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Clinical trials for substance use disorder (SUD) often assess outcomes by aggregating substance use data into weekly proportions. However, daily substance use patterns may reveal how motivation changes during treatment. Neurocognitive principles of recency and expectancy indicate the salience of treatment mechanisms would increase on days proximal to therapy sessions. This study tested whether substance use decreased on days near treatment sessions.Bayesian multilevel models were used in a secondary analysis of randomized clinical trial data comparing cognitive behavioral therapy (CBT), computerized CBT, and treatment as usual during outpatient SUD treatment (The models suggested that substance use increased as more days passed after a therapy session (Substance use patterns during treatment were consistent with recency and expectancy neurocognitive principles. Substance use decreased on days closer to a therapy session, suggesting that treatment mechanisms were more salient on those days. More frequent therapeutic contact and targeted timing of treatment delivery may enhance treatment efficacy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ImportanceNovel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines.ObservationsConsensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications.Conclusions and RelevanceApplying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

There are few available culturally and linguistically adapted behavioral health interventions for substance use among Spanish-speaking adults. The authors describe the cultural adaptation of an innovative computer-based training for cognitive behavioral therapy program (CBT4CBT). Based in cognitive-behavioral skills training, CBT4CBT utilizes a

The allostatic model of addiction suggests that negative affect, such as depressive symptoms, mediates the effect of stress on outcomes among individuals with substance use disorders. However, few longitudinal treatment studies have demonstrated this effect. We analyzed data from a 12-week randomized trial of galantamine and/or computerized cognitive-behavioral therapy (CBT4CBT) for individuals (N = 120) with cocaine use disorder in methadone treatment for opioid use disorder. We evaluated baseline perceived stress as a predictor of end-of-treatment (EOT) substance use outcomes, and EOT perceived stress as a predictor of month 6 posttreatment outcomes. We conducted mediation models with intervening depressive symptoms as a mediator. We also explored whether CBT4CBT moderated the effects of perceived stress. Baseline perceived stress did not predict EOT outcomes (i.e., total effect). However, in mediation models, we found indirect effects of baseline perceived stress on EOT cocaine and illicit opioid use, via midtreatment depressive symptoms. EOT perceived stress had significant total effects on month 6 cocaine and illicit opioid use, and an indirect effect on month 6 illicit opioid use (but not cocaine use), via month 3 depressive symptoms. Alternative models with depressive symptoms as the predictor and perceived stress as a mediator revealed no indirect effects. The addition of CBT4CBT to standard methadone treatment did not moderate total or indirect effects of perceived stress on substance use. Depressive symptoms may play a mediating role in the prospective indirect effect of perceived stress on substance use outcomes, particularly illicit opioid use. Further research is needed on therapies targeting stress. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

This study sought to replicate and extend findings regarding change in the number of endorsed Diagnostic and Statistical Manual (DSM) criteria for substance use disorders as a meaningful outcome for clinical trials with Spanish-speakers. A secondary analysis was conducted of data from 83 treatment-seeking individuals with current DSM-IV substance dependence participating in a randomized controlled trial evaluating a culturally-adapted version of a computer-based cognitive behavioral therapy program (CBT4CBT) for Spanish-speakers. Participants were randomized to either weekly standard outpatient counseling (treatment as usual – TAU), or TAU plus access to CBT4CBT (TAU+CBT4CBT). The Structured Clinical Interview for DSM-IV (SCID-IV) was administered at baseline and at the end of the 8-week treatment period to measure change in diagnostic status and total criteria count. Frequency of substance use during treatment and throughout a 6-month follow-up period was measured by self-report using a calendar-based Timeline FollowBack method, with abstinence verified through instant urine toxicology, and problem severity was measured with the Addiction Severity Index (ASI). Results of a generalized linear model with Poisson’s distribution indicated significant reduction in the total count of DSM-IV dependence criteria during treatment (Wald X(2) = 136.20; p

