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Reports from uncontrolled trials and surveys suggest that there are disparities in substance-use outcomes for minoritised racial and ethnic populations, yet few of these disparities have emerged from randomised clinical trials (RCTs). We conducted a systematic review of RCTs published in English of Black or Latinx adults with any non-nicotine substance use disorder that reported rates of treatment initiation, engagement, or substance-use outcome by race or ethnicity. Study quality was assessed by the Joanna Briggs Institute appraisal tool and a Yale internally validated quality assessment. Of the 5204 studies, 50 RCTs met the inclusion criteria, all done in the USA, 24 compared treatment initiation, engagement, or outcome across races or ethnicities and 26 compared these same factors within a race. Few RCTs have reported outcomes specifically for Black or Latinx populations, with nine reporting significant differences by race or ethnicity. Significant differences were found in all studies that evaluated the baseline differences in social determinants. This Review explains the need for optimisation of RCTs to inform the design, delivery, and dissemination of treatment to historically excluded communities.

There are no approved medications for the treatment of cocaine use disorder (CUD). Modafinil, a cognitive-enhancer with weak stimulant-like effects, has shown promise in initial studies as a treatment for CUD. Its potential efficacy has not been examined in individuals dually dependent on cocaine and opioids.This study examined the efficacy of modafinil, in combination with contingency management (CM), for reducing cocaine and opioid use and improving cognitive function in methadone-stabilized individuals with opioid and cocaine dependence. We conducted a 17-week, double-blind, randomized controlled trial in which participants were randomized to one of four conditions: 1) modafinil + CM; 2) modafinil + yoked-control (YC); 3) placebo +CM; or 4) placebo + YC. Additionally, all subjects received platform treatments of cognitive behavioral therapy (CBT) and methadone. While the original planned sample size was N=160, a total of 91 participants were randomized. The two primary cocaine use outcomes were percentage of urine specimens positive for cocaine and percent of days of self-reported abstinence from cocaine during treatment. Cognitive function, opioid use, and secondary cocaine use outcomes were also considered.Modafinil was well-tolerated with minimal reports of adverse effects. Modafinil was no more effective than placebo in reducing cocaine or opioid use or improving cognitive performance.In the context of a trial with robust control conditions and platform treatments, findings did not provide support for the efficacy of modafinil treatment for the treatment of CUD in methadone-stabilized individuals with dual opioid and cocaine dependence.

An important part of children's social and cognitive development is their understanding that people are psychological beings with internal, mental states including desire, intention, perception, and belief. A full understanding of people as psychological beings requires a representational theory of mind (ToM), which is an understanding that mental states can faithfully represent reality, or misrepresent reality. For the last 35 years, researchers have relied on false-belief tasks as the gold standard to test children's understanding that beliefs can misrepresent reality. In false-belief tasks, children are asked to reason about the behavior of agents who have false beliefs about situations. Although a large body of evidence indicates that most children pass false-belief tasks by the end of the preschool years, the evidence we present in this monograph suggests that most children do not understand false beliefs or, surprisingly, even true beliefs until middle childhood. We argue that young children pass false-belief tasks without understanding false beliefs by using perceptual access reasoning (PAR). With PAR, children understand that seeing leads to knowing in the moment, but not that knowing also arises from thinking or persists as memory and belief after the situation changes. By the same token, PAR leads children to fail true-belief tasks. PAR theory can account for performance on other traditional tests of representational ToM and related tasks, and can account for the factors that have been found to correlate with or affect both true- and false-belief performance. The theory provides a new laboratory measure which we label the belief understanding scale (BUS). This scale can distinguish between a child who is operating with PAR versus a child who is understanding beliefs. This scale provides a method needed to allow the study of the development of representational ToM. In this monograph, we report the outcome of the tests that we have conducted of predictions generated by PAR theory. The findings demonstrated signature PAR limitations in reasoning about the mind during the ages when children are hypothesized to be using PAR. In Chapter II, secondary analyses of the published true-belief literature revealed that children failed several types of true-belief tasks. Chapters III through IX describe new empirical data collected across multiple studies between 2003 and 2014 from 580 children aged 4-7 years, as well as from a small sample of 14 adults. Participants were recruited from the Phoenix, Arizona metropolitan area. All participants were native English-speakers. Children were recruited from university-sponsored and community preschools and daycare centers, and from hospital maternity wards. Adults were university students who participated to partially fulfill course requirements for research participation. Sociometric data were collected only in Chapter IX, and are fully reported there. In Chapter III, minor alterations in task procedures produced wide variations in children's performance in 3-option false-belief tasks. In Chapter IV, we report findings which show that the developmental lag between children's understanding ignorance and understanding false belief is longer than the lag reported in previous studies. In Chapter V, children did not distinguish between agents who have false beliefs versus agents who have no beliefs. In Chapter VI, findings showed that children found it no easier to reason about true beliefs than to reason about false beliefs. In Chapter VII, when children were asked to justify their correct answers in false-belief tasks, they did not reference agents' false beliefs. Similarly, in Chapter VIII, when children were asked to explain agents' actions in false-belief tasks, they did not reference agents' false beliefs. In Chapter IX, children who were identified as using PAR differed from children who understood beliefs along three dimensions-in levels of social development, inhibitory control, and kindergarten adjustment. Although the findings need replication and additional studies of alternative interpretations, the collection of results reported in this monograph challenges the prevailing view that representational ToM is in place by the end of the preschool years. Furthermore, the pattern of findings is consistent with the proposal that PAR is the developmental precursor of representational ToM. The current findings also raise questions about claims that infants and toddlers demonstrate ToM-related abilities, and that representational ToM is innate.

