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Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of nondrug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The present study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial aimed at developing adaptive interventions for CUD. We examined the relationship between anhedonia and cocaine demand and how these measures were related to cocaine use severity. Participants ( N = 116) were treatment-seeking adults with CUD. All measures were taken at baseline before treatment initiation. Analyses revealed (a) moderate and very strong evidence of relationships between cocaine demand factors (i.e., persistence, amplitude) and anhedonia (PP values ≥ 77.8%); (b) positive association between cocaine demand (both persistence and amplitude) and measures of cocaine use severity, with the exception of one relationship, which was in the opposite direction; and (c) demand amplitude continued to be positively related to cocaine use severity, even when considering anhedonia. Overall, findings from this study indicate cocaine demand relates to cocaine use severity more strongly than anhedonia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting injectable PrEP among sexually active adult PWUD. The data were collected from adult participants (n = 270) residing in Harris County, TX, who self-reported problematic substance use and who reported oral, anal, or vaginal sex in the six months prior to completing the survey. The survey was distributed and completed online via Qualtrics Panels in March of 2022 and included measures of PrEP and HIV knowledge, PrEP stigma, sexual health self-efficacy, experiences of discrimination, health literacy, and medical mistrust. The majority of participants reported circumstances or behaviors that increased their susceptibility to HIV. Findings indicated that PrEP user stereotypes and PrEP anticipated disapproval by others were associated with interest in using daily oral PrEP and willingness to use long acting injectable PrEP. These results provide insight into reasons for low PrEP uptake among PWUD who live in a high HIV prevalence jurisdiction. Implications for HIV prevention intervention are discussed., (© 2024. The Author(s).)

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions., (© 2024 Society for Psychophysiological Research.)

Background: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1., Method: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists., Results: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed., Discussion: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth., (© 2024. The Author(s).)

Background: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse., Methods: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original multimodal pain regimen (intravenous followed by oral acetaminophen, 48-hour celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, as-needed opioid), in a randomized trial conducted from April 2018 to March 2019. A total of 631 enrolled patients were classified either as low- or high-risk via the Opioid Risk Tool. Bayesian analyses evaluated the moderating influence of Opioid Risk Tool risk (high/low) on the effect of Multimodal Analgesic Strategies for Trauma multimodal pain regimen (versus original) on opioid exposure (morphine milligram equivalents/day), opioids prescribed at discharge, and pain scores., Results: Multimodal Analgesic Strategies for Trauma multimodal pain regimen effectively reduced morphine milligram equivalents/day in low- and high-Opioid Risk Tool risk groups. Moderation was observed for opioids at discharge and pain scores; Multimodal Analgesic Strategies for Trauma multimodal pain regimen was effective in the high-risk group only (opioids at discharge: 63% vs 77%, relative risk = 0.86, 95% Bayesian credible interval [0.66-1.08], posterior probability (relative risk <1) = 90%; pain scores: b = 3.8, 95% Bayesian credible interval [3.2-4.4] vs b = 4.0, 95% Bayesian credible interval [3.4-4.6], posterior probability (b <0) = 87%)., Conclusion: This study is the first to show the moderating influence of opioid misuse risk on the effectiveness of an opioid-minimizing multimodal pain regimen. The Opioid Risk Tool was useful in identifying high-risk patients for whom the Multimodal Analgesic Strategies for Trauma multimodal pain regimen is recommended for perioperative pain management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) commonly co-occur and represent a complex, challenging clinical comorbidity. Meta-analytic studies and systematic reviews suggest that trauma-focused treatments are more efficacious than non-trauma focused interventions for co-occurring PTSD/SUD. However, relatively little is known about mental health clinicians' practices or preferences for treating co-occurring PTSD/SUD. The present study aimed to describe the current clinical practices of mental health clinicians who treat PTSD and/or SUD-related conditions and to assess interest in novel integrative treatments for PTSD/SUD., Methods: Licensed mental health clinicians ( N  = 76; M age = 39.59, SD  = 8.14) who treat PTSD and/or SUD completed an anonymous online survey from April 2021 to July 2021., Results: The majority (61.8%) of clinicians reported using integrative treatments for PTSD/SUD. The most commonly used trauma-focused treatments were 1) Cognitive Processing Therapy (CPT: 71.1%) and 2) Prolonged Exposure Therapy (PE: 68.4%) for PTSD. Approximately half (51.3%) of clinicians endorsed using Relapse Prevention (RP) for SUD. The vast majority (97.4%) of clinicians were somewhat or very interested in a new integrative CPT-RP intervention, and 94.7% of clinicians believed patients would be interested in a CPT-RP intervention. In the absence of an available evidence-based integrative treatment using CPT, 84.0% of clinicians reported modifying extant treatment protocols on their own to address PTSD and SUD concurrently., Conclusions: The findings demonstrate mental health clinician support of integrative treatments for PTSD/SUD. The most commonly used trauma-focused intervention was CPT and clinicians expressed strong interest in an integrative intervention that combines CPT and RP. Implications for future treatment development are discussed.