Objective This meta-analysis examined 30 randomized controlled trials (32 study sites; 35 study arms) that tested the efficacy of cognitive-behavioral therapy (CBT) for alcohol or other drug use disorders. The study aim was to provide estimates of efficacy against three levels of experimental contrast (i.e., minimal [k = 5]; nonspecific therapy [k = 11]; specific therapy [k = 19]) for consumption frequency and quantity outcomes at early (1 to 6 months [kes = 41]) and late (8+ months [kes = 26]) follow-up time points. When pooled effect sizes were statistically heterogeneous, study-level moderators were examined. Method The inverse-variance weighted effect size was calculated for each study and pooled under random effects assumptions. Sensitivity analyses included tests of heterogeneity, study influence, and publication bias. Results CBT in contrast to minimal treatment showed a moderate and significant effect size that was consistent across outcome type and follow-up. When CBT was contrasted with a nonspecific therapy or treatment as usual, treatment effect was statistically significant for consumption frequency and quantity at early, but not late, follow-up. CBT effects in contrast to a specific therapy were consistently nonsignificant across outcomes and follow-up time points. Of 10 pooled effect sizes examined, two showed moderate heterogeneity, but multivariate analyses revealed few systematic predictors of between-study variance. Conclusions The current meta-analysis shows that CBT is more effective than a no treatment, minimal treatment, or nonspecific control. Consistent with findings on other evidence-based therapies, CBT did not show superior efficacy in contrast to another specific modality. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aims This meta-analysis reviewed 15 clinical trials (18 study sites/arms), examining the efficacy of an integrated cognitive-behavioral intervention (CBI) delivered to individuals with an alcohol or other drug use disorder and a co-occurring mental health disorder (AOD/MHD). Outcomes were alcohol or other drug use and mental health symptoms at post-treatment through follow-up. Methods The inverse-variance weighted effect size was calculated for each study and pooled under random effects assumptions. Results Integrated CBI showed a small effect size for AOD (g = 0.188, P = 0.061; I2 = 86%, τ2 = 0.126, k = 18) and MHD (g = 0.169, P = 0.024; I2 = 58%, τ2 = 0.052, k = 18) outcomes, although only MHD outcomes were statistically significant. Analysis by subgroup suggested that effect magnitude varied by type of contrast condition (integrated CBI + usual care vs. usual care only; integrated CBI vs. a single-disorder intervention), follow-up time point (post-treatment vs. 3–6 months) and primary AOD/MHD diagnosis, although these sub-groups often contained significant residual heterogeneity. In a series of mixed effects, meta-regression models, demographic factors were non-significant predictors of between-study heterogeneity. For AOD outcomes, greater effects were observed in higher quality studies, but study quality was not related to effect size variability for MHD outcomes. Conclusions The current meta-analysis shows a small and variable effect for integrated CBI with the most promising effect sizes observed for integrated CBI compared with a single disorder intervention (typically an AOD-only intervention) for follow-up outcomes, and for interventions targeting alcohol use and/or post-traumatic stress disorder. Given the clinical and methodological variability within the sample, results should be considered a preliminary, but important step forward in our understanding of treatment for co-occurring AOD/MHD.

OBJECTIVE: Abstinence outcomes are typically prioritized in the treatment of cocaine use disorder while ignoring patterns of low-frequency cocaine use. This study examined patterns of cocaine use frequency during treatment and evaluated how these patterns related to baseline characteristics and functioning outcomes 6 and 12 months after treatment. METHOD: We used a pooled dataset (N = 720) from seven randomized clinical trials for cocaine use disorder. The Addiction Severity Index (ASI) was used to assess functioning. Repeated-measures latent class analysis was used to derive patterns of cocaine use. RESULTS: Three patterns were identified: abstinence (10.6%), low-frequency use (approximately 1 day/week; 66.3%), and persistent frequent use (approximately 4 days/week; 23.1%). The low-frequency group was associated with male gender, younger age, and a criminal justice referral. The abstinent group had the highest alcohol problem severity score at baseline. At Month 6, the low-frequency group reported lower problem severity than the persistent frequent use group across multiple ASI areas, including the cocaine use as well as psychological, family, employment, and legal domains. At Month 12, the low-frequency group did not differ from the abstinent group in problem severity on any ASI domain and, relative to the persistent frequent use group, had lower cocaine use and employment problem severity. CONCLUSIONS: These findings highlight the importance of adopting a harm reduction approach and recognizing the potential clinical benefits associated with nonabstinent outcomes.

Cognitive-behavioral therapy (CBT) is one of the most evaluated behavioral interventions for substance use disorders, with considerable empirical evidence supporting its efficacy. However, despite CBT’s strong support from efficacy trials, broad dissemination and implementation have been challenging. Furthermore, there remains limited understanding regarding CBT’s mechanisms of behavior change; the theory-driven assumption that individuals acquire new skills for coping with triggers for substance use has notoriously lacked statistical support. The emergence of computer-delivered interventions has the potential to address dissemination and implementation challenges, as well as offer advantages toward understanding treatment mechanisms. This article will provide a summary of the current evidence supporting one particular computerized CBT program, CBT4CBT. Multiple clinical trials in different treatment settings have indicated CBT4CBT’s efficacy at reducing rates of alcohol and drug use when provided as an add-on to standard addiction treatment, as well as when provided with minimal clinical monitoring (i.e., virtual stand-alone). These effects have also been relatively durable after treatment termination, consistent with findings of traditional CBT. It is important to note that the evaluation of individuals’ cognitive and behavioral coping skills prior and following treatment has indicated the acquisition/improvement of these skills may be a mechanism of behavior change for those who engage with CBT4CBT. Thus, computerized delivery may be a strategy for enhancing individuals’ learning of cognitive and behavioral skills for successfully avoiding substance use. Future work should aim to identify the optimal type of setting, clinician role, and patient characteristics for targeted dissemination and implementation.

Background Substantial efforts have been made to identify clinically meaningful non-abstinence cocaine use outcomes by establishing associations between targeted drug use outcomes and long-term functional improvements. Psychiatric symptomatology is prevalent among those seeking treatment for cocaine use disorder (CUD). Establishing an association between cocaine use outcomes and improvements in psychiatric symptomatology would support clinical validity to these outcome measures. Method With data pooled from 5 clinical trials evaluating treatment for CUD (n = 474) multiple linear mixed models were conducted to determine how five specific cocaine use outcome measures performed in terms of improvements in psychiatric symptomatology assessed with the Brief Symptom Inventory (BSI) at baseline, end-of-treatment and 6-month follow-up. Results Three outcome measures performed comparably well (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence), in that they consistently predicted improvements in several BSI composite scores at the end-of-treatment and follow-up. The poorer-performing outcome measures were complete abstinence during treatment, percentage of negative urinalysis results and percentage of days abstinent. Improvements in the BSI’s global index of distress, positive symptom total, as well as depression, interpersonal sensitivity, obsessive-compulsion, phobic-anxiety and psychoticism dimensions were consistently associated with outcome effects, while anxiety, hostility, paranoid ideation and somatization were not. Conclusion The consistent short and long-term association of three outcome measures evaluated here (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence) with improvements psychiatric symptomatology adds support to their clinical relevance as well as their adoption in trials and treatments for CUD.

