Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling.

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 < 0.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and nonresponders. These data indicate dissociable anatomical substrates of opioid vs. cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

Computer-based training for cognitive behavioral therapy for Spanish-speaking substance users: adaptation and satisfaction.

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 telenovela to teach monolingual Spanish-speaking adults who have migrated to the United States to recognize triggers; avoid these situations; and cope more effectively with the consequences of substance use. Participants endorsed high levels of satisfaction with the program content and found the material to be easy to understand and relevant to their life experiences.

Religiosity and Spirituality in Latinx Individuals with Substance Use Disorders: Association with Treatment Outcomes in a Randomized Clinical Trial.

Although many studies have examined religiosity as a protective factor for substance use, few have considered its relationship to treatment outcomes among Latinx adults. Using data from 89 individuals participating in a randomized clinical trial evaluating a culturally adapted Spanish-language version of web-based cognitive behavioral therapy (CBT4CBT-Spanish) for substance use, we evaluated the relationship between religiosity, as measured by the Religious Background and Behavior questionnaire, and treatment outcomes. Overall, there were few significant correlations between religiosity scores and treatment outcomes. Past-year religiosity was positively correlated with one measure of abstinence for those randomized to CBT4CBT-Spanish, but this did not persist during a six-month follow-up period. Findings suggest that religiosity may be associated with short-term abstinence outcomes among Latinx adults receiving a culturally adapted cognitive behavioral therapy treatment. However, additional research is needed with larger and more heterogenous Latinx populations.

Cognitive-Behavioral Interventions Targeting Alcohol or Other Drug Use and Co-Occurring Mental Health Disorders: A Meta-Analysis.

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.

Double-Blind Placebo-Controlled Trial of Galantamine for Methadone-Maintained Individuals With Cocaine Use Disorder: Secondary Analysis of Effects on Illicit Opioid Use.

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).

Randomized pilot trial of Web-based cognitive-behavioral therapy adapted for use in office-based buprenorphine maintenance.

Background: Despite the clear success of office-based buprenorphine treatment in increasing availability of effective treatment for opioid use disorder, constraints on its effectiveness include high attrition and limited high-quality behavioral care in many areas. Web-based interventions may be a novel strategy for providing evidence-based behavioral care to individuals receiving office-based buprenorphine maintenance. This report describes modification and initial pilot testing of Web-based training in cognitive-behavioral therapy (CBT4CBT) specifically for use with individuals in office-based buprenorphine. Methods: Twelve-week randomized pilot trial evaluating effects of CBT4CBT-Buprenophine in retaining participants and reducing drug use with respect to standard office-based buprenorphine alone was carried out. Twenty individuals meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) criteria for current opioid use disorder were randomized to standard buprenorphine treatment or buprenorphine plus access to CBT4CBT-Buprenorphine. Results: There were promising findings regarding rates of urine toxicology screens negative for opioids (91% versus 64%; P = .05, effect size d = 0.88) and all drugs (82% versus 30%; P = .004, d = 1.2). Individuals randomized to CBT4CBT-Buprenorphine completed a mean of 82.6 (SD = 4.4) days of treatment (of a possible 84) compared with 68.6 (SD = 32.6) for those assigned to standard buprenorphine treatment. Conclusions: Although preliminary and limited by the small sample size, this trial suggests the feasibility and promise of validated, Web-based interventions, tailored for this specific patient population, for improving outcomes in office-based buprenorphine.

Culturally Adapted, Web-Based Cognitive Behavioral Therapy for Spanish-Speaking Individuals With Substance Use Disorders: A Randomized Clinical Trial.

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.

Change in DSM-5 Alcohol Use Disorder Criteria Count and Severity Level as a Treatment Outcome Indicator: Results from a Randomized Trial.

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 < 0.01], but no significant interactions between time and treatment condition. Fewer total criteria endorsed, as well as achieving at least a 2-level reduction in AUD severity category at end-of-treatment, were associated with better outcomes during follow-up. Chi-square results indicated a greater proportion of individuals assigned to TAU+CBT4CBT had at least a 2-level reduction in severity category compared to TAU, at trend-level significance [χ2 (2, 54) = 5.13, p = 0.07], consistent with primary alcohol use outcomes in the main trial. CONCLUSIONS: This is the first study to demonstrate change in DSM-5 AUD total criteria count, as well as severity category, in a randomized clinical trial. These findings offer support for their use as a potential clinically meaningful outcome indicator.

Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions.

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 < .05). Categorical analyses indicated a main effect of diagnostic group on prefrontal (dorsal anterior cingulate and ventromedial prefrontal cortex) gray matter volumes (GMVs), involving decreased GMVs among cocaine-use disorder participants only. Dimensional analyses indicated a negative association between trait impulsivity and cortical (insula) and subcortical (amygdala and hippocampus) GMVs across all participants. Conjunction analysis indicated little anatomical overlap between regions identified as differentiating diagnostic groups and regions covarying with impulsivity. These data provide first evidence of neural structural differences between gambling disorder and an illicit substance-use disorder. They further indicate dissociable effects of diagnostic groupings and trait impulsivity on neural structure among individuals with behavioral and drug addictions. Study findings highlight the importance of considering both categorical and dimensional (e.g. Research Domain Criteria; RDoC) analysis approaches within the context of addictions research.

Positive and negative affect in cocaine use disorder treatment: Change across time and relevance to treatment outcome.

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 (ß = -0.04, p = .02). During treatment, NA scores reduced over time in CBT and treatment as usual (ß = -0.27, p < .01), although PA scores did not change. Higher weekly NA scores were associated with weekly cocaine use (ß = .02, SE = .01, t(746.15) = 2.37, p = .02), although weekly PANAS PA scores were not associated with weekly cocaine use. DISCUSSION AND CONCLUSIONS: Results indicated that individuals with higher baseline PA were more likely to abstain from cocaine use during treatment, even when controlling for baseline cocaine use frequency. Although baseline NA was not associated with cocaine use, NA during treatment was associated with greater cocaine use. SCIENTIFIC SIGNIFICANCE: PA at baseline and NA during treatment were associated with cocaine use. If findings are replicated, treatment developers may wish to include treatment interventions to boost early PA and reduce NA throughout treatment. (Am J Addict 2018;XX:1-8).