A single treatment approach will never be sufficient to address the diversity of individuals with substance use disorders (SUDs). SUDs have historically defied definition through simple characterizations or models, and no single characterization has led to the development of broadly effective interventions. The range of dimensions of heterogeneity among individuals with SUDs, including severity of the disorder, type of substance, and issues that frequently co-occur, underscores the need for highly tailored approaches. Personalized medicine for individuals with SUDs will require two major developments. First, given the diversity of individuals with SUDs, multivariate phenotyping is needed to identify the particular features driving addictive processes in a given individual. Second, a wider range of interventions that directly target core mechanisms of addiction and the problems that co-occur with them is needed. As clinicians cannot be expected to master the full range of interventions that may target these core processes, developing interventions that can be delivered easily, flexibly, and systematically via technology will facilitate the ability to truly tailor them to this highly complex and challenging population. One such technology-delivered intervention, Computer-Based Training for Cognitive Behavioral Therapy (CBT4CBT), is used as an example to illustrate a vision for the future of highly tailored interventions for individuals with SUDs.

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).

Objectives Screening, Brief Intervention, and Referral to Treatment (SBIRT) has demonstrated efficacy for addressing unhealthy alcohol use in primary care, yet recent research indicates weaker efficacy for drug use as well as very limited success in referral to specialty care for patients with substance use disorder (SUD). Technology-based interventions for SUD delivered in primary care settings are a potential strategy of efficiently delivering treatment to those who need it. Methods We conducted a randomized clinical trial evaluating feasibility, satisfaction, and substance use outcomes for 58 individuals with SUD. Participants being treated in a primary care practice which provides integrated addiction treatment were randomized to standard care or standard care plus access to a web-based SUD intervention (computer-based training in cognitive behavioral therapy, or CBT4CBT). Self-reported substance use and urine toxicology screens were assessed at 8 weeks after randomization. Results Uptake of CBT4CBT in this setting was high; 77% of those assigned to this condition accessed the program at least once; of those, 77% completed all 7 modules. Satisfaction with the program was very high. Participants reported >90% days abstinent for all classes of drugs; with no significant differences between conditions. Conclusions This study demonstrates feasibility of implementing technology-based treatments in primary care settings to address weak follow-through with the referral component of SBIRT. The overall positive outcomes in this specialized, integrated treatment setting may have undercut the ability to demonstrate differential effects on substance use; results suggest evaluation in less specialized primary care settings is warranted. Trial registration clinicaltrials.gov NCT03013478.

