains unclear whether DCS would also accelerate extinction of cue-elicited craving for alcohol. The goal of the current study was to examine whether, compared with placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment-seeking individuals with alcohol use disorders (AUDs). Participants were administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a simulated bar environment on two occasions. The extinction procedures occurred 1 week apart and were fully integrated into outpatient treatment. Subjective craving for alcohol was the primary variable of interest. Follow-up cue reactivity sessions were conducted 1 week and 3 weeks later to ascertain persisting DCS effects. Drinking outcomes and tolerability were also examined. DCS was associated with augmented reductions in alcohol craving to alcohol cues during the first extinction session and these effects persisted through all subsequent sessions, suggesting facilitation of extinction. Participants in the DCS condition reported significant short-term reductions in drinking, although these did not persist to follow-up, and found the medication highly tolerable. These findings provide evidence that DCS enhances extinction of cue-elicited craving for alcohol in individuals with AUDs in the context of outpatient treatment. The potential clinical utility of DCS is discussed, including methodological considerations and context-dependent learning.

Validation of the Marijuana Effect Expectancy Questionnaire-Brief.

The purpose of this study was to evaluate a brief version of the Marijuana Effect Expectancy Questionnaire (MEEQ; Schafer & Brown, 1991). The original MEEQ was reduced to 6 items (MEEQ-B). Principal component analysis (PCA) was performed and two factors were identified (positive effects and negative effects) accounting for 52.3% of the variance. Internal consistencies (0.42 to 0.60) were slightly lower than those of the original MEEQ. The negative effect expectancy scale correlated with criterion variables that assess marijuana use (p ≤ .05). This measure is a helpful tool for clinicians to use when assessing youth expectancies. Replication across different samples of adjudicated youth is recommended.

Validity and Reliability of the Alcohol Expectancy Questionnaire-Adolescent, Brief.

The purpose of this study was to evaluate a brief version of the Alcohol Expectancy Questionnaire-Adolescent (AEQ-A; Brown, Christiansen, & Goldman, 1987). The original AEQ-A was reduced to seven items (called the AEQ-AB). Principal Components Analysis (PCA) was performed and two factors emerged (General Positive Effects and Potential Negative Effects) accounting for 46% of the variance. Internal consistencies are comparable to those of the original AEQ-A (0.50). Scales correlate with criterion variables such as average drinks per week and average number of drinks per heavy drinking day (p < 0.05). It is concluded that this questionnaire may be useful to clinicians providing brief assessment and intervention. Cross-validation in other samples and other settings is recommended.

Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1-year outcomes.

BACKGROUND: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts. METHODS: A 2 x 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2-week partial hospital program (n = 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n = 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited. RESULTS: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self-efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy. CONCLUSIONS: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes.

Risks associated with alcohol-positive status among adolescents in the emergency department: a matched case-control study.

OBJECTIVE: The purpose of this study was to examine alcohol use, alcohol-related problems, other risk-taking behaviors, and parental monitoring in adolescents who tested positive for alcohol in an emergency department. STUDY DESIGN: A matched case-control design was implemented for adolescents presenting to a pediatric emergency department who were screened for alcohol use. An alcohol-positive sample (N = 150) was compared with a matched alcohol-negative sample (N = 150) for alcohol use, alcohol problems, depression, smoking, risk-taking behavior, and parental monitoring. RESULTS: The alcohol-positive group reported significantly higher drinking frequency, drinking problems, prior alcohol-related injuries, and episodes of driving after drinking and riding with a drinking driver than the alcohol-negative adolescents. The same pattern was true for depressed mood, reckless behaviors, poor grades in school, and daily smoking. The parents of alcohol-positive teens reported their teens had come home intoxicated more often than parents of alcohol-negative teens. There were no differences between parent groups in monitoring of teens. CONCLUSION: Adolescents who test positive for alcohol in an emergency department are a high-risk group who meet the criteria for indicated prevention. Screening for alcohol abuse is recommended.

Concurrent versus delayed smoking cessation treatment for persons in early alcohol recovery. A pilot study.

This pilot study investigated the efficacy of initiating a smoking cessation intervention early in inpatient treatment for alcohol dependence versus shortly after an inpatient stay. Thirty-six male smokers recruited from an inpatient substance abuse treatment program were randomly assigned to begin smoking cessation either two weeks (concurrent treatment) or six weeks (delayed treatment) after admission to the substance abuse program. Smoking cessation treatment involved three sessions of individual smoking cessation treatment plus eight weeks of transdermal nicotine replacement. Significantly fewer participants began the delayed treatment than the concurrent treatment. Few participants were smoking-abstinent at follow-up, and the timing of treatment onset did not have an impact on smoking outcome. Clinical trials with larger samples may be needed to better evaluate the efficacy of concurrent versus delayed treatment and to test the efficacy of more aggressive interventions with smokers in early alcohol recovery.