Background and Aims: Identifying modifiable neuropsychological factors associated with more severe CUD could improve CUD treatment. Impairments in processing of non-drug rewards may be one such factor. This study assessed the relationship between reward functioning and cocaine use severity using multi-modal measures of three distinct reward functions: consummatory reward (pleasure or "liking"); motivational reward ("wanting") and reward learning., Methods: Fifty-three adults with at least moderate CUD completed self-report and behavioral measures of consummatory reward, motivational reward and reward learning, and a composite cocaine use severity measure including quantity, frequency and life impacts of cocaine use. We conducted parallel Frequentist and Bayesian multiple regressions with measures of reward functioning as predictors of cocaine use severity., Results: Less self-reported ability to experience pleasure, a hypothesized measure of consummatory reward, significantly predicted greater severity after adjustment for covariates and multiple hypothesis testing, β = 0.39, t(38) = 2.86, p = 0.007. Bayesian analyses confirmed a highly likely association between severity and ability to experience pleasure, and provided moderate evidence for associations with willingness to exert effort and reward learning., Conclusions: Our results suggest that less experience of subjective pleasure is related to greater cocaine use severity. This cross-sectional study cannot establish whether differences in consummatory reward are pre-existing, a result of CUD, or both. However, these results suggest interventions focused on increasing subjective pleasure, such as mindful "savoring", should be investigated for CUD., Competing Interests: Declaration of Competing Interest No conflicts declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial., Methods: The multi-site ADAPT-2 study used a randomized, double blind, sequential parallel comparison design to evaluate treatment with extended-release injectable NTX (380 mg every 3 weeks) combined with once-daily oral extended-release BUP (450 mg/day) vs matching injectable and oral placebo in outpatients with moderate or severe MA use disorder. The study assessed smoking outcomes, based on self-reported timeline followback (TLFB) data, twice/week for 13 weeks., Results: Of the 403 participants in the ADAPT-2 trial, 290 reported being current cigarette smokers (71.9 %). The study found significant differences (p's < 0.0001) for each smoking outcome indicating greater change in the proportion of nonsmoking days, number of cigarettes smoked per week, and consecutive nonsmoking days, all favoring the group receiving NTX-BUP versus placebo., Conclusions: NTX-BUP was associated with significant reductions in self-reported cigarette smoking in the context of concurrent treatment for MA use disorder. These off-target medication effects warrant prospective investigation using biochemically confirmed measures of smoking abstinence. The development of NTX-BUP as a co-addiction treatment strategy has a potential for high public health impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Madhukar Trivedi: Within the past 12 months, Dr. Trivedi has provided consulting services to Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, Daiichi Sankyo Inc, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Otsuka American Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, Relmada Therapeutics, Inc, SAGE Therapeutics, Signant Health, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, and WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, and Merck Sharp & Dohme Corp. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Dr. Thomas Carmody: Dr. Carmody has served as a consultant for Alkermes, Inc. Dr. Stephen Shoptaw: Dr. Shoptaw has received clinical supplies for this research from Alkermes, Inc., (Copyright © 2023. Published by Elsevier Inc.)

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants ( N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices ( Q ₀, essential value [EV], O max , P max , and breakpoint [BP]) were evaluated via Bayesian generalized linear modeling. Positive associations (posterior probabilities ≥ 75%) were found between LPP amplitude and four demand indices ( Q ₀, EV, O max , BP). These results suggest that individuals who attach greater relevance to cocaine cues also exhibit greater valuation of cocaine reward. Implications for incorporating methodology from behavioral science and brain imaging are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cocaine use remains a serious public health problem associated with a marked increase in overdose deaths in the past decade. No medications have yet been proven to be effective for the treatment of cocaine use disorder (CUD). Among the highly promising medications have been glucagon-like peptide 1 receptor agonists (GLP-1RA) that are currently used for the treatment of type 2 diabetes mellitus and weight management. Preclinically, GLP-1RAs have been shown to attenuate cocaine self-administration, however, this has not yet been demonstrated in a human laboratory study. The GLP-1RA extended-release exenatide is given as a once-weekly injection, which may be clinically advantageous for addressing medication nonadherence among individuals with CUD. Here, we assess feasibility and safety by reporting on 3 cases of patients with CUD who received 6 weeks of exenatide 2 mg subcutaneously once-weekly in an open-label fashion, along with standard individual drug counseling. We observed excellent attendance and compliance, along with positive end-of-study satisfaction ratings. The medication was well tolerated and without unexpected or severe adverse events. Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD should utilize a randomized controlled trial design and longer treatment duration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Introduction: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have demonstrated efficacy in reducing both food and nicotine intake. This report describes the design of a double-blind, placebo-controlled, randomised clinical trial that evaluates the effects of the GLP-1RA exenatide as an adjunct to nicotine patches on smoking abstinence and PCWG., Methods and Analysis: The study will be conducted at two university-affiliated research sites in Houston, Texas, the UTHealth Center for Neurobehavioral Research on Addiction and Baylor College of Medicine Michael E. DeBakey VA Medical Centre. The sample will consist of 216 treatment-seeking smokers with pre-diabetes (haemoglobin A1c of 5.7%-6.4%) and/or overweight (body mass index of 25 kg/m 2 or above). Participants will be randomised (1:1) to receive subcutaneous injections of placebo or 2 mg exenatide, once weekly for 14 weeks. All participants will receive transdermal nicotine replacement therapy and brief smoking cessation counselling for 14 weeks. The primary outcomes are 4-week continuous abstinence and changes in body weight at the end of treatment. The secondary outcomes are (1) abstinence and changes in body weight at 12 weeks post end of treatment and (2) changes in neuroaffective responses to cigarette-related and food-related cues as measured by electroencephalogram., Ethics and Dissemination: The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-21-0639) and Baylor College of Medicine Institutional Review Board (H-50543). All participants will sign informed consent. The study results will be disseminated via peer-reviewed publications and conference presentations., Trial Registration Number: NCT05610800., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD ( n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; M age  = 44.90, SD  = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