Background Assessment instruments commonly used in clinical trials to measure functional outcomes in substance users may lack sensitivity to detect change during treatment, potentially limiting findings regarding benefits of reduced drug use. This study evaluated the sensitivity of the Addiction Severity Index (ASI) to detect change in psychiatric functioning among cocaine users. Methods Data were pooled across five clinical trials for cocaine use disorder (N = 492) that included a 12-week treatment period and 6-month follow-up. Within-person cohen’s d′ was used to evaluate effect size of change on the Psychiatric Composite Score of the ASI (ASI-Psych) and Global Severity Index (GSI) of the Brief Symptom Inventory, as well as cocaine use. Results Effect sizes were larger for GSI than ASI-Psych from baseline to week 12 (GSI d′ = 0.59; ASI-Psych d′ = 0.16), and 6-month follow-up (GSI d′ = 0.48; ASI-Psych d′ = 0.10). For those with non-zero ASI-Psych at baseline (n = 252), medium effect sizes were found over the 12-week period (d′ = 0.53) and 6-month follow-up (d′ = 0.47). Effect sizes for change in days of cocaine use were most similar to GSI in either sample. Conclusions The ASI Psychiatric Composite Score may have limited sensitivity to detect change in psychiatric functioning among clinical trial participants who reduce cocaine use. It may be useful for detecting change amongst those reporting some psychiatric problems at the start of treatment. Future research should consider an instrument’s sensitivity to change when assessing the potential functional benefits of reducing cocaine use.

BACKGROUND Computer-based delivery of cognitive behavioral therapy (CBT) may be a less costly approach to increase dissemination and implementation of evidence-based treatments for alcohol use disorder (AUD). However, comprehensive evaluations of costs, cost-effectiveness, and cost-benefit of computer-delivered interventions are rare. METHODS This study used data from a completed randomized clinical trial to evaluate the cost-effectiveness and cost-benefit of a computer-based version of CBT (CBT4CBT) for AUD. Sixty-three participants were randomized to receive one of the following treatments at an outpatient treatment facility and attended at least one session: (1) treatment as usual (TAU), (2) CBT4CBT plus treatment as usual (CBT4CBT+TAU), or (3) CBT4CBT plus brief monitoring. RESULTS Median protocol treatment costs per participant differed significantly between conditions, Kruskal-Wallis H(2) = 8.40, p = 0.02, such that CBT4CBT+TAU and CBT4CBT+monitoring each cost significantly more per participant than TAU. However, when nonprotocol treatment costs were included, total treatment costs per participant did not differ significantly between conditions. Median incremental cost-effective ratios (ICERs) revealed that CBT4CBT+TAU was more costly and more effective than TAU. It cost $35.08 to add CBT4CBT to TAU to produce a reduction of one additional drinking day per month between baseline and the end of the 8-week treatment protocol: CBT4CBT+monitoring cost $33.70 less to produce a reduction of one additional drinking day per month because CBT4CBT+monitoring was less costly than TAU and more effective at treatment termination, though not significantly so. Net benefit analyses suggested that costs of treatment, regardless of condition, did not offset monthly costs related to healthcare utilization, criminal justice involvement, and employment disruption between baseline and 6-month follow-up. Benefit-cost ratios were similar for each condition. CONCLUSIONS Results of this pilot economic evaluation suggest that an 8-week course of CBT4CBT may be a cost-effective addition and potential alternative to standard outpatient treatment for AUD. Additional research is needed to generate conclusions about the cost-benefit of providing CBT4CBT to treatment-seeking individuals participating in standard outpatient treatment.

Cognitive-behavioral therapy (CBT) is effective across a range of substance use disorders yet implementation in many substance use treatment settings is comparatively rare due to multiple challenges, including the costly resources needed for appropriate training and supervision of clinicians. Digital technology is one strategy to address these challenges, potentially making such evidence-based therapies more broadly available to those in need of treatment. This chapter provides an overview of the development of a computerized version of CBT (CBT4CBT) as a means of exposing patients to basic CBT skills and strategies in an engaging and user-friendly manner while also allowing clinicians and treatment programs to be more efficient and effective. Empirical evidence supporting CBT4CBT from four randomized trials at the time of writing is reviewed, as well as a description of the potential benefits and applications of computerized therapies. Given their flexibility, relative ease of dissemination, and lower cost compared to clinician-delivered treatment, computerized versions of CBT (and other behavioral therapies) might be used to enhance and extend psychiatric treatment for addictions. Moreover, the level of standardization and control that characterizes computerized therapies may be useful in understanding mechanisms of effective treatments and in development of personalized interventions. While there is tremendous optimism regarding the potential of computerized therapies, such as CBT4CBT, systematic evaluation of these interventions and the methodological standards for evaluating them is still in very early stages relative to the more established behavioral and pharmacologic interventions for addictions.