Cue exposure with coping skills training and communication skills training for alcohol dependence: 6- and 12-month outcomes.

AIMS: Cue exposure treatment (CET) has shown promise in preliminary studies with alcoholics, and Communication Skills Training (CST) has been found beneficial, especially in intensive treatment programs. The aim of the present study was to investigate the effects of CET and CST in a larger controlled study when both were added to intensive treatment programs. DESIGN AND INTERVENTIONS: A 2 x 2 design investigated the effects of CET with urge coping skills training compared to a meditation-relaxation control, and CST compared to an education control when all were added to intensive treatment programs for alcoholics. SETTING: The sites were the inpatient or partial hospital substance abuse treatment programs at a private psychiatric hospital, a state-funded residential facility and a VA medical center. PARTICIPANTS: Patients diagnosed with alcohol dependence without active psychosis were eligible. MEASUREMENTS: Participants were assessed for quantity and frequency of drinking, alcohol cue-reactivity, responses to high risk simulations and urge specific coping skills. FINDINGS: Of 100 treated patients, 86% provided 6-month and 84% provided 12-month follow-up data. Patients who received either CET or CST had fewer heavy drinking days in the first 6 months than control patients. In the second 6 months, CET continued to result in fewer heavy drinking days among lapsers and interacted with CST to decrease quantity of alcohol consumed. CST resulted in fewer alcohol-related problems reported at 12 months. CET resulted in greater reductions in urge to drink in a measure of simulated high-risk situations. CET also resulted in greater reports of use of coping strategies during the follow-up, and many of the urge-specific strategies taught in CET were associated with reduced drinking. CONCLUSIONS: Both CET and CST continue to show promise as elements of comprehensive alcohol treatment programs. Limitations and directions for future research are discussed.

Olanzapine reduces urge to drink after drinking cues and a priming dose of alcohol.

RATIONALE: Haloperidol, a D2 antagonist, has been shown to moderate the effects of alcohol consumption on craving. OBJECTIVE: The present study was designed to determine whether a single 5-mg dose of olanzapine (a D2/5-HT2 antagonist) would influence responses to alcohol cues or an alcohol challenge. It was hypothesized that olanzapine would attenuate cue-elicited urge to drink, attenuate the effects of alcohol consumption on urge to drink, and reduce the rewarding effects of alcohol. METHODS: To test these hypotheses, 26 heavy social drinkers were randomized to receive either 5 mg olanzapine or placebo approximately 8 h before each of two experimental sessions. Participants consumed a moderate dose of alcohol in one experimental session and a non-alcohol control beverage in another session. RESULTS: Results indicated that mere exposure to alcohol cues and consumption of alcohol increased urge to drink and that olanzapine attenuated these effects. Results also indicated that alcohol increased subjective stimulation and high while olanzapine did not moderate these effects. CONCLUSIONS: These results suggest that olanzapine did not influence the rewarding effects of alcohol but did attenuate the effects of alcohol cues and an alcohol challenge on urge to drink.

Predictors of compliance with naltrexone among alcoholics.

OBJECTIVE: Naltrexone has been found to be an effective adjunct to treatment to reduce the rate of drinking among alcoholics. However, adherence to the medication has been of considerable concern; the high rates of noncompliance with the medication limits the benefits that could potentially be realized from this pharmacotherapy. Knowledge of predictors of noncompliance could result in interventions targeted at these variables. METHOD: Participants were 128 alcohol-dependent patients who participated in a clinical placebo-controlled trial of naltrexone. Upon discharge from a 1- to 2-week partial hospital program, patients were randomly placed into 12 weeks of naltrexone (50 mg/day) or placebo (n = 64 per condition). Patients met with a physician and a research assistant weekly for 4 weeks then biweekly for 8 weeks. RESULTS: Compliance (number of days taking medication) was not predicted by demographic or pretreatment alcohol use variables. Number and severity of side effects in the first week, particularly nausea and fatigue, predicted early termination. Compliance was not predicted by commitment to abstinence or self-efficacy about abstinence, but was greater among patients who believed more strongly that the medication would help them stay sober. Compliance was not predicted by general level of urge to drink during the first week on medication but compliance was greater among those with a higher urge to drink in response to alcohol stimuli in the laboratory. CONCLUSIONS: Implications for approaches to increase compliance include reducing side effects and increasing patients' beliefs in the efficacy of naltrexone.

Toward bridging the gap between biological, psychobiological and psychosocial models of alcohol craving.