The increased risk of alcohol use disorder (AUD) in individuals with post-traumatic stress disorder (PTSD) is well-documented. Compared to individuals with PTSD or AUD alone, those with co-existing PTSD and AUD exhibit greater symptom severity, poorer quality of life, and poorer treatment outcomes. Although the treatment of comorbid AUD is vital for the effective management of PTSD, there is a lack of evidence on how to best treat comorbid PTSD and AUD, and currently, there are no FDA-approved treatments for the PTSD-AUD comorbidity. The objective of this manuscript is to review the evidence of a promising target for treating the AUD-PTSD comorbidity. First, we summarize the epidemiological evidence and review the completed clinical studies that have tested pharmacotherapeutic approaches for co-existing AUD and PTSD. Next, we summarize the shared pathological factors between AUD and PTSD. We conclude by providing a rationale for selectively inhibiting aldehyde dehydrogenase-2 as a potential target to treat comorbid AUD in persons with PTSD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety 'in the moment', broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a covariate. The sample was comprised of 53 adults (48.1% women; 75.9% African American; 74.1% with past-month PTSD) with substance dependence per DSM-IV and at least four symptoms of PTSD per DSM-5. Higher baseline nonjudgmental acceptance predicted greater safety and control in response to substance cues; no effects were found for craving. These experimental laboratory results elucidate the potential clinical utility of mindfulness-based interventions in bolstering recovery from addiction among adults with SUD/PTS by fostering safety and control in response to substance cues., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Opioid misuse and opioid-related death are a growing public health concern. One population of interest is recent trauma and/or surgery patients, who are at increased risk of developing an opioid use disorder (OUD). Although a variety of assessments have been developed to screen for risk of opioid misuse, each has limitations and prediction needs improvement. One promising measure is drug demand, a behavioral economic measure assessing drug consumption at different price points. In the current proposal, we assessed the utility of a brief assessment of opioid demand. Demand and various pain-related self-report measures among trauma-surgery patients ( N = 103) were assessed at 4 weeks post-discharge. Opioid demand was significantly associated with self-report measures of pain and amount of morphine milligram equivalents (MME) received during the hospital stay. The current result support the utility of the opioid demand as an adjunctive and complementary measure to assess risk of opioid misuse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: Prescription opioids are an effective pain treatment strategy but can lead to long-term opioid misuse. Identifying at risk patients during hospitalization can inform the development of prevention interventions post-discharge. Using the Opioid Risk Tool (ORT) as a screening measure, this study predicted factors associated with pain and opioid use at 2 weeks post-discharge in trauma patients., Design: A quality improvement prospective study design was used., Setting: Participant recruitment took place at an inpatient Level 1 trauma center in Houston, Texas., Participants: Participants (n = 103) were patients admitted to the adult trauma service. Patients completed the ORT in the hospital and a survey at 2 weeks post-discharge., Main Outcome Measure: The survey assessed pain intensity and interference, injury-related stress, medication use, and need for additional pain treatment. Wilcoxon-Mann-Whitney U test, the Spearman rank-order correlation, and chisquare test of independence tested the ORT as a predictor of follow-up outcomes. Post hoc analyses relied on logistic and quantile regression., Results: The ORT identified 15.5 percent of patients at high risk for opioid-related aberrant behavior. Survey results indicated high percentages of patients reporting moderate to severe pain (79.6 percent), pain interference (77.9 percent), taking pain pills (59.6 percent), experiencing stress (76.9 percent), and needing pain treatment (52.4 percent). The ORT predicted injury-related stress with the high-risk category having higher stress levels than low risk (Z = 2.518, p = 0.012)., Conclusion: Risk of opioid misuse assessed in hospitalized trauma patients was associated with injury-related stress reported post-discharge. This highlights the importance of including stress assessments in follow-up appointments.