Background No studies have examined long-term changes in substance-related coping skills as a statistical mediator of cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Methods We tested both short- and long-term changes in coping as mediators of treatment effects in two trials of in-person and/or computerized CBT for SUD. The first trial included 137 individuals (75 % male; 65.7 % non-White; mean age = 35.9) with drug and/or alcohol use disorders randomized to one of the following: in-person CBT, computer-delivered CBT (CBT4CBT) plus brief monitoring, or treatment-as-usual (TAU). The second trial included 68 individuals (65 % male; 66.2 % non-white; mean age = 42.7) with an alcohol use disorder randomized to one of the following: CBT4CBT plus brief monitoring, CBT4CBT plus TAU, or TAU only. Coping was assessed with the Coping Strategies Scale. Latent growth curve mediational models were conducted, with both short-term (baseline through end-of-treatment) and long-term (baseline through 3-month post-treatment follow-up) changes in coping. Results There were no mediation effects for short-term changes in coping. However, in both trials, there were significant mediation effects for long-term changes in coping: In trial 1, the effect of CBT4CBT vs. TAU on substance use at the 6-month follow-up was mediated by long-term increases in coping. This same mediation effect was not found for in-person CBT vs. TAU. In trial 2, the effect of CBT4CBT vs. not receiving CBT4CBT on heavy drinking at the 6-month follow-up was mediated by long-term increases in coping. Conclusions Long-term increases in coping may be a mechanism of change in computerized CBT for SUD.

This study tests for measurement invariance of impulsivity assessed by the Barratt Impulsiveness Scale (BIS) across Black and White adults with cocaine use disorder and examines the association of BIS impulsivity with treatment retention and outcomes. Data from four clinical trials were combined providing a total sample of 302 participants with cocaine abuse/dependence (42% Black, 58% White, 44% female, age(mean) = 40.22, SD = 9.26). We used multi-group confirmatory factor analyses to test for measurement invariance across race and examined bivariate correlations between BIS impulsivity and treatment retention and outcomes by race. Factor analyses indicated a 22-item, two-factor (motor impulsiveness and nonplanning impulsiveness) brief BIS fit the data best (RMSEA=.073 [90% CI: .065–.080]; CFI=.904; TLI=.893; SRMR=.073) and was configural, metric, and scalar invariant across race. Higher motor impulsiveness was associated with higher percentage cocaine negative urines in the overall sample (r = −.15, p=.01), but this association only remained in the Black subsample when examined across race (r = .28, p

Background The theoretical benefits of naltrexone as a treatment for opioid use disorder (e.g., safety, non-addictive, low risk of diversion) stand in sharp contrast to its disappointing record on retention in most samples. The relationship of uncomfortable physical and dysphoric symptoms to retention on naltrexone is a controversial and under-studied issue. Methods Using data from a randomized controlled trial of voucher-based contingency management and support from a significant other to enhance retention on oral naltrexone, we compared self-reported somatic and dysphoric symptoms, measured weekly, for individuals who were retained on naltrexone through the 12-week trial (n = 50) versus those who dropped out (n = 70). Results There were no differences between participants who completed treatment and those who dropped out on multiple baseline characteristics, including somatic or affective symptoms prior to treatment. However, whether analyzed cross-sectionally or over time, participants who dropped out consistently reported higher rates of somatic symptoms, particularly difficulty sleeping, as well as affective symptoms, including multiple indicators of depression, anxiety, and anhedonia. Conclusions Although the smaller group of participants who were retained on oral naltrexone for 12 weeks reported decreasing physical and affective discomfort over time, there was substantial evidence that those who dropped out experienced continued and significant levels of distress. Individuals who report physical or affective distress while taking naltrexone may be at higher risk of dropout.

Objectives. To evaluate whether adding Web-based cognitive behavioral treatment (CBT) to standard outpatient psychiatric or addiction treatment improved substance use outcomes. Methods. We conducted a randomized clinical trial in New Haven, Connecticut, between 2014 and 2017 comparing 8 weeks of standard outpatient treatment to the same treatment with access to a culturally adapted version of Web-based CBT with a 6-month follow-up. Participants were 92 treatment-seeking individuals with Spanish as their primary language and current substance use disorder, with few other restrictions. Results. Treatment completion and data availability were high (98% of the randomized sample). For the primary outcome (change in frequency of primary substance used), there was a significant effect of treatment condition by time (t 1, 718 = −2.64; 95% confidence interval = −0.61, 0.09; P = .01), indicating significantly greater reductions for those assigned to Web CBT, which were durable through the 6-month follow-up. The knowledge test indicated significantly greater increases for those assigned to Web CBT. Conclusions. Adding a culturally adapted version of Web-based CBT to standard treatment improved substance use outcomes. Public Health Implications. This approach has high potential to address health disparities by providing an easily accessible, inexpensive form of evidence-based treatment to a range of Latinos with substance use disorders.

Previous trials have demonstrated the efficacy and durability of computer-based cognitive-behavioral therapy (CBT4CBT) as an add-on to standard outpatient care in a range of treatment-seeking populations. In this study, the authors evaluated the efficacy and safety of CBT4CBT as a virtual stand-alone treatment, delivered with minimal clinical monitoring, and clinician-delivered cognitive-behavioral therapy (CBT) compared with treatment as usual in a heterogeneous sample of treatment-seeking outpatients with substance use disorders.This was a randomized clinical trial in which 137 individuals who met DSM-IV-TR criteria for current substance abuse or dependence were randomly assigned to receive treatment as usual, weekly individual CBT, or CBT4CBT with brief weekly monitoring.Rates of treatment exposure differed by group, with the best retention in the CBT4CBT group and the poorest in the individual CBT group. Participants who received CBT or CBT4CBT reduced their frequency of substance use significantly more than those who received treatment as usual. Six-month follow-up outcomes indicated continuing benefit of CBT4CBT (plus monitoring) over treatment as usual, but not for clinician-delivered CBT over treatment as usual. Analysis of secondary outcomes indicated that participants in the CBT4CBT group demonstrated the best learning of cognitive and behavioral concepts, as well as the highest satisfaction with treatment.This first trial of computerized CBT as a virtual stand-alone intervention delivered in a clinical setting to a diverse sample of patients with current substance use disorders indicated that it was safe, effective, and durable relative to standard treatment approaches and was well-liked by participants. Clinician-delivered individual CBT, while efficacious within the treatment period, was unexpectedly associated with a higher dropout rate and lower effects at follow-up.

