Structural brain changes associated with cocaine use and digital cognitive behavioral therapy in cocaine use disorder treatment.

Background: Few studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization. Methods: In this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo). Results: Irrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV. Conclusions: These results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.

Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.

BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine. METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38). RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study. DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.

Efficacy of Integrating the Management of Pain and Addiction via Collaborative Treatment (IMPACT) in Individuals With Chronic Pain and Opioid Use Disorder: Protocol for a Randomized Clinical Trial of a Digital Cognitive Behavioral Treatment.

BACKGROUND: Chronic pain is common among individuals with opioid use disorder (OUD) who are maintained on medications for OUD (MOUD; eg, buprenorphine or methadone). Chronic pain is associated with worse retention and higher levels of substance use. Treatment of individuals with chronic pain receiving MOUD can be challenging due to their increased clinical complexity. Given the acute and growing nature of the opioid crisis, MOUD is increasingly offered in a wide range of settings, where high-quality, clinician-delivered, empirically validated behavioral treatment for chronic pain may not be available. Therefore, digital treatments that support patient self-management of chronic pain and OUD have the potential for wider implementation to fill this gap. OBJECTIVE: This study aims to evaluate the efficacy of Integrating the Management of Pain and Addiction via Collaborative Treatment (IMPACT), an interactive digital treatment program with asynchronous coach feedback, compared to treatment as usual (TAU) in individuals with chronic pain and OUD receiving MOUD. METHODS: Adult participants (n=160) receiving MOUD and reporting bothersome or high-impact chronic pain will be recruited from outpatient opioid treatment programs in Connecticut (United States) and randomized 1:1 to either IMPACT+TAU or TAU only. Participants randomized to IMPACT+TAU will complete an interactive digital treatment that includes 9 modules promoting training in pain and addiction coping skills and a progressive walking program. The program is augmented with a weekly personalized voice message from a trained coach based on daily participant-reported pain intensity and interference, craving to use opioids, sleep quality, daily steps, pain self-efficacy, MOUD adherence, and engagement with IMPACT collected through digital surveys. Outcomes will be assessed at 3, 6, and 9 months post randomization. The primary outcome is MOUD retention at 3 months post randomization (ie, post treatment). Secondary outcomes include pain interference, physical functioning, MOUD adherence, substance use, craving, pain intensity, sleep disturbance, pain catastrophizing, and pain self-efficacy. Semistructured qualitative interviews with study participants (n=34) randomized to IMPACT (completers and noncompleters) will be conducted to evaluate the usability and quality of the program and its outcomes. RESULTS: The study has received institutional review board approval and began recruitment at 1 site in July 2022. Recruitment at a second site started in January 2023, with a third and final site anticipated to begin recruitment in January 2024. Data collection is expected to continue through June 2025. CONCLUSIONS: Establishing efficacy for a digital treatment for addiction and chronic pain that can be integrated into MOUD clinics will provide options for individuals with OUD, which reduce barriers to behavioral treatment. Participant feedback on the intervention will inform updates or modifications to improve engagement and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05204576; https://clinicaltrials.gov/ct2/show/NCT05204576. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54342.

Promoting alcohol treatment engagement post-hospitalization with brief intervention, medications and CBT4CBT: protocol for a randomized clinical trial in a diverse patient population.

BACKGROUND: Alcohol use disorder (AUD) commonly causes hospitalization, particularly for individuals disproportionately impacted by structural racism and other forms of marginalization. The optimal approach for engaging hospitalized patients with AUD in treatment post-hospital discharge is unknown. We describe the rationale, aims, and protocol for Project ENHANCE (ENhancing Hospital-initiated Alcohol TreatmeNt to InCrease Engagement), a clinical trial testing increasingly intensive approaches using a hybrid type 1 effectiveness-implementation approach. METHODS: We are randomizing English and/or Spanish-speaking individuals with untreated AUD (n = 450) from a large, urban, academic hospital in New Haven, CT to: (1) Brief Negotiation Interview (with referral and telephone booster) alone (BNI), (2) BNI plus facilitated initiation of medications for alcohol use disorder (BNI + MAUD), or (3) BNI + MAUD + initiation of computer-based training for cognitive behavioral therapy (CBT4CBT, BNI + MAUD + CBT4CBT). Interventions are delivered by Health Promotion Advocates. The primary outcome is AUD treatment engagement 34 days post-hospital discharge. Secondary outcomes include AUD treatment engagement 90 days post-discharge and changes in self-reported alcohol use and phosphatidylethanol. Exploratory outcomes include health care utilization. We will explore whether the effectiveness of the interventions on AUD treatment engagement and alcohol use outcomes differ across and within racialized and ethnic groups, consistent with disproportionate impacts of AUD. Lastly, we will conduct an implementation-focused process evaluation, including individual-level collection and statistical comparisons between the three conditions of costs to providers and to patients, cost-effectiveness indices (effectiveness/cost ratios), and cost-benefit indices (benefit/cost ratios, net benefit [benefits minus costs). Graphs of individual- and group-level effectiveness x cost, and benefits x costs, will portray relationships between costs and effectiveness and between costs and benefits for the three conditions, in a manner that community representatives also should be able to understand and use. CONCLUSIONS: Project ENHANCE is expected to generate novel findings to inform future hospital-based efforts to promote AUD treatment engagement among diverse patient populations, including those most impacted by AUD. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05338151.