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose., Methods: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the "winner" in this DTL trial., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder., Methods: We recorded electroencephalogram on 52 trauma-exposed participants (M age = 51.3; SD = 7.0; 15.4 % women) diagnosed with cocaine use disorder while they viewed pleasant (i.e., erotic, romantic, sweet foods), unpleasant (i.e., mutilations, violence, accidents), neutral, and cocaine-related images. Reactivity was measured with the late positive potential (LPP), an indicator of motivational relevance. It was hypothesized that individuals with greater PTSD avoidance and negative alterations in cognition and mood (NACM) symptoms, as determined by the PTSD Checklist for DSM-5 (PCL-5), would have higher LPPs to cocaine-related images, indicating greater cue reactivity., Results: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues., Conclusions: These results highlight the potential clinical utility of the LPP in assessing drug cue reactivity in trauma-exposed adults with substance use disorder., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A hypothetical cocaine purchasing task (CocPT) was used to assess changes in cocaine demand in the context of contingency management (CM) treatment for cocaine use disorder (CUD). Participants (N = 89) were treatment-seeking individuals with CUD receiving 4 weeks of abstinence-based, high-magnitude CM. Treatment response (vs. non-response) was operationally defined as the submission of 6 consecutive cocaine-negative urine samples across two weeks. The CPT was assessed at baseline, week 2, and week 5. Demand data were well described by the exponentiated demand model, and baseline demand indices (Q 0 , P max , breakpoint, essential value) were significantly associated with self-report measures of cocaine use. The probability of being a zero-responder reporting zero cocaine consumption at all prices significantly increased over the course of treatment, and was greater among treatment responders vs. non-responders. Among non-zero demand data, decreases in O max , P max , breakpoint, and essential value were observed over the course of CM treatment, favoring responders. To our knowledge, this is the first study to assess change in cocaine demand in the context of CM treatment targeting cocaine abstinence. Our results support the utility of cocaine demand as a measure for both identifying individuals with greater treatment need and tracking relapse risk over the course of treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome., Methods: Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes., Results: Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively., Conclusions: Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies., Implications: Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chronic cocaine users show impairments in cognitive processes associated with dopamine (DA) circuitry. Medications aimed at bolstering cognitive functions via DA modulation might enhance treatment outcome., Methods: The trial used a double-blind, double-dummy, parallel-group design with four treatment arms comparing placebo (PLC) to levodopa/carbidopa 800 mg/200 mg alone (LR0), levodopa plus extended release (XR) ropinirole 2 mg (LR2) or XR ropinirole 4 mg (LR4). Adults (n = 110) with cocaine use disorder attended thrice weekly clinic visits for 10 weeks. Potential cognitive mediators assessed at week 5 consisted of measures of decision-making (Iowa Gambling Task, Risky Decision-Making Task), attention/impulsivity (Immediate Memory Task), motivation (Progressive Ratio task), and cognitive control (Cocaine Stoop task). The primary outcome measure was the treatment effectiveness score (TES) calculated as the number of cocaine-negative urines collected from weeks 6-10., Results: Bayesian mediation examined indirect and total effects of the relationships between each active treatment (compared to PLC) and TES. Total (direct) effects were supported for LR0 and LR2, but not for LR4. Indirect effects were tested for each mediator. Notably, 22.3 % and 35.4 % of the total effects of LR0 and LR2 on TES were mediated by changes in attention/impulsivity., Conclusions: The hypothesized mediation effect was strongest for levodopa plus 2 mg ropinirole, indicating that this DA medication combination predicted change (improvement) in attention/impulsivity, which in turn predicted change (reduction) in cocaine use. This finding provides modest support for cognitive enhancement as a target for medications to treat cocaine use disorder., (Copyright © 2021. Published by Elsevier B.V.)

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD)., Aim: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not., Methods: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders., Results: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only., Conclusions: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement.

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature., (© 2020 Society for the Study of Addiction.)

Substance use disorders (SUD) commonly co-occur with posttraumatic stress disorder (PTSD) symptoms, and the comorbidity is prevalent and difficult-to-treat. Few studies have objectively analyzed language use in psychotherapy as a predictor of treatment outcomes. We conducted a secondary analysis of patient language use during cognitive-behavioral therapy (CBT) in a randomized clinical trial, comparing a novel, integrated CBT for PTSD/SUD with standard CBT for SUD. Participants included 37 treatment-seeking, predominantly African-American adults with SUD and at least four symptoms of PTSD. We analyzed transcripts of a single, matched session across both treatment conditions, using the Linguistic Inquiry and Word Count (LIWC) program. The program measures language use across multiple categories. Compared to standard CBT for SUD, patients in the novel, integrated CBT for PTSD/SUD used more negative emotion words, partially consistent with our hypothesis, but less positive emotion words. Further, exploratory analyses indicated an association between usage of cognitive processing words and clinician-observed reduction in PTSD symptoms, regardless of treatment condition. Our results suggest that language use during therapy may provide a window into mechanisms active in therapy.