The emphasis in addictions research has shifted toward a greater interest in identifying the mechanisms involved in patient behavior change. This systematic review investigated nearly 30 years of mediation research on cognitive behavioral therapy (CBT) for alcohol or other drug use disorders (AUD/SUD). Method Study inclusion criteria targeted analyses occurring in the context of a randomized clinical trial where both intervention/intervention ingredient to mediator (a path) and mediator to outcome (b path) paths were reported. Between- and within-condition analyses were eligible, as were studies that formally tested mediation and those that conducted path analysis only. Results The review sample included K = 15 reports of primarily between-condition analyses. Almost half of these reports utilized Project MATCH (k = 2) or COMBINE (k = 4) samples. Among the mediator candidates, support for changes in coping skills was strongest, although the specificity of this process to CBT or CBT-based treatment remains unclear. Similarly, support for self-efficacy as a statistical mediator was found in within-, but not between-condition analyses. Conclusions A coherent body of literature on CBT mechanisms is significantly lacking. Adopting methodological guidelines from the Science of Behavior Change Framework, we provide recommendations for future research in this area of study.

There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria.

Background Sustained abstinence is currently the only accepted end-point for pharmacotherapy trials for most substance use disorders (SUD), with the exception of alcohol. Despite recent efforts, the identification of a non-abstinence alternative as a clinically meaningful end-point for drug use trials has been elusive. Argument and analysis The current standard for establishing a clinically meaningful outcome in SUD trials is to demonstrate that a reduction in drug use is associated with improvement in long-term functioning, but data indicate relatively weak associations between drug use and various psychosocial problem domains. This may be because assessments used most commonly to measure an individual's functioning do not specify whether aspects of functioning are a direct consequence of drug use. The acceptance of a non-abstinence-based end-point for alcohol use disorder trials was supported in part through associations with reductions in alcohol-related consequences, although measures designed to assess the direct consequences of drug use are rarely included in drug treatment efficacy trials. Conclusions The field of substance use disorders should include measures of negative psychosocial and health consequences of drug use, as opposed to overall functioning, in the effort to establish meaningful non-abstinence-based end-points.

BACKGROUND Most clinical trials evaluating treatments for alcohol use target individuals meeting diagnostic criteria for alcohol use disorder (AUD), but few address change in diagnostic status following treatment or as a potential outcome indicator. This study evaluated whether DSM-5 AUD total criteria count or severity category was sensitive to change over time and treatment effects. METHODS Data were drawn from a randomized clinical trial that evaluated the efficacy of computer-based cognitive behavioral therapy program (CBT4CBT) for AUD. Sixty-eight individuals were randomized to 1 of the 3 weekly outpatient treatments for an 8-week period: (i) treatment as usual (TAU), (ii) TAU+CBT4CBT, and (iii) CBT4CBT+brief monitoring. Structured clinical interviews were used to determine current (past 30 days) AUD diagnosis at baseline, end-of-treatment, and 6 months following end-of-treatment. Change in the total number of DSM criteria endorsed, as well as severity categories (mild, moderate, severe), was evaluated across time and by treatment condition. RESULTS Generalized Poisson's linear mixed models revealed a significant reduction in the number of DSM criteria from baseline to treatment end point [time effect χ2 (1) = 35.54, p

Background Poor performance on Drug Stroop tasks, which could indicate attentional bias to drug-related cues, craving, poor cognitive control (including poor response inhibition), has been associated with substance use severity, treatment retention and substance use treatment outcomes. Cognitive Behavioral Therapy (CBT) focuses on training in appraisal and coping strategies, including strategies to minimize the negative impact of triggers and coping with drug-cue-induced craving. One mechanism of action of CBT may be the strengthening of cognitive control processes and reduction of attentional bias to drug-related stimuli. Methods Methadone-maintained individuals with cocaine-use disorders, participating in a randomized controlled trial of treatment as usual (TAU) versus TAU plus access to computer-based CBT (CBT4CBT), completed a computerized Drug Stroop task at pre- and post-treatment. Analyses determined whether attentional bias toward drug-related stimuli changed differentially by treatment group or cocaine use outcomes across the treatment period and whether engagement in components of CBT4CBT or TAU treatment related to changes in attentional bias toward drug-related stimuli at post- versus pre-treatment. Results Participants achieving a longer duration of cocaine abstinence during treatment (3+ weeks) showed greater reductions in Drug Stroop Effect than those with shorter maximum continuous abstinence. Reductions in Drug Stroop Effect across treatment were associated with greater engagement with CBT4CBT-specific treatment components, but not TAU-specific treatment components. Conclusions Reduction in attentional bias to drug-related cues and craving and/or improved executive cognitive control and response inhibition may contribute to the mechanism of action of CBT4CBT.