Urge to drink ("craving") has been a central focus of many theories and treatments, but some researchers question the importance of urges during recovery. Several studies assessed reactions to the presence of beverage alcohol (cue-reactivity) or to simulated high-risk situations (role plays). Higher urges in response to role plays predicted more drinking during the 6 months after treatment. However, urges in response to beverage cues were inconsistently predictive of outcome while measures of awareness or attention to cues predicted less drinking. Urge to drink might reflect a conflict between motivation to drink and awareness of danger. Whether urges predict increased risk of drinking should be a function of factors that affect motivation to drink, awareness of risk and effectiveness of coping. Cue-reactivity assessment has recently been used to bridge the gap between psychosocial and biomedical approaches in several ways: (1) salivation to cues predicts increased drinking independent of urge or attention, showing the value of including both physiological and psychosocial measures; (2) naltrexone has been shown to decrease cue-elicited urge to drink, illustrating the value of this assessment methodology for medications evaluation and (3) pre-pulse inhibition of startle response is being used to investigate the role of dopaminergic pathways in cue-elicited urge. Thus, this laboratory based program of research has the potential to add to knowledge of both biomedical and psychosocial mechanisms involved in urge and relapse, leading to greater integration of models.

Screening adolescents for problem drinking: performance of brief screens against DSM-IV alcohol diagnoses.

OBJECTIVE: The performance of three brief screens, the CAGE, TWEAK and Alcohol Use Disorders Identification Test (AUDIT), was evaluated against a DSM-IV diagnosis of alcohol abuse or dependence in an adolescent sample. METHOD: Adolescents (13-19 years old) who presented to an emergency department for treatment of an injury, and who tested negative for blood alcohol concentration at time of admission, were administered a structured diagnostic interview and modified versions of the CAGE, TWEAK and AUDIT. RESULTS: Of the 415 adolescents for whom complete data were available, 18% met criteria for a DSM-IV alcohol use disorder according to the Diagnostic Interview Schedule for Children (version 2.3). Teens who reported alcohol use in the last year (n = 261, 58% male, 71% white) were included in analyses that compared the performance of the three screening instruments. Receiver Operating Characteristic analysis indicated that the AUDIT demonstrated the best performance across the range of its cut-scores, with optimal performance at a cut-score of 4. The TWEAK performed optimally at a cut-score of 2 and the CAGE at a cut-score of 1. CONCLUSIONS: Routine alcohol screening among adolescents seen in a hospital setting is indicated. Two important directions for future research include the identification of adolescent-specific alcohol screening items, and the validation of an adolescent-specific definition of problem drinking that addresses limitations of DSM-IV alcohol diagnoses when applied to adolescents.

Brief coping skills treatment for cocaine abuse: 12-month substance use outcomes.

Patients (N = 108) in a study of cocaine-specific coping skills training (CST), which was found to reduce cocaine use during a 3-month follow-up, were followed for an additional 9 months. CST involved coping skills training in the context of high-risk situations. Control treatment used meditation-relaxation. Both were added to comprehensive private substance abuse treatment. Patients in CST who relapsed had significantly fewer cocaine use days than did the control group during the first 6 months, then both conditions did equally well. Patients in CST also drank alcohol more frequently in the last 6 months than did contrast patients but did not differ in heavy drinking days. For cocaine use outcomes, no interaction of treatment was found with gender, education, route of administration, drug use severity, sociopathy, or depression. Implications include the need to investigate different lengths and combinations of treatment.

The relationship between anxiety levels and outcome of cocaine abuse treatment.

Although a number of studies have examined the comorbidity of anxiety disorders and substance use disorders, much less is known about the impact of anxiety symptoms on substance use and on substance abuse treatment outcome. In the current study, we examined how self-reported anxiety levels, as measured by the Spielberger State-Trait Anxiety Inventory, were related to cocaine use variables and patterns following substance abuse treatment. There were 108 patients in substance abuse treatment who met DSM-III-R diagnostic criteria for cocaine abuse or dependence who completed an assessment battery at pretreatment, posttreatment, and 3-month follow-up. State anxiety scores significantly declined from pre- to posttreatment and remained stable into the 3-month follow-up period regardless of relapse status. Trait anxiety was correlated positively with negative consequences due to cocaine use and negatively correlated with days in treatment. State and trait anxiety both were correlated positively with the Alcohol Composite Index of the Addiction Severity Index (ASI). These findings suggest that elevated anxiety scores at pretreatment subside with time, do not require clinical management of associated anxiety symptoms, and may be a temporary by-product of experiencing negative consequences due to recent cocaine use.

Effects of nicotine deprivation on alcohol-related information processing and drinking behavior.

This study examined the influence of smoking cues and nicotine deprivation on responses to alcohol among hazardous drinkers. Fifty-six daily smoking, hazardous drinkers were exposed to either smoking cues or control cues after either 6 hr of nicotine deprivation or no deprivation. Urges to drink alcohol, alcohol-related cognitive processing, and alcohol consumption were assessed after cue exposure. Results indicated that nicotine deprivation increased urges to drink, the accessibility of alcohol outcome expectancies, and the volume of alcohol consumed. There was little influence of the smoking cue manipulation on these processes. Implications for understanding the mechanisms underlying alcohol-tobacco interactions are discussed.