ObjectivesCombined smoking and heavy drinking is a significant health burden. Varenicline, an efficacious tobacco pharmacotherapy that also shows promise for drinking, has yielded mixed results among heavy-drinking smokers. This pilot study investigated integrated tobacco and alcohol counselling plus varenicline for this vulnerable group.DesignTwelve-week parallel, randomized controlled pilot trial of two behavioural interventions in combination with open-label varenicline. Participants were randomized using computer-generated tables, stratified by sex.SettingOutpatient academic medical centre research clinic.ParticipantsVolunteers who reported smoking and heavy drinking and sought tobacco or alcohol treatment (N = 26).Intervention(1) Integrated tobacco + alcohol counselling (INT; n = 13) or (2) counselling focused on their presenting concern (i.e., tobacco or alcohol) (SINGLE; n = 13), plus varenicline (2 mg) for 12 weeks.Main outcomesFeasibility/acceptability, smoking quit rates and heavy drinking.ResultsINT feasibility/acceptability was high among men but not women. More participants quit smoking in INT than SINGLE. This outcome was only in men, not significant, but had a medium effect size. Both conditions yielded significant drinking reductions.ConclusionIntegrated tobacco and alcohol behavioural counselling plus varenicline may be feasible and promote smoking cessation among men who smoke and drink heavily, but a larger sample is needed to replicate this finding.

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.

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.

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.

Introduction: Opioid use disorder (OUD) has risen globally and is exerting an enormous toll on public health in many countries, particularly in the United States (US). Buprenorphine (BUP) has become one of the mainstays of pharmacological treatment for OUD and newer delivery methods have been developed to improve its effectiveness in treatment. Areas covered: We provide a review of BUP products available for OUD, with a focus on the newer long-acting formulations. A literature search was conducted using PubMed, Google Scholar, and ClinicalTrials.gov to find randomized clinical trials of long-acting BUP products. Four randomized clinical trials were found: two with BUP implant and two with subcutaneous injectable BUP. Expert opinion: In these clinical trials, new BUP formulations were found to be non-inferior to sublingual (SL) BUP and more effective than placebo in reducing opioid use. Longer-acting formulations can improve flexibility in dosing but superiority over existing SL BUP with regards to outcomes needs to be ascertained. There is a need for more comparative studies between longer-acting BUP formulations and currently available SL BUP. Future studies should also include other clinically meaningful outcomes such as quality of life measures, long-term remission rates, and cost-effectiveness.

Background and objectives Concurrent use of cocaine and opioids is a persistent and challenging problem, particularly within methadone maintenance settings, and there are no approved pharmacotherapies for this population. Galantamine, a cholinesterase inhibitor, was found in a randomized clinical trial to reduce cocaine use among methadone-maintained individuals who were also cocaine dependent. Because of the potential of galantamine to reduce multiple drugs of abuse, it may also reduce opioid use. Methods We conducted a secondary analysis of a randomized, double-blind, placebo-controlled trial of 120 methadone-maintained individuals with concurrent cocaine dependence. Participants were randomized to galantamine or placebo in a 12-week trial with a 6-month follow-up (97% of intention to treat sample reached for final follow-up). Results There was a significant main effect for galantamine over placebo on percent of urine specimens that were negative for opioids, both within treatment (77% for galantamine vs 62% for placebo, F = 5.0, P = 0.027) and through a 6-month follow-up (81% vs 59%, respectively, F = 10.8, P = 0.001). This effect was seen regardless of whether participants used nonprescribed opioids during the baseline period. Galantamine effects were seen early in treatment, with participants in placebo submitting the first opioid-positive urine specimen significantly sooner than participants in galantamine (median day 15 vs 53, Wilcoxon = 5.7, P = 0.02). Conclusions and scientific significance If these results are supported in future trials, galantamine may hold promise across multiple drugs of abuse, including opioids. (Am J Addict 2019;28:238-245).

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.

Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment.The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment.Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance?High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

Background Although behavioral treatment for cocaine use disorders is common, the use of cognitive neuroscience methods to investigate these treatments' mechanisms of action remains limited. Cognitive control (e.g., as measured by the Stroop task) has been proposed to be central to cocaine-use disorders, including treatment response. Methods Participants were methadone-maintained, cocaine-dependent individuals who were participating in a randomized clinical trial (RCT) of 8 weeks of treatment for cocaine-use disorder and randomized to outpatient treatment as usual (TAU) or computer-based cognitive-behavioral therapy (CBT4CBT) plus TAU. Participants completed fMRI Color-Word Stroop task at beginning-of-treatment (N = 19) and post-treatment (N = 10). Analyses assessed correlations between beginning-of-treatment Stroop effect with methadone dose or within-treatment cocaine abstinence, change in Stroop-effect at post- versus beginning-of-treatment, and correlations between ‘change in Stroop effect’ with methadone dose or within-treatment cocaine abstinence. Results Higher methadone dose was associated with higher beginning-of-treatment Stroop-related activity in the declive, culmen, and lingual gyrus. Stroop-related activity was reduced at post-treatment relative to beginning-of-treatment in the medial frontal gyrus/cingulate gyrus and thalamus/midbrain/culmen. Greater reduction in Stroop-related activity was associated with better within-treatment abstinence. Conclusions Diminished Stroop-related activity following treatment may be consistent with improved efficiency of cognitive-control-related activity. Although preliminary, this study is the first to demonstrate a relationship between better treatment outcomes (lower cocaine use during treatment) and greater reduction in Stroop-related activity at post- versus beginning-of-treatment in cocaine users. These findings extend prior work.

Objective:Opioid use disorder (OUD) in the United States has surged, with an estimated 2.5 million needing treatment. The aim of this article is to provide a clinical overview of the key pharmacolo...

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.

Cognitive impairments are associated with poor outcomes when treating cocaine dependent patients, but behavioral interventions to mitigate this impact have not been developed. In this Stage 1A/1B treatment development study, several compensatory strategies (e.g., content repetition, daily logs, diaries, visual presentation) were combined to create a modified cognitive behavioral therapy (M-CBT) for treating cocaine dependence. Initially, a select group of therapists, neuropsychology experts, and patients were asked to provide input on early drafts of the treatment manual and companion patient workbook. After an uncontrolled small trial (N = 15) and two rounds of manual development (Stage 1A), a pilot randomized clinical trial (N = 102) of cocaine dependent outpatients with and without cognitive impairments was conducted (Stage 1B). Participants were randomized to M-CBT (N = 52) or CBT (N = 50). Both treatments were individually delivered over 12 weeks with assessments conducted at baseline, end-of-treatment, and 3-month follow-up. The primary outcome was frequency of cocaine use, measured by number of days used in the prior 7 days. Participants in the two treatment groups did not differ significantly on drug use reduction or retention in treatment. However, among participants who completed at least 9 weeks of treatment, those in M-CBT showed a trend toward greater reduction in cocaine use compared to those in the CBT group. M-CBT is feasible for impaired and nonimpaired cocaine dependent participants. However, M-CBT treatment did not show significant superiority over standard CBT in the present sample. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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.

Introduction Despite the effectiveness of cognitive behavioral therapy (CBT) for treatment of substance use disorder, dissemination to clinical practice is limited due to a range of barriers (e.g., time, cost). Computer-based training for cognitive behavioral therapy (CBT4CBT) offers a feasible and cost-effective opportunity to improve the quality and reach of SUD treatment. Research to date has supported the effectiveness of CBT4CBT in outpatient settings; however, research has not yet tested it in residential treatment. Methods The current study evaluated the feasibility of CBT4CBT as an adjunct to residential treatment in a sample of women with SUDs using a two-arm pilot RCT comparing women randomized to either standard residential treatment plus access to the CBT4CBT program (N = 34) or residential treatment alone (TAU; N = 29). Assessments occurred at baseline, discharge from residential care, and at 4- and 12-weeks post-discharge. The study compared the two groups over the 12-week follow-up period on relapse to any substance (Y/N), relapse to primary substance (Y/N), and days of use using chi-square for categorical and t-tests for continuous measures. The study team also performed a Kaplan-Meier analysis to compare the two groups on time to relapse. Results Demographically, the sample was predominantly African American (79.4%), with a mean age of 41.2 years (SD = 12.1). Although the current study was not powered for statistical significance, findings were in the predicted direction, with women in the CBT4CBT group reporting lower likelihood of relapse, longer time to relapse, and fewer days of substance use in the follow-up period compared to women in TAU. Conclusions This study expands the current literature supporting the use of CBT4CBT in outpatient settings. While a fully powered trial should confirm our findings, the current study provides benchmark data on the use of CBT4CBT in residential treatment for women with SUDs.