Establishing a non-abstinence cocaine use outcome as clinically meaningful has been elusive, in part due to the lack of association between cocaine use outcomes and meaningful indicators of long-term functioning.Using data pooled across 7 clinical trials evaluating treatments for cocaine (N=718), a dichotomous indicator of functioning was created to represent a meaningful outcome ('problem-free functioning' - PFF), defined as the absence of problems across non-substance-related domains on the Addiction Severity Index. Its validity was evaluated at multiple time points (baseline, end-of-treatment, terminal follow-up) and used to explore associations with cocaine use.The percentage of participants meeting PFF criteria increased over time (baseline=18%; end-of-treatment=32%; terminal follow-up=37%). At each time point, ANOVAs indicated those who met PFF criteria reported significantly less distress on the Brief Symptom Inventory and less perceived stress on the Perceived Stress Scale. Generalized linear models indicated categorical indices of self-reported cocaine use at the end of treatment were predictive of the probability of meeting PFF criteria during follow-up (β=-0.01, p0.01; 95% CI: -0.008 to -0.003), with those reporting 0days or 1-4days ('occasional' use) in the final month of treatment showing an increased likelihood of achieving PFF.Initial validation of a proxy indicator of problem-free functioning demonstrated criterion validity and sensitivity to change over time. Frequency of cocaine use in the final month of treatment was associated with PFF during follow-up, with strongest associations between PFF and abstinence or 'occasional' use.

BackgroundCognitive-behavioral therapy (CBT) has long-standing evidence for efficacy in the treatment of alcohol use, yet implementation in clinical practice has been challenging. Delivery of CBT through technology-based platforms, such as web-based programs and mobile applications, has the potential to provide widespread access to this evidence-based intervention. While there have been reviews indicating the efficacy of technology-based delivery of CBT for various psychiatric conditions, none have focused on efficacy for alcohol use. The current meta-analysis was conducted to fill this research gap.MethodsDescriptive data were used to characterize the nature of the literature on technology-delivered, CBT-based interventions for alcohol use ("CBT Tech"). Inverse-variance-weighted effect sizes were calculated, and random effects, effect sizes were pooled in 4 subgroups.ResultsFifteen published trials conducted primarily with at-risk or heavy drinkers were identified. Of these studies, 60% explicitly targeted alcohol use moderation. The content of CBT Tech programs varied, ranging from 4 to 62 sessions/exercises, with many programs combining elements of motivational interviewing (47%). With respect to efficacy, CBT Tech as a stand-alone treatment in contrast to a minimal treatment control showed a positive and statistically significant, albeit small effect (g=0.20: 95% CI=0.22, 0.38, kes =5). When CBT Tech was compared to treatment as usual (TAU), effects were nonsignificant. However, when CBT Tech was tested as an addition to TAU, in contrast to TAU only, the effect size was positive, significant (g=0.30: 95% CI=0.10, 0.50, kes =7), and stable over 12-month follow-up. Only 2 studies compared CBT Tech to in-person CBT, and this pooled effect size did not suggest superior efficacy.ConclusionsThese results show a benefit for technology-delivered, CBT-based interventions as a stand-alone therapy for heavy drinking or as an addition to usual care in specialty substance use settings.

There is a critical need for research on clinical features that may influence response to treatment for opioid use disorder (OUD). Given its neurobiology and relevance to opioid use, anhedonia may be one such promising clinical feature. We identified and reviewed 11 studies that measured anhedonia in humans with OUD to characterize the current state of evidence and highlight potential implications for treatment. The majority of studies were cross-sectional, indicating higher anhedonia scores in opioid-dependent samples compared with healthy control subjects. Rates of participants with clinically significant anhedonia ranged from 21% to 48%. Anhedonia scores were correlated with opioid craving and use; however, there are significant knowledge gaps regarding its time course and impact on treatment adherence and outcomes. Repeated assessment of anhedonia early in treatment for OUD is recommended because it may be a unique predictor of dropout or nonresponse and a potential target for behavioral and/or pharmacological intervention.

Background Unemployment is a chronic problem among treatment seeking substance users and is associated with poor treatment response. Most studies that have examined the relationship between employment and treatment outcomes for substance use disorders have done so by considering employment at only one specific point in time (e.g., upon entering treatment). There is a lack of research on how change in employment status over time is associated with substance use treatment outcomes. The aim of this study was to evaluate both static employment status and change in employment status over time as predictors of cocaine use treatment outcomes. Methods We utilized data pooled from six randomized clinical trials evaluating treatment for cocaine use disorders (n = 553). Multiple general linear mixed models were conducted to determine the association of baseline, end-of-treatment, and change in employment status (from baseline to end-of-treatment) with treatment outcomes. Results Treatment outcomes did not differ by baseline employment status but were significantly better for those employed versus unemployed at the end-of-treatment. In regard to change in employment status over time, those who were unemployed at baseline and acquired employment by end-of-treatment had significantly better treatment outcomes during active treatment and follow-up, as compared to those who were unemployed at baseline and remained unemployed by end-of-treatment. Conclusion Our findings suggest that end-of-treatment employment status may be an important marker of good outcome among those unemployed at treatment entry and support the incorporation of interventions designed to promote employment by substance use disorders treatment programs.

Cognitive behavioral therapy (CBT) is one of the most common and effective treatments for substance use disorders (SUD); however, effective delivery of CBT depends on a wide variety of nuanced skills that require practice to master. We created a computer-based simulation training system to support the development of necessary skills for student trainees to be able to apply CBT effectively for clients with SUDs. CBT: Introducing Cognitive Behavioral Therapy is an interactive, role-play simulation that provides opportunities for clinician trainees to hone their skills through repeated practice and real-time feedback before application in a clinical setting. This is the first study that tests whether such a simulation improves trainee skills for the treatment of clients with SUDs. Graduate students (N = 65; social work, clinical psychology) completed standardized patient (SP) interviews, were randomized to the simulation training program or manual comparison condition (Project MATCH manual), and completed SP interviews three months post-baseline. Using general linear models, results indicated a significant time x group effect, with students assigned to the simulation training program showing greater improvement in “extensiveness” and “skillfulness” ratings across three skill categories: general agenda setting (p = .03), explaining CBT concepts (p = .007), and understanding of CBT concepts (p = .001). However, manual comparison participants showed greater improvement than simulation trainees in “assessing primary drug use” (prange = .013–.024). No changes in extensiveness or skillfulness of motivational interviewing (MI) style were observed. This pilot test of CBT: Introducing Cognitive Behavioral Therapy offers support for use of this novel technology as a potential approach to scale up CBT training for students, and perhaps clinicians, counseling people with SUDs.

Background Most published treatment trials for cocaine use disorders (CUD) have been conducted with samples composed predominantly of White men and underrepresent women and racial/ethnic minorities. Because of the high prevalence of men and White individuals in CUD treatment trials, results from studies that have compared treatment outcomes by gender and race or ethnicity separately may not be representative of women or racial/ethnic minorities. Methods With a sample pooled from seven randomized clinical trials of treatment for CUD (n = 629), baseline characteristics and treatment outcome responses were compared with 4 subgroups of individuals created based on the intersection of gender and race (White men, Black men, White women and Black women). Results At baseline, sociodemographic status, pattern, frequency and severity of cocaine use, psychiatric comorbidities, employment and legal problems significantly differed across groups. Treatment outcome indicators collected during treatment and through follow-up, consistently indicated poorer outcomes among the sample of White women, but were similar for the other groups. Conclusions Men and women with CUD from both racial groups enter treatment with different psychosocial issues (e.g., history of violence/trauma, financial problems, co-occurring psychiatric disorders) and substance use problems (e.g. types of substances) that may impact treatment outcomes and indicate a need for culturally-informed care to deliver more effective treatment for CUD. Poorer overall outcomes among White women may reflect the need for a more focused treatment approach for this group; and highlight the importance of evaluating gender and race in treatment trials to better address health disparities.

Background Cognitive behavioral therapy (CBT) is an evidence-based treatment for alcohol use disorders (AUDs), yet is rarely implemented with high fidelity in clinical practice. Computer-based delivery of CBT offers the potential to address dissemination challenges, but to date there have been no evaluations of a web-based CBT program for alcohol use within a clinical sample. Methods This study randomized treatment-seeking individuals with a current AUD to 1 of 3 treatments at a community outpatient facility: (i) standard treatment as usual (TAU); (ii) TAU plus on-site access to a computerized CBT targeting alcohol use (TAU + CBT4CBT); or (iii) CBT4CBT plus brief weekly clinical monitoring (CBT4CBT + monitoring). Participant alcohol use was assessed weekly during an 8-week treatment period, as well as 1, 3, and 6 months after treatment. Results Sixty-eight individuals (65% male; 54% African American) were randomized (TAU = 22; TAU + CBT4CBT = 22; CBT4CBT + monitoring = 24). There were significantly higher rates of treatment completion among participants assigned to 1 of the CBT4CBT conditions compared to TAU (Wald = 6.86, p

Importance Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD. Objective To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs. Data Sources PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019. Study Selection Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included. Data Extraction and Synthesis Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects. Main Outcomes and Measures Substance use frequency and quantity outcomes after treatment and during follow-up were examined. Results The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (grange, 0.18-0.28;k = 9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target. Conclusions and Relevance The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.

There are multiple challenges toward the identification and acceptance of a meaningful reduction-based endpoint for use in drug use disorder medication efficacy clinical trials. Evaluation of change in diagnostic criteria, and severity metrics based on criterion counts, may be a promising approach for future research.

Background Despite calls for non-abstinence endpoints in randomized clinical trials (RCTs) for cocaine use disorder, there is a lack of data validating non-abstinence endpoints. We conducted a clinical validation of reduction in cocaine frequency level as a non-abstinence endpoint in RCTs for cocaine use disorder (CUD). Methods We utilized a pooled dataset (n = 716; 63.6 % male, 51.4 % non-Hispanic white) from seven RCTs for CUD. We specified three cocaine frequency levels at baseline and end of treatment (EOT): abstinence, low frequency (1–4 days/month), and high frequency (5+ days/month). Multiple regression analyses were conducted. Results Among the sample, 38.3 % had at least a one-level reduction from baseline to EOT, whereas 61.7 % did not change/increased frequency level. At least a one-level reduction in cocaine frequency level from baseline to EOT versus no change/increase was significantly associated with better functioning up to one year following treatment on measures of cocaine use, as well as psychological, employment, legal, and other drug use problem severity domains of the Addiction Severity Index (ASI). We also conducted analyses only among those at the high frequency level at baseline and found those who reduced to low frequency use at EOT had similar outcomes at follow-up as those who reduced to abstinence. Conclusions At least a one-level reduction in cocaine frequency level from pretreatment to EOT can be a clinically meaningful endpoint given its relation to sustained clinical benefit up to one-year following treatment. These data parallel recent findings regarding reduction in drinking risk level among individuals with alcohol use disorder.