Background: Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment., Objective: We assessed 18 cytokines, cocaine use, cognition, and depression in individuals with Cocaine Use Disorder. Our general hypothesis was that higher pro-inflammatory cytokines would relate to more cocaine use, poorer cognition, and more depression, while higher anti-inflammatory cytokines would relate to less cocaine use, better cognition, and less depression., Methods: Data were collected from 85 individuals (76.5% male, 80% African American) aged 18-65. The ASI, Shipley-2, and BDI-II assessed frequency and duration of cocaine use, cognition, and depression. Cytokines were tested using Bio-Plex Pro™ assays. Elastic net regression identified which cytokines related to each measure, controlling for confounds., Results: Lower IL-29 (B = -0.08, bootstrapped 95%CI = [-0.24,0.07]), scD163 (B = -0.11, bootstrapped 95%CI = [-0.27,0.04]), Eotaxin-1 CCL11 (B = -0.11, bootstrapped 95%CI = [-0.30,0.08]), and higher APRIL/TNFSF13 (B = 0.11, bootstrapped 95%CI = [-0.08,0.30]) related to more frequent cocaine use. Lower IL-29 (B = -0.24, bootstrapped 95% CI = [-2.26,1.79]) and IL-20 (B = -1.62, bootstrapped 95%CI = [-3.53,0.29]) related to longer duration of cocaine use. Higher Eotaxin-2 CCL24 (B = 2.79, bootstrapped 95%CI = [-0.59,6.17]) and TWEAK (B = 2.83, bootstrapped 95%CI = [-0.80,6.45]) related to better cognition. Finally, higher IL-20 (B = -1.83, bootstrapped 95%CI = [-3.70,0.04]) and Osteocalcin (B = -1.56, bootstrapped 95%CI = [-3.81,0.70]) related to lower depressive symptoms. However, none of these relationships survived bootstrapped analyses., Conclusion: Pro- and anti-inflammatory cytokines may relate to cocaine use, cognition, and depression, but inconsistent with our hypotheses, higher pro-inflammatory cytokines related to better functioning in several domains. Additionally, cytokines were selected at low frequencies and demonstrated weak relationships with outcomes. These preliminary findings suggest complex relationships between inflammation and cocaine use.

Exchange sex places individuals with cocaine use disorder (CUD) at particularly high risk for deleterious safety and health outcomes. A substance use treatment provider who is aware of a patient's exchange sex behavior is better able to provide appropriate screening, care, and/or referral to risk reduction services. However, little is known about exchange sex, especially purchasing, among treatment-seeking adults with CUD., The current study examined the prevalence and correlates of sex selling and sex purchasing among treatment-seeking men and women with CUD ( n  = 109; ClinicalTrials.gov #NCT02896712). Separate binary logistic regressions via backward elimination were used to identify best fitting models for sex selling and sex purchasing., Over 41% of participants endorsed exchange sex within the last 30 days; 20.2% reported selling sex and 30.3% reported purchasing sex. Sex selling and sex purchasing rates differed by gender and race. Number of sexual partners (OR = 5.83, 95% CI = 2.07-16.43), concern about contracting HIV/AIDS (OR = 2.01, 95% CI = 1.31-3.44), cumulative interpersonal trauma exposure (OR = 1.82, 95% CI = 1.20-2.77), years using cocaine (OR = 1.11, 95% CI = 1.03-1.20), drug-related problem days (OR = 1.07, 95% CI = 1.00-1.14), and sexual preference (OR = 9.50, 95% CI = .69-130.35) were retained in the final model estimating sex selling (Nagelkerke R 2 = .56). In the final sex purchasing model (Nagelkerke R 2 = .46), gender (OR = 36.17, 95% CI = 2.96-441.75), number of sexual partners (OR = 6.28, 95% CI = 2.69-14.66), number of convictions (OR = 1.13, 95% CI = 1.02-1.25), and drug-related problem days (OR = 0.96, 95% CI = .92-1.01) were retained., Predictive models in this study identified distinct sets of variables related to sex selling and purchasing. Findings may be used to improve identification of exchange sex in the substance use treatment setting and referral to targeted interventions to reduce associated risk.

Background: Tobacco product use is a significant public health concern, particularly with the increasing use of electronic nicotine delivery systems (electronic cigarettes [e-cigarettes]). Dental care providers are well positioned to screen and provide guidance regarding tobacco use, but these services are generally underused., Methods: In preparation for a quality improvement project, patients at a large academic dental school clinic were anonymously surveyed regarding past and current use of combustible cigarettes and e-cigarettes, attitudes about quitting, and health beliefs regarding these products., Results: Among 166 surveyed patients, past month use of combustible cigarettes, e-cigarettes, and both combustible cigarettes and e-cigarettes (dual use) was reported by 14.5%, 2.4%, and 5.4% of patients, respectively. Daily combustible cigarette, e-cigarette, and dual use was reported by 12.7%, 1.2%, and 1.8% of patients, respectively. Most current tobacco users expressed thoughts or plans about changing their tobacco use and concerns regarding continued use of these products on their oral health. More than one-half of the current tobacco users expressed interest in receiving additional support to help them quit., Conclusions: Dental care providers see a sizable number of patients who use combustible cigarettes and e-cigarettes, many of whom are concerned about the potential harms of these products on their health and express interest in tobacco-use cessation support., Practical Implications: It is critical that dental care professionals engage in efforts to assess combustible cigarette and e-cigarette use and provide guidance regarding these products to their patients., (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