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 Black adults with substance use disorders (SUDs) experience health care disparities, including access to and retention in treatment. The Black church is a trusted institution in the Black community and could be a novel setting for providing SUD treatment. Method We conducted a nonrandomized feasibility study evaluating (1) whether it was possible to conduct a clinical trial of SUD treatment in this setting, (2) whether an adequate number of individuals with SUDs would participate in technology-based treatment in this setting, and (3) whether an adequate number of individuals would be retained in this setting. We evaluated computer-based training for cognitive behavioral therapy (CBT4CBT), with modifications that the church-based health advisors (CHAs), who delivered the intervention within the church, made. Results Participants were 40 Black adults, all of whom met DSM-5 criteria for a current SUD, (55% severe). The mean number of sessions completed was 6.8 and 31 completed all 7 sessions of CBT4CBT. Both self-reports and weekly urine toxicology screens indicated reduction in substance use over time. Conclusion We demonstrated feasibility, as we were able to (1) collect weekly data and protect participant confidentiality, (2) recruit an adequate number of individuals with SUD, with (3) high uptake and retention of an adapted CBT4CBT in the Black church. If demonstrated to be effective in a future randomized clinical trial, delivery of technology-based treatments in the Black church may prove a promising, easily disseminable strategy to provide evidence-based interventions to an underserved and undertreated population.

Objective Contingency management (CM) interventions that reinforce attendance have rarely been evaluated in terms of reducing drug use. Using a sequential randomized design, this study examined the efficacy of three attendance CM conditions compared to usual care (UC) on drug use outcomes. It evaluated whether the duration (6 vs. 12 weeks) and timing (early vs. later treatment) of CM delivery impact treatment response. Method Upon initiating outpatient treatment, patients with cocaine use disorders (N = 360) were randomized to UC or CM for attending treatment for 6 weeks. At week 6, patients (n = 308) were rerandomized to UC or CM for another 6 weeks, with assignment stratified on current functioning. Samples were screened for illicit drugs twice weekly for 12 weeks. Results Patients randomized to CM at both time-points attended more sessions and achieved more abstinence than those never randomized to CM. Relative to UC, receiving attendance CM in weeks 1-6 only was not efficacious, but those receiving attendance CM in weeks 7-12 only evidenced some benefits compared to those who never received CM. Twelve weeks of attendance CM was more efficacious than 6 weeks. No between-groups differences in drug use were noted at follow-ups, but days attended treatment and proportion negative samples during treatment were associated with long-term cocaine abstinence. Conclusions Attendance-based CM increases treatment participation and reduces drug use, with beneficial effects noted when CM is delivered over longer durations and during later phases of outpatient care. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD. The cholinergic system includes enzymes that synthesize and degrade ACh and receptors that mediate the effects of ACh. ACh is involved in many central nervous system functions that are critical to the development and maintenance of OUD, such as reward and cognition. Medications that target the cholinergic system have been approved for the treatment of Alzheimer's disease, tobacco use disorder, and nausea. Clinical and preclinical studies suggest that medications such as cholinesterase inhibitors and scopolamine, which target components of the cholinergic system, show promise for the treatment of OUD and further investigations are warranted.

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.

Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n = 53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)—a recently developed, whole-brain approach—was used to identify pretreatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Posttreatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared with healthy subjects (n = 38). CPM identified an opioid abstinence network (p = 0.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode, and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at posttreatment related to abstinence at 6-month follow-up (p

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 Cognitive-behavior therapy (CBT) for substance use disorder is empirically supported, and may be associated with change in affect over time. OBJECTIVES Understanding the role of affect in cocaine use disorder could help to improve CBT outcomes. METHODS This secondary analysis included 140 adults with cocaine use disorder, 57.9% female, drawn from two randomized controlled studies of web-based cognitive-behavior therapy who completed the Positive and Negative Affect Scale (PANAS) before and during treatment. RESULTS In mixed-effects regression models, baseline negative affect (NA) scores were not associated with self-reported cocaine use during treatment, but baseline PA scores were associated with less frequent cocaine use (β = -0.04, p = .02). During treatment, NA scores reduced over time in CBT and treatment as usual (β = -0.27, 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.

Background Tobacco use is often initiated during adolescence and continued into adulthood despite desires to quit. A better understanding of the neural correlates of abstinence from smoking in adolescents may inform more effective smoking cessation interventions. Neural reward systems are implicated in tobacco use disorder, and adolescent smokers have shown reduced reward-related ventral striatal activation related to increased smoking. Methods The current study evaluated nondrug reward anticipation in adolescent smokers using a monetary incentive delay task in fMRI pre- and post- smoking cessation treatment ( n = 14). This study tested how changes in neural responses to reward anticipation pre- to post-treatment were related to reduced smoking. An exploratory analysis in a larger sample of adolescents with only pre-treatment fMRI ( n = 28) evaluated how neural responses to reward anticipation were related to behavioral inhibition and behavioral activation scales. Results Adolescent smokers showed pre- to post-treatment increases in reward anticipation-related activity in the bilateral nucleus accumbens and insula, and medial prefrontal cortex, and greater increases in reward anticipation-related activity were correlated with larger percent days of smoking abstinence during treatment. Conclusions These findings suggest that reduced smoking during smoking cessation treatment is associated with a “recovery of function” in frontostriatal responses to nondrug reward anticipation in adolescent smokers, although comparison with a developmental control group of adolescent nonsmokers is warranted.

Alterations in neural structure have been reported in both cocaine-use disorder and gambling disorder, separately, suggesting similarities across addiction diagnoses. Individual variation in neural structure has also been associated with impulsivity, a dimensional construct implicated in addictions. This study combines categorical (diagnosis-based) and dimensional (transdiagnostic) approaches to identify neural structural alterations linked to addiction subtypes and trait impulsivity, respectively, across individuals with gambling disorder (n = 35), individuals with cocaine-use disorder (n = 37) and healthy comparison individuals (n = 37). High-resolution T1-weighted data were analyzed using modulated voxel-based morphometry (VBM). Statistical analyses were conducted using whole-brain general-linear models, corrected for family-wise error (pFWE

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.

No pharmacotherapies are approved for the treatment of cocaine use disorder (CUD). Galantamine, a cholinesterase inhibitor, has shown initial promise for cocaine use reduction in methadone-maintained individuals with CUD and cognitive improvement in abstinent individuals with past CUD. However, galantamine has not previously tested in individuals with current CUD and no comorbid opioid use disorder or methadone maintenance. The goal of this 13-week, double-blind, placebo-controlled, randomized controlled trial was to test the efficacy of galantamine (8 mg or 16 mg/day; extended release (ER)) for reducing cocaine use and improving cognitive function in individuals with cocaine use disorder (CUD). Ninety-three treatment-seeking cocaine users were randomized to placebo (n = 32), 8 mg/day galantamine (n = 31) or 16 mg/day galantamine (n = 30). The medication was well-tolerated with minimal reports of side-effects. However, there were no significant treatment group differences in cocaine use outcomes (as measured by self-report or urines). The 16 mg galantamine group had a greater improvement in working memory capacity (Backwards Digit Span), but there were no other significant treatment group differences on key cognitive outcomes. These findings did not provide support for the efficacy of galantamine as a treatment for cocaine use in this sample of individuals with CUD.