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Although reward processing appears altered in addiction, few studies track neurofunctional changes following treatment or relate these to measures of reduced drug use. The current study examined neurofunctional alterations in reward processing in cocaine dependence (CD) pretreatment and posttreatment to determine whether these changes relate to clinically meaningful outcome indicators. Treatment-seeking CD outpatients (N=29) underwent functional magnetic resonance imaging while performing a monetary incentive delay task (MIDT) pretreatment and posttreatment. The MIDT parses anticipatory from outcome phases of reward/loss processing. Abstinence indicators (negative urines, days abstinent from cocaine during follow-up) were collected throughout treatment and up to 1 year later. Healthy control (HC) participants (N=28) were also scanned twice with the MIDT. Relative to pretreatment, at posttreatment CD participants demonstrated increased anticipatory reward activity in the midbrain, thalamus, and precuneus (pFWE<0.05). Increased midbrain activity correlated with cocaine abstinence during the 1-year follow-up. Ventral striatal (VS) activity during loss anticipation correlated negatively with negative urine screens. HC group test-retest results showed decreased ventromedial prefrontal cortex activity during winning outcomes. CD-HC group-by-time differences revealed increased left inferior frontal gyrus activity in the CD group during anticipatory phases at posttreatment. In CD participants, increased posttreatment activity in dopamine-innervated regions suggests lowered thresholds in anticipatory signaling for non-drug rewards. Midbrain and VS responses may represent biomarkers associated with CD abstinence. Abstinence-related neurobiological changes occur in similar regions implicated during active use and may possibly be used to track progress during short- and long-term recovery.

Background: Few measures exist to examine therapist empathy as it occurs in session. Aims: A 9-item observer rating scale, called the Therapist Empathy Scale (TES), was developed based on Watson's (1999) work to assess affective, cognitive, attitudinal, and attunement aspects of therapist empathy. The aim of this study was to evaluate the inter-rater reliability, internal consistency, and construct and criterion validity of the TES. Method: Raters evaluated therapist empathy in 315 client sessions conducted by 91 therapists, using data from a multi-site therapist training trial (Martino et al., 2010) in Motivational Interviewing (MI). Results: Inter-rater reliability (ICC = .87 to .91) and internal consistency (Cronbach's alpha = .94) were high. Confirmatory factor analyses indicated some support for single-factor fit. Convergent validity was supported by correlations between TES scores and MI fundamental adherence (r range .50 to .67) and competence scores (r range .56 to .69). Discriminant validity was indicated by negative or nonsignificant correlations between TES and MI-inconsistent behavior (r range .05 to −.33). Conclusions: The TES demonstrates excellent inter-rater reliability and internal consistency. Results indicate some support for a single-factor solution and convergent and discriminant validity. Future studies should examine the use of the TES to evaluate therapist empathy in different psychotherapy approaches and to determine the impact of therapist empathy on client outcome.

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.

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

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 pharmacological and behavioral treatments for OUD.Methods:A nonsystematic review of the literature was conducted to investigate OUD treatments, including their mechanism of action, efficacy, clinical guidelines in the United States, and consideration of frequently occurring comorbid conditions.Results:Food and Drug Administration (FDA)–approved pharmacotherapies for OUD include methadone, buprenorphine, and naltrexone, each of which has different actions on opioid receptors. Although these medications all show efficacy in some dosages and formulations, barriers to accessibility may be most pronounced for methadone, whereas treatment retention poses greater challenges for naltrexone and, to a lesser extent, buprenorphine. Lofexidine, an α2-adrenergic agonist, has recently been approved by the FDA for treatment of opioid withdrawal symptoms. OUD is commonly treated with medication-assisted treatment (MAT), which offers pharmacotherapy in the context of counseling and/or behavioral treatments. Behavioral therapies, rarely offered as stand-alone treatments for OUD, are generally used in the context of MAT, in structured settings or to prevent relapse after detoxification and stabilization. The aim of behavioral interventions is to improve medication compliance and target problems not addressed with medication alone. Individuals with OUD commonly have other comorbid psychiatric and substance use conditions, which are not exclusionary for initiating MAT but should be carefully evaluated and monitored because they may reduce treatment effectiveness.Conclusions:MAT is the first-line treatment for patients with OUD and should be provided in combination with behavioral interventions. Treatment retention remains challenging in this population. Future studies should focus on approaches that will serve the complex needs of patients with OUD, including those with comorbid psychiatric and substance use conditions.