The co-occurrence of posttraumatic stress disorder (PTSD) and substance use disorders (SUD) is highly prevalent and difficult-to-treat. Mindfulness, defined as nonjudgmental attention to and awareness of present-moment experiences, represents a targetable mechanism with potential to predict and improve treatment outcomes for PTSD/SUD populations. We hypothesized that greater self-reported mindfulness at baseline (pre-treatment) would predict (a) lower end-of-treatment PTSD severity and (b) greater longest sustained abstinence during a 12-week cognitive-behavioral treatment program. Participants included 53 inner-city adults meeting at least four current symptoms of DSM-5 PTSD and current (DSM-IV) substance dependence (51% women; 75.5% African American; Mage = 45.42, SD = 9.99). Hierarchical regression analysis results indicated that higher levels of baseline mindfulness predicted lower end-of-treatment PTSD severity but not longest sustained abstinence from the primary substance of choice. Post hoc exploration of end-of-treatment PTSD symptom clusters indicated that higher baseline mindfulness predicted lower intrusion, negative alterations in cognitions and mood, and arousal and reactivity symptoms but not avoidance symptoms. Clinical and research implications are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: Current evidence and literature reviews provide a strong justification for examining the orexin receptor (OXR) system as a therapeutic target in substance use disorders, including cocaine and other psychostimulants., Objectives: In this preliminary, proof-of-concept examination of orexin modulation in humans with cocaine use disorder, we measured changes in domains tied to relapse: stress, sleep, cue reactivity, and inhibitory control. Additionally, mood symptoms (anxiety, depression), medication compliance, and side effects were assessed., Methods: Twenty non-treatment seeking subjects with cocaine use disorder (CUD) received either the OX 1 R / OX 2 R antagonist suvorexant PO or placebo at 10 PM daily for two weeks (10 mg week 1, 20 mg week 2). Using psychometrics, smart-watch actigraphy, a cold-pressor stress challenge, and eye-tracking technology, the following domains were examined: sleep, stress/anxiety, cue-reactivity (attentional bias, craving), and inhibitory control. Psychometric data were collected every M/W/F (7 time points). Laboratory data were collected weekly (3 time points)., Results: Bayesian and frequentist generalized linear models were employed in parallel to examine the effects of suvorexant compared to placebo, with a Bayesian posterior probability threshold >80% as evidence of a signal for suvorexant. Notable results favoring suvorexant over placebo included fewer total anti-saccade errors, improved sleep actigraphy (sleep/awake periods), pre/post cold-pressor change in heart rate and salivary cortisol (all posterior probabilities >94%), and craving (posterior probability >87%)., Conclusions: Initial but restricted evidence is provided supporting the orexin system as a modulator of relapse-related processes in cocaine use disorder. Baseline differences in the main outcome variables were not experimentally controlled and differences in craving were observed at baseline. This, in combination with a limited sample size, constrain the nature of the project. The results may serve to inform more comprehensive future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To evaluate a hospital-initiated intervention to reduce tobacco smoke exposure in infants in the neonatal intensive care unit., Study Design: A randomized, controlled trial compared motivational interviewing plus financial incentives with conventional care on infant urine cotinine at 1 and 4 months' follow-up. Mothers of infants in the neonatal intensive care unit (N = 360) who reported a smoker living in the home were enrolled. Motivational interviewing sessions were delivered in both the hospital and the home. Financial incentives followed session attendance and negative infant cotinine tests postdischarge., Results: The intervention effect on infant cotinine was not significant, except among mothers who reported high baseline readiness/ability to protect their infant (P ≤ .01) and mothers who completed the study within 6 months postdischarge (per protocol; P ≤ .05). Fewer mothers in the motivational interviewing plus financial incentives condition were smoking postdischarge (P ≤ .01). More mothers in the motivational interviewing plus financial incentives group reported a total home and car smoking ban at follow-up (P ≤ .05)., Conclusions: Motivational interviewing combined with financial incentives reduced infant tobacco smoke exposure in a subset of women who were ready/able to protect their infant. The intervention also resulted in less maternal smoking postpartum. More robust interventions that include maternal and partner/household smoking cessation are likely needed to reduce the costly effects of tobacco smoke exposure on children and their families., Trial Registration: ClinicalTrials.gov: NCT01726062., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The neutrophil to lymphocyte ratio (NLR) is a non-specific, easy-to-obtain marker of inflammation associated with morbidity and mortality in systemic, psychiatric, and age-related inflammatory conditions. Given the growing trend of substance use disorder (SUD) in older adults, and the relationship between inflammation and SUD elevated NLR may serve as a useful inflammatory biomarker of the combined burden of aging and SUD. The present study focused on cocaine use disorder (CUD) to examine if cocaine adds further inflammatory burden among older adults, by comparing NLR values between older adults with CUD and a non-cocaine using, aged-matched, nationally representative sample., Methods: The dataset included 107 (86% male) participants (aged 50-65 years) with cocaine use disorder. NLR was derived from complete blood count tests by dividing the absolute value of peripheral neutrophil concentration by lymphocyte concentration. For comparison, we extracted data from age-matched adults without CUD using the National Health and Nutrition Examination Survey. Individuals with immunocompromising conditions were excluded (e.g., rheumatoid arthritis and sexually transmitted infections such as HIV). A doubly-robust inverse probability-weighted regression adjustment (IPWRA) propensity score method was used to estimate group differences on NLR while controlling for potential confounding variables (age, gender, race, income, nicotine, marijuana and alcohol use)., Results: The IPWRA model revealed that the CUD sample had significantly elevated NLR in comparison to non-cocaine users, with a moderate effect size (β weight = 0.67)., Conclusion: Although non-specific, NLR represents a readily obtainable inflammatory marker for SUD research. CUD may add further inflammatory burden to aging cocaine users.