Percentage of negative urine drug screens as a clinically meaningful endpoint for RCTs evaluating treatment for cocaine use.

BACKGROUND: This study examined a threshold based on the percentage of cocaine-negative (CN) urine drug screens (UDS) collected during treatment as a potential meaningful endpoint for clinical trials. We hypothesized that individuals providing at least 75% CN UDS would have better long-term outcomes than those providing less than 75% CN UDS. METHODS: Two separate pooled datasets of randomized clinical trials conducted at different institutions were used for analyses: one composed of eight trials (N = 760) and the other composed of three trials (N = 416), all evaluating behavioral and/or pharmacological treatments for cocaine use. UDS were collected at least once per week (up to three times per week) during the 8- or 12-week treatment period across all trials, with substance use and psychosocial functioning measured up to 12 months following treatment. Chi-squares and ANOVAs compared within-treatment and follow-up outcomes between the groups. RESULTS: Compared to those who did not achieve the threshold, participants who achieved the 75%-CN threshold were retained in treatment longer and had a longer period of continuous abstinence, and were more likely to report problem-free functioning. Additionally, participants who achieved the 75%-CN threshold were more likely to report sustained abstinence and better psychosocial functioning throughout a follow-up period up to 12 months than those who did not achieve the threshold. CONCLUSIONS: A threshold of 75%-CN UDS is associated with short- and long-term clinical benefits. Future clinical trials may consider this a meaningful threshold for defining treatment responders.

Breaking through social determinants of health: Results from a feasibility study of Imani Breakthrough, a community developed substance use intervention for Black and Latinx people.

Racial and ethnic disparities in substance use intervention design, implementation, and dissemination have been recognized for years, yet few intervention programs have been designed and conducted by and for people who use substances. Imani Breakthrough is a two-phase 22-week intervention developed by the community, run by facilitators with lived experience and church members, that is implemented in Black and Latinx church settings. This community-based participatory research (CBPR) approach is a concept developed in response to a call for action from the State of Connecticut Department of Mental Health and Addiction Services (DMHAS) with funding from the Substance Abuse and Mental Health Services Administration (SAMHSA) to address rising rates of death due to opioid overdose, and other negative consequences of substance misuse. After nine months of didactic community meetings, the final design involved twelve weeks of education in a group setting related to the recovery process, including the impact of trauma and racism on substance use, and a focus on citizenship and community participation and the 8 dimensions of wellness, followed by ten weeks of mutual support, with intensive wraparound support and life coaching focused on the social determinants of health (SDOH). We found the Imani intervention was feasible and acceptable, with 42 % of participants retained at 12 weeks. In addition, in a subset of participants with complete data, we found a significant increase in both citizenship scores and dimensions of wellness from baseline to week 12, with the greatest improvements in the occupational, intellectual, financial, and personal responsibility dimensions. As drug overdose rates among Black and Latinx people who use substances continue to increase, it is imperative that we address the inequities in the SDOH that contribute to this disparity gap so that we can develop interventions tailored to the specific needs of Black and Latinx people who use drugs. The Imani Breakthrough intervention shows promise as a community-driven approach that can address these disparities and promote health equity.

The rise and fall of substance use during treatment: Applying recency and expectancy principles to daily substance use patterns.