Background and Objectives The relationship between patients’ baseline expectations regarding treatment outcome and actual outcomes has not been widely studied within the field of substance use disorders. We hypothesized that outcome expectations would be unrelated to outcomes in a study investigating motivational enhancement therapy delivered in English (MET-E) consistent with our earlier work, and conducted exploratory analyses in a separate study that investigated the same treatment delivered in Spanish (MET-S). Methods These secondary analyses compared patient outcome expectations and substance use treatment outcomes in two large, multisite randomized controlled clinical trials that evaluated three sessions of MET-E or MET-S. The MET-E sample included 461 participants and the MET-S sample included 405 participants. Outcome expectations were measured by a single item regarding expectations about abstinence prior to initiating treatment. Results Outcome expectations were strongly associated with most substance use outcomes in the MET-S trial (but not in MET-E), even after controlling for severity of substance use at baseline. In MET-S, those who indicated that they were “unsure” that they would achieve abstinence during treatment submitted a greater percentage of drug-positive urine toxicology screens during the treatment period than those who were ‘sure’ they would achieve abstinence (F = 18.83, p

Background The current review revisits the article entitled: “Active Ingredients: How and Why Evidence-Based Alcohol Behavioral Treatment Interventions Work” published in Alcoholism: Clinical and Experimental Research. This work summarized proceedings from a 2004 Symposium of the same name that was held at the Annual Meeting of the Research Society on Alcoholism (RSA). A decade has passed, which provides occasion for an evaluation of progress. In 2014, an RSA symposium titled Active Treatment Ingredients and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later did just that. Methods The current review revisits state-of-the-art research on the 3 treatments examined 10 years ago: cognitive behavioral therapy, alcohol behavior couples therapy, and 12-step facilitation. Because of its empirically validated effectiveness and robust research agenda on the study of process outcome, motivational interviewing has been selected as the fourth treatment modality to be discussed. For each of these 4 treatments, the reviewers provide a critical assessment of current theory and research with a special emphasis on key recommendations for the future. Results Noteworthy progress has been made in identifying active ingredients of treatments and mechanisms of behavior change in these 4 behavioral interventions for alcohol and other drug use disorders. Not only have we established some of the mechanisms through which these evidence-based treatments work, but we have also uncovered some of the limitations in our existing frameworks and methods. Conclusions Further progress in this area will require a broader view with respect to conceptual frameworks, analytic methods, and measurement instrumentation.

Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, im- provements in cognitive performance are often observed in the control groups of RCTs as well. There has been no comprehensive examination of change in control groups for CR, which may inform trial methodology and improve our understanding of measured out- comes for cognitive remediation. In this meta-analysis, we calculated pre-post change in cognitive test performance within control groups of RCTs in 32 CR trials (n = 794 par- ticipants) published between 1970 and 2011, and examined the association between pre- post change and sample size, duration of treatment, type of control group, and participants' age, intelligence, duration of illness, and psychiatric symptoms. Results showed that control groups in CR trials showed small effect size changes (Cohen's d = 0.12 ± 0.16) in cognitive test performance over the trial duration. Study characteristics associated with pre-post change included participant age and sample size. These findings suggest attention to change in control groups may help improve detection of cognitive remediation effects for schizophrenia.

A substantial portion of individuals entering treatment for substance use have been referred by the criminal justice system, yet there are conflicting reports regarding treatment engagement and outcome differences compared to those not referred. This study examined baseline characteristic and treatment outcome differences among cocaine-dependent individuals participating in cocaine treatment randomized trials.This secondary analysis pooled samples across five completed randomized controlled trials, resulting in 434 participants. Of these, 67 (15%) were prompted to treatment by the criminal justice system.This subsample of criminal justice prompted (CJP) individuals did not differ from those not prompted by the criminal justice system in terms of gender, race/ethnicity, marital status, or age. However, the CJP group reported more years of regular cocaine use, more severe employment and legal problems, as well as less readiness to change prior to treatment. Treatment outcomes did not differ significantly from those without a criminal justice prompt, and on some measures the outcomes for CJP group were better (e.g., percentage of days cocaine abstinent, number of therapy sessions attended).These findings suggest that being prompted to treatment by the criminal justice system may not lead to poorer treatment engagement or substance use outcomes for individuals participating in randomized controlled treatment trials.Despite some baseline indicators of poorer treatment prognosis, individuals who have been prompted to treatment by the criminal justice system have similar treatment outcomes as those presenting to treatment voluntarily.

The limited role of therapists in some technology-based interventions raises questions as to whether clients may develop a ‘working alliance’ with the program, and the impact on relationships with a therapist and/or treatment outcomes. In this study, the Working Alliance Inventory (WAI), and an adapted version for technology-based interventions (WAI-Tech), were administered within a subsample (n = 66) of cocaine-dependent individuals participating in a randomized trial evaluating the efficacy of Computer-Based Training for Cognitive Behavioral Therapy (CBT4CBT) as an adjunct to treatment as usual (TAU). Results suggest the WAI-Tech has relatively similar psychometric characteristics as the standard WAI; however the ‘bond’ subscale scores were lower on the WAI-Tech [F(1,52) = 5.78, p