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.

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.

Aim. To evaluate outcomes 1 year after cessation of treatment for cocaine‐ and alcohol‐dependent individuals. Design. Randomized controlled trial. Setting. Urban substance abuse treatment center. Participants. Ninety‐six of 122 subjects randomized to treatment. Interventions. One of five treatments delivered over 12 weeks. Cognitive‐behavioral treatment (CBT) plus disulfiram; Twelve‐Step facilitation (TSF) plus disulfiram; clinical management (CM) plus disulfiram; CBT without disulfiram; TSF without disulfiram. Measurements. Percentage of days of cocaine and alcohol use during follow‐up, verified by urine toxicology screens and breathalyzer tests. Results. First, as a group, participants reported significant decreases in frequency of cocaine, but not alcohol, use after the end of treatment. Secondly, the main effects of disulfiram on cocaine and alcohol use were sustained during follow‐up. Finally, initiation of abstinence for even brief periods of time within treatment was associated with significantly better outcome during follow‐up. Conclusions. These findings support the efficacy of disulfiram with this challenging population and suggest that comparatively brief treatments that facilitate the initiation of abstinence may have long‐term benefits.

Cannabis is among the most frequently abused substances in the United States. Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response. Therefore, we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up. Cannabis-dependent males (N=20) completed a functional magnetic resonance imaging (fMRI) cognitive-control (Stroop) task before a 12-week randomized controlled trial of cognitive-behavioral therapy and/or contingency management. A healthy-comparison group (N=20) also completed the fMRI task. Cannabis use was assessed by urine toxicology and self-report during treatment, and by self-report across a 1-year follow-up period (N=18). The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions, including those strongly implicated in cognitive-control and addiction-related processes (eg, dorsolateral prefrontal cortex and ventral striatum). The groups did not differ significantly in response times (cannabis-dependent, N=12; healthy-comparison, N=14). Within the cannabis-dependent group, greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment. Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up. These data suggest that lower cognitive-control-related neural activity in classic 'control' regions (eg, dorsolateral prefrontal cortex and dorsal anterior cingulate) and classic 'salience/reward/learning' regions (eg, ventral striatum) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up. Clinically, results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence.

Aims: Cocaine use by patients on methadone maintenance treatment is a widespread problem and is associated with a poorer prognosis. Recent studies have evaluated disulfiram as a treatment for individuals with comorbid alcohol and cocaine abuse. We evaluated the efficacy of disulfiram for cocaine dependence, both with and without co‐morbid alcohol abuse, in a group of methadone‐maintained opioid addicts. Design: Randomized double‐blind, placebo‐controlled trial. Setting: Urban methadone maintenance clinic. Participants: Sixty‐seven cocaine‐dependent, methadone‐maintained, opioid‐dependent subjects (52% female; 51% Caucasian). Intervention: Study medication, either disulfiram or placebo, was placed directly in the methadone to ensure compliance for 12 weeks. Measurements: Primary outcome measures included weekly assessments of the frequency and quantity of drug and alcohol use, weekly urine toxicology screens and breathalyzer readings. Findings: Disulfiram treated subjects decreased the quantity and frequency of cocaine use significantly more than those treated with placebo. Alcohol use was minimal for all subjects regardless of the medication. Conclusions: Disulfiram may be an effective pharmacotherapy for cocaine abuse among methadone‐maintained opioid addicts, even in those individuals without co‐morbid alcohol abuse. Disulfiram inhibits dopamine beta‐hydroxylase resulting in an excess of dopamine and decreased synthesis of norepinephrine. Since cocaine is a potent catecholamine re‐uptake inhibitor, disulfiram may blunt cocaine craving or alter the \"high\", resulting in a decreased desire to use cocaine.