OBJECTIVE: 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. METHOD: 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 (n = 94; 76% males; Mage = 38; 46% African American, 38% White, 6% multiracial, 10% other; 17% Hispanic). The number of days before/after a therapy session was used to predict daily substance use assessed by weekly self-reports. RESULTS: The models suggested that substance use increased as more days passed after a therapy session (b = 5.23) and then decelerated before the next therapy session (b² = -8.20). The evidence indicated that substance use was less likely on therapy days and the days after therapy. Primary drug type, SUD severity, and treatment condition moderated these findings. CONCLUSIONS: 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) 2023 APA, all rights reserved).

The connection still matters: Therapeutic alliance with digital treatment for alcohol use disorder.

BACKGROUND: A strong cooperative bond between the patient and provider ("therapeutic alliance") is robustly associated with better alcohol use disorder (AUD) treatment outcomes. Although digital treatments for AUD have significant potential, the function of the alliance during digital programs is unclear. We compared the validity of patient-reported measures of the alliance with a digital treatment ("digital alliance") for AUD and the alliance with their clinician ("clinician alliance"). METHODS: We used data from an 8-week, randomized clinical trial of a computerized cognitive behavioral therapy program (CBT4CBT) during outpatient AUD treatment. Treatment conditions included CBT4CBT with minimal clinical monitoring (CBT4CBT + monitor) or with treatment as usual (CBT4CBT + TAU). The digital alliance and clinician alliance were measured with similar versions of the Working Alliance Inventory (WAI). The WAI ratings were completed at the 2nd and 6th treatment sessions. A timeline followback calendar assessed daily alcohol use. Bayesian multilevel models compared the strength of the alliances and tested their associations with future alcohol use. RESULTS: Data from 43 participants were included (age M = 44; 65% male; 51% Black, 40% White, 9% other; 14% Hispanic). The digital alliance ratings had similar internal reliability as the clinician alliance ratings (ω's > 0.90). Differences between digital alliance and clinician alliance ratings were negligible in both treatment conditions (BF01 = 9 and 31). During treatment, within-person increases in the digital alliance and the clinician alliance predicted modest decreases in future drinking to a similar degree (BF01 = 15). Alliance ratings were not associated with future drinking when posttreatment follow-up drinking data were included (BF10 < 3). CONCLUSIONS: The digital alliance with CBT4CBT was comparable to the clinician alliance. The digital alliance and clinician alliance had similar, albeit very small, associations with abstinence during treatment. Future research can explore how the digital alliance develops to improve AUD treatment efficacy.

Modafinil Does Not Reduce Cocaine Use in Methadone-Maintained Individuals.

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Racial and ethnic differences in alcohol, cannabis, and illicit substance use treatment: a systematic review and narrative synthesis of studies done in the USA.

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.

Detecting change in psychiatric functioning in clinical trials for cocaine use disorder: sensitivity of the Addiction Severity Index and Brief Symptom Inventory.

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.

A feasibility study providing substance use treatment in the Black church.

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.

A pilot economic evaluation of computerized cognitive behavioral therapy for alcohol use disorder as an addition and alternative to traditional therapy.

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.

Measurement invariance of the Barratt Impulsiveness Scale across black and white adults with cocaine use disorder.

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, agemean = 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 = 0.073 [90% CI: 0.065-0.080]; CFI = 0.904; TLI = 0.893; SRMR = 0.073) 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 = -0.15, p = .01), but this association only remained in the Black subsample when examined across race (r = 0.28, p < .001). Higher motor impulsiveness was also associated with increased days abstinent from cocaine in the Black subsample only (r = 0.28, p < .001). Nonplanning impulsiveness was associated with lower percentage of treatment days abstinent from cocaine in the White subsample only (r = -0.16, p = .045). These findings 1) provide evidence for a 21-item, two-factor brief BIS that is invariant across Black and White adults with cocaine use disorder, and 2) suggest that BIS impulsivity may be associated with poorer cocaine treatment outcomes among White but not Black adults.

Short- and long-term changes in substance-related coping as mediators of in-person and computerized CBT for alcohol and drug use disorders.

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.

Computerized Cognitive Behavioral Therapy for Substance Use Disorders in a Specialized Primary Care Practice: A Randomized Feasibility Trial to Address the RT Component of SBIRT.

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.

Randomized placebo-controlled trial of galantamine in individuals with cocaine use disorder.

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.

Clinical validation of reduction in cocaine frequency level as an endpoint in clinical trials for cocaine use disorder.

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.

Sociodemographic and clinical outcome differences among individuals seeking treatment for cocaine use disorders. The intersection of gender and race.

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.