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants ( N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [ Q ₀], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q ₀ (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q ₀ revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Individuals with cannabis use disorders (CUD) show inhibitory control deficits and differential attention toward marijuana (MJ) stimuli. The robustness and utility of these measures in the CUD literature are somewhat equivocal. The present study was designed to increase measurement sensitivity by capitalizing on (a) individually calibrated stimulus selection based on cue reactivity patterns and (2) eye-tracking based measurement. CUD (n = 42) and non-CUD controls (n = 11) served as subjects. Subjects were first exposed to MJ and neutral pictures while measuring physiological and subjective responses on a trial by trial basis. A single reactivity index was created for each stimulus (L2 vector norm). Subject-unique high-reactivity MJ and low-reactivity neutral stimuli were then used in an eye-tracking task (pro-/antisaccade). The stimulus calibration procedure produced large reactivity differences between high/MJ and low/neutral stimuli (p < .001, effect size >7). CUD subjects made more overall antisaccade errors than controls (inhibitory control, p < .02, effect size >1), and CUD subjects (but not controls) made more errors on MJ trials versus neutral trials (attentional bias, p < .002, effect size >1). Within CUD subjects, L2 vector norm scores were associated with antisaccade errors (p < .04), and antisaccade errors were correlated with the Perceived Stress Scale (p < .03) and marginally with CUD severity (p < .07). Because of precise understanding of the neural circuitry governing antisaccades (a marker in several neuro/psychiatric disorders), eye movement-based measures combined with individually determined stimuli may provide an efficient and robust marker in CUD research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Post-traumatic stress disorder (PTSD) symptoms are highly prevalent among individuals with substance use disorders (SUD), presenting a difficult-to-treat, complex comorbidity. Prognostic factors for treatment outcomes may characterize heterogeneity of the treated population and/or implicate mechanisms of action that are salient for improving treatments. High frequency heart rate variability (HF-HRV) is a suggested biomarker for emotion regulation-the ability to generate appropriate emotional responses via the influence of the parasympathetic nervous system on the heart. This initial study investigated the utility of baseline resting HF-HRV for predicting PTSD symptoms and substance use outcomes following treatment of 37 SUD participants with comorbid PTSD symptoms. Participants completed either standard cognitive- behavioral therapy (CBT) for SUD or a novel treatment of integrated post-traumatic stress and substance use that combined CBT for SUD with cognitive processing therapy for PTSD. Analyses demonstrated that higher HF-HRV predicted greater reduction in PTSD symptoms following both types of treatment. This suggests prognostic value of HF-HRV as a predictor of PTSD treatment outcomes; those with poorer autonomic emotional regulation may not respond as well to psychotherapy in general. This hypothesis-generating analysis identifies a putative biomarker that might have utility in treatment prediction., (© 2019 Society for Psychophysiological Research.)