Smoking and drinking among alcoholics in treatment: cross-sectional and longitudinal relationships.

OBJECTIVE: The relationship between tobacco dependence and alcohol dependence has received considerable scrutiny in the past few years. The present study of alcoholics in treatment for alcoholism extended previous work by investigating the cross-sectional and longitudinal relationships between drinking and smoking variables. METHOD: Male and female alcoholics (N = 116) completed a standard assessment of smoking and drinking pretreatment followed by a laboratory assessment of reactivity to alcohol cues. Participants' drinking and smoking were evaluated again 6 months following treatment. RESULTS: (1) Pretreatment tobacco dependence, pretreatment alcohol dependence, urge to smoke and urge to drink were positively correlated; (2) smoking rates and drinking rates were not correlated either before or following treatment; (3) pretreatment smoking history did not predict posttreatment drinking; (4) the rate of smoking declined following treatment for alcoholism for 45% of the smoking patients who completed a 6-month follow-up, independent of relapse status; and (5) relapsers who smoked more heavily also drank less frequently during follow up. CONCLUSIONS: Consistent but modest cross-sectional relationships between drinking and smoking variables before alcohol treatment decrease after treatment for alcohol dependence. A spontaneous improvement in smoking rate occurs in many (45%), particularly among those who smoked more heavily pretreatment and thus benefit most by the reduction. Directions for future research are discussed.

Naltrexone's effects on reactivity to alcohol cues among alcoholic men.

The mechanisms of naltrexone's effects on urges to drink during abstinence are unclear. Naltrexone may suppress either urges to drink specifically or appetitive responses in general. The effects of naltrexone on cue reactivity to alcoholic and sweet nonalcoholic beverages were investigated. Alcohol-dependent men (N = 53) in treatment received naltrexone (50 mg) or placebo. Four hours later, they received baseline assessment, exposure to fruit juice, and exposure to their usual alcoholic beverage in 3-min trials. Naltrexone reduced urge to drink and self-reported attention to the alcohol cues, not at the initial exposure but after repeated exposures to alcohol cues. Naltrexone reduced negative affect across baseline and alcohol trials. No effects of naltrexone on responses to the nonalcoholic appetitive beverage cues were found, suggesting that general appetite suppression does not mediate the effects of naltrexone on urges.

Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department.

This study evaluated the use of a brief motivational interview (MI) to reduce alcohol-related consequences and use among adolescents treated in an emergency room (ER) following an alcohol-related event. Patients aged 18 to 19 years (N = 94) were randomly assigned to receive either MI or standard care (SC). Assessment and intervention were conducted in the ER during or after the patient's treatment. Follow-up assessments showed that patients who received the MI had a significantly lower incidence of drinking and driving, traffic violations, alcohol-related injuries, and alcohol-related problems than patients who received SC. Both conditions showed reduced alcohol consumption. The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking, beyond what was produced by the precipitating event plus SC alone.

Cue exposure treatment for smoking relapse prevention: a controlled clinical trial.

AIMS: In an additive design, test the efficacy of cue exposure treatment for smoking relapse prevention as an adjunct to current standard cognitive behavioral and pharmacological treatments. DESIGN: Randomized, controlled clinical trial. SETTING: Outpatient behavioral medicine clinic. PARTICIPANTS: One hundred and twenty-nine cigarette smokers recruited through newspaper advertisements. INTERVENTION: After receiving an initial counseling session for cessation and setting a quit day, 129 smokers were randomly assigned to one of four relapse prevention treatment conditions: (1) brief cognitive behavioral; (2) cognitive behavioral and nicorette gum; (3) cognitive behavioral and cue exposure; and (4) cognitive behavioral and cue exposure with nicorette gum. All smokers met individually with their counselor for six RP sessions. MEASURES: Seven-day, point-prevalence abstinence rates (CO verified) taken at 1, 3, 6 and 12-months post-treatment and time to first slip. FINDINGS: All manipulation checks and process measures suggested that the treatments were delivered as intended. There were no significant differences between conditions in point-prevalence abstinence rates or in time to first slip. CONCLUSIONS: These results call into question the utility of cue exposure treatment for smoking relapse prevention.

Naltrexone's effect on cue-elicited craving among alcoholics in treatment.

BACKGROUND: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high-risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory-based, cue-elicited urge to drink among abstinent alcoholics in treatment. METHODS: Alcohol-dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After approximately 1 week on medication, all received cue reactivity assessment. RESULTS: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue-elicited decreases in heart rate were not affected by the medication. CONCLUSIONS: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments.