Faculty Bibliography

BACKGROUND: Attentional bias (i.e., differences in reaction time between drug and neutral cues) has been associated with a variety of drug-use behaviors (e.g., craving, abstinence). Reduction of bias may ultimately reduce use. OBJECTIVE: The current study examined whether attentional bias modification therapy (ABMT) reduced the frequency of drug use behaviors in individuals with cocaine use disorder (CUD). METHOD: Participants (n = 37) were randomly assigned to ABMT or control therapy, which systematically varied how frequently probes replaced neutral (ABMT = 100%; control therapy = 50%) relative to drug stimuli. Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks. Clinical assessments occurred at baseline, post-intervention, 2 weeks and 3 months posttreatment. RESULTS: There were no baseline differences between groups on drug-use behaviors or other clinical measures. Contrary to predictions, both groups exhibited slower rather than faster reaction times for cocaine stimuli (p = 0.005) at baseline, with no relationship between bias and baseline measures of drug-use behavior. CONCLUSIONS: ABMT was not more effective than our control therapy at reducing attentional bias, reducing craving or changing other drug use behaviors. Current results suggest additional replication studies are needed to assess ABMT's efficacy in reducing drug-use behaviors in CUD.

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Excessive alcohol consumption is one of the most important lifestyle factors affecting the disease burden in the Western world. The results of treatment in daily practice are modest at best. The aim of the RESCueH programme is to develop and evaluate methods, which are as practice-near as possible, and therefore can be implemented quickly and easily in everyday clinical practice. It is the first clinical alcohol programme to be transatlantic in scope, with implementation in treatment centers located in Denmark, Germany and the US. The RESCueH programme comprises 5 randomized controlled trials, and the studies can be expected to result in (1) more patients starting treatment in specialized outpatient clinics, (2) a greater number of elderly patients being treated, (3) increased patient motivation for treatment and thus improved adherence, (4) more patients with stable positive outcomes after treatment and (5) fewer patients relapsing into harmful drinking. The aim of this paper is to discuss the rationale for the RESCueH programme, to present the studies and expected results.

BACKGROUND: The proportion of 60+ years with excessive alcohol intake varies in western countries between 6-16 % among men and 2-7 % among women. Specific events related to aging (e.g. loss of job, physical and mental capacity, or spouse) may contribute to onset or continuation of alcohol use disorders (AUD). We present the rationale and design of a multisite, multinational AUD treatment study for subjects aged 60+ years. METHODS/DESIGN: 1,000 subjects seeking treatment for AUD according to DSM-5 in outpatient clinics in Denmark, Germany, and New Mexico (USA) are invited to participate in a RCT. Participants are randomly assigned to four sessions of Motivational Enhancement Treatment (MET) or to MET plus an add-on with eight sessions based on the Community Reinforcement Approach (CRA), which include a new module targeting specific problems of older adults. A series of assessment instruments is applied, including the Form-90, Alcohol Dependence Scale, Penn Alcohol Craving Scale, Brief Symptom Inventory and WHO Quality of Life. Enrolment will be completed by April 2016 and data collection by April 2017. The primary outcome is the proportion in each group who are abstinent or have a controlled use of alcohol six months after treatment initiation. Controlled use is defined as maximum blood alcohol content not exceeding 0.05 % during the last month. Total abstinence is a secondary outcome, together with quality of life andcompliance with treatment. DISCUSSION: The study will provide new knowledge about brief treatment of AUD for older subjects. As the treatment is manualized and applied in routine treatment facilities, barriers for implementation in the health care system are relatively low. Finally, as the study is being conducted in three different countries it will also provide significant insight into the possible interaction of service system differences and related patient characteristics in predictionof treatment outcome. TRIAL REGISTRATION: Clinical Trials.gov NCT02084173 , March 7, 2014.

Most U.S. healthcare professionals encourage mutual-help group involvement as an adjunct to treatment or aftercare for individuals with substance use disorders, yet there are multiple challenges in engaging in these community groups. Dually diagnosed individuals (DDIs) may face additional challenges in affiliating with mutual-help groups. Twelve-step facilitation for DDIs (TSF-DD), a manualized treatment to facilitate mutual-help group involvement, was developed to help patients engage in Double Trouble in Recovery (DTR), a mutual-help group tailored to DDIs. Given the promising role that TSF-DD and DTR may have for increasing abstinence while managing psychiatric symptoms, the aim of the current study was to systematically examine reasons for TSF-DD and DTR attendance from the perspective of DDIs using focus group data. Participants were a subset (n = 15) of individuals diagnosed with an alcohol use disorder as well as a major depressive, bipolar, or psychotic disorder who participated in a parent study testing the efficacy of TSF-DD for increasing mutual-help group involvement and reducing alcohol use. Analyses of focus group data revealed that participants construed DTR and TSF-DD as helpful tools in the understanding and management of their disorders. Relative to other mutual-help groups in which participants reported feeling ostracized because of their dual diagnoses, participants reported that it was beneficial to learn about dual disorders in a safe and accepting environment. Participants also expressed aspects that they disliked. Results from this study yield helpful empirical recommendations to healthcare professionals seeking to increase DDIs' participation in DTR or other mutual-help groups.

Background: ED-based SBIRT for alcohol and drug use has the potential to affect public health greatly. Time and resource constraints limit implementation. Objectives: We aimed to determine whether particular chief complaints could be used to identify patients likely to screen positive for unhealthy alcohol or drug use, thus reducing the proportion of patients needing to be screened and increasing the efficiency of SBIRT. Methods: Cross-sectional study using baseline data from NIDA CTN0047: SMART-ED, a multicenter, randomized 3-arm SBIRT trial which screened 14,972 ED patients. Free-text chief complaints were coded using a tested algorithm, then reviewed and further collapsed by multiple team members to ensure agreement. The 454 excluded patients had missing data, complaints related to alcohol or drug use, or complaints stated by <15 subjects. Positive screens were defined as AUDIT-C > 4 for men and >3 for women (alcohol) and DAST >3 (drugs) - to detect the spectrum of unhealthy alcohol or drug use (from at-risk to dependence). We rank-ordered the chief complaints by their (Figure presented) sensitivity and positive predictive value using two strategies: 1) to minimize the number of chief complaints and 2) to assess the fewest number of ED patients. Our goal was to identify 75% of ED patients having positive assessments using these strategies. Results: The screening assessments were positive in 5,805/14,561 (39.9%) for alcohol and 2,454/14,494 (16.9%) for drugs. We collapsed the free-text chief complaints into 50 usable categories. To identify 75% of all ED patients having positive assessments using the first strategy would require including 19 chief complaints for alcohol screening and 20 chief complaints for drug screening. Adapting the second strategy, we would need to screen at least 71% and 68% of all ED patients for alcohol and drugs respectively to identify 75% of those having positive assessments. (See Table 47 and Figure 47.) Conclusion: In this multi-ED study, unhealthy alcohol and drug use was exceptionally prevalent. Using chief complaints did not significantly improve the efficiency of SBIRT for AOD

RATIONALE: It is well established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D2 dopamine antagonist, has been shown to reduce alcohol craving and consumption. OBJECTIVE: To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, and randomized clinical trial was conducted. METHODS: One hundred twenty-nine treatment-seeking alcohol-dependent adults were randomly assigned to 12 weeks of olanzapine (5 vs. 2.5 mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days (PDD) to total days in treatment, alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. RESULTS: All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5 mg group experienced reduced craving for alcohol and participants in the 2.5 mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6 months post-treatment for the 2.5 mg group. Subjective experiences of the medication suggest that 2.5 and 5 mg were equally well tolerated. CONCLUSIONS: Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence.

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. TRIAL REGISTRATION: NCT02061293.

Aims: ED-based SBIRT for alcohol and drug use has the potential to impact public health greatly. Time and resource constraints limit implementation. Targeted intervention may be more efficient and practical. We hypothesized that we could use chief complaints to identify patients at highest risk of positive drug or alcohol use assessments. Methods: Using baseline data from NIDA CTN0047: SMARTED, free text chief complaints of 14,972 subjects from six sites were coded using a tested algorithm (Thompson, 2006). Multiple team members manually reviewed and further collapsed the chief complaint categorization to ensure agreement. We excluded subjects having missing data or complaints related to substance use and chief complaints stated by <15 subjects. Positive screens were defined as AUDIT-C > 4 for men and >3 for women (alcohol) and DAST > 2 (drugs). We ranked-ordered the chief complaints by their sensitivity and positive predictive value to (1) minimize the number of chief complaints and (2) assess the fewest number of ED patients. Our goal was to identify 75% of ED patients having positive assessments using these strategies. Results: The screening assessments were positive in 5805/14,561 (39.9%) for alcohol and 2454/14,494 (16.9%) for drugs. We collapsed the free-text chief complaints into 50 usable categories. To identify 75% of all ED patients having positive assessments using the first strategy would require including 19 chief complaints for alcohol screening and 20 chief complaints for drug screening. Adapting the second strategy, we would need to screen at least 71% and 68% of all ED patients for alcohol and drugs respectively to identify 75% of those having positive assessments. Conclusions: Based on this large, multicenter study, chief complaints provide little assistance in targeting SBIRT for alcohol or drug use in the ED

Individuals with alcohol use disorders (AUDs) have deficits in cognitive control, but how they change with treatment is unclear. Seven patients with AUD and anxiety from an open-label trial of disulfiram plus lorazepam performed a multisensory Stroop task during fMRI (both pre and post initiation of treatment), and were compared to nine healthy controls (HCs) (n = 16; Albuquerque, NM; years 2009-2012). Evoked BOLD signal and resting state functional connectivity were compared (HC vs. AUD; Scan 1 vs. Scan 2). AUD demonstrated hyperactivity and altered connectivity in the cognitive control network compared to HC, but treatment did not normalize function.