Background: Converging lines of evidence from diffusion tensor imaging (DTI) studies reveal significant alterations in white matter (WM) microstructure in the prefrontal cortex of chronic stimulant users compared to controls, suggesting compromised axonal microstructure and/or myelin., Methods: A meta-analysis of DTI-based WM integrity was conducted for white matter regions across the corpus callosum and association fibers. Articles were sourced and selected using PRISMA guidelines for systematic review and meta-analysis. Inclusion and exclusion criteria were determined by the authors in order to best capture WM integrity among individuals with primary stimulant use in comparison to healthy control subjects., Results: Eleven studies that focused on region-of-interest (ROI)-based analysis of WM integrity were extracted from an initial pool of 113 independent studies. Analysis across ROIs indicated significantly lower fractional anisotropy (FA) values in stimulant use groups compared to controls with a small to moderate overall effect (Hedges' g = -0.37, 95% CI [-0.54, -0.20]). Eigenvalues were also analyzed, revealing a significant effect for radial diffusivity (RD; Hedges' g = 0.24, 95% CI [0.01, 0.47]) but not axial diffusivity (AD; Hedges' g = 0.05, 95% CI [-0.20, 0.29]) or mean diffusivity (MD; Hedges' g = 0.20, 95% CI [-0.01, 0.41]). Subgroup analyses based on specific ROIs, primary substance use, poly-substance use, and imaging technology were also explored., Conclusion: Results of the present study suggest a consistent effect of compromised WM integrity for individuals with stimulant use disorders. Furthermore, no significant differences were found between cocaine and methamphetamine-based groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are complex psychiatric conditions that commonly co-occur. No preferred, evidence-based treatments for PTSD/SUD comorbidity are presently available. Promising integrated treatments have combined prolonged exposure therapy with cognitive-behavioral relapse prevention therapy for SUD. We describe a case study that showcases a novel, integrated cognitive-behavioral treatment approach for PTSD/SUD, entitled Treatment of Integrated Posttraumatic Stress and Substance Use (TIPSS). The TIPSS program integrates cognitive processing therapy with cognitive-behavioral therapy for SUD for the treatment of co-occurring PTSD/SUD. The present case report, based upon a woman with PTSD comorbid with both cocaine and alcohol dependence, demonstrates that TIPSS has the potential to effectively reduce PTSD symptoms as well as substance use., Competing Interests: The authors declare that there are no conflicts of interest.

Tobacco use disorder (TUD), in particular cigarette smoking, contributes significantly to the macro- and micro-vascular complications of type 2 diabetes mellitus (DM). Persons with DM who regularly use tobacco products are twice as likely to experience mortality and negative health outcomes. Despite these risks, TUD remains prevalent in persons with DM. The objective of this integrative review is to summarize the relationship between TUD and DM based on epidemiological and preclinical biological evidence. We conclude with a review of the literature on the glucagon-like peptide-1 (GLP-1) as a potential treatment target for addressing comorbid TUD in smokers with DM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, resulting in changes consistent with an allostatic load model of neurocognitive impairment. The present study measured potential markers of allostatic load in individuals with comorbid cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white matter (WM), telomere length, and impulsivity/attentional bias were obtained. WM (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by the telomere to single copy gene (T/S) ratio. Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and FA were associated with years of cocaine use (R2 = 0.56 and 0.51, both p < .005) but not years of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, exploratory regression using an elastic-net model determined that more years of cocaine use, older age, larger HDDM drift rate differences and shorter telomere length were all predictive of WM as measured by RD (model R2 = 0.79). Collectively, the results provide modest support linking CUD/AUD to putative markers of allostatic load., Competing Interests: The authors have declared that no competing interests exist.

Background: Depressive symptoms may contribute to cocaine use. However, tests of the relationship between depression and severity of cocaine use have produced mixed results, possibly due to heterogeneity in individual symptoms of depression. Our goal was to establish which symptoms of depression are most strongly related to frequency of cocaine use (one aspect of severity) in a large sample of current cocaine users. We utilized generalized additive modeling to provide data-driven exploration of the relationships between depressive symptoms and cocaine use, including examination of non-linearity. We hypothesized that symptoms related to anhedonia would demonstrate the strongest relationship to cocaine use., Method: 772 individuals screened for cocaine use disorder treatment studies. To measure depressive symptoms, we used the items of the Beck Depression Inventory, 2nd Edition. Cocaine use frequency was measured as proportion of self-reported days of cocaine use over the last 30 days using the Addiction Severity Index., Results: Models identified 18 significant predictors of past-30-day cocaine use. The strongest predictors were Crying, Pessimism, Changes in Appetite, Indecisiveness, and Loss of Interest. Noteworthy effect sizes were found for specific response options on Suicidal Thoughts, Worthlessness, Agitation, Concentration Difficulty, Tiredness, and Self Dislike items., Conclusions: The strongest predictors did not conform to previously hypothesized "subtypes" of depression. Non-linear relationships between items and use were typical, suggesting BDI-II items may not be monotonically increasing ordinal measures with respect to predicting cocaine use. Qualitative analysis of strongly predictive response options suggested emotional volatility and disregard for the future as important predictors of use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Substance use disorders and posttraumatic stress symptoms are commonly comorbid. Previous studies have established that those with substance use disorders or posttraumatic stress disorder (PTSD) have lower high frequency-heart rate variability (HF-HRV) compared to controls, suggesting that low HF-HRV may be a biomarker of a common physiological mechanism underlying both disorders. We evaluated HF-HRV as a potential biomarker of a common underlying process by testing whether lower HF-HRV related to greater severity of substance use and PTSD symptoms in individuals with both substance use disorders and at least four symptoms of PTSD. Methods: HF-HRV was measured in 49 adults with substance use disorders and at least four symptoms of PTSD. We performed a series of regressions controlling for age to test whether low HF-HRV was associated with greater substance use disorder and PTSD symptom severity. Substance use disorder symptoms were measured by the Addiction Severity Index and PTSD symptoms were measured by the Clinician-Administered PTSD Scale and the PTSD Checklist. Results: After controlling for age, low resting HF-HRV was significantly associated with drug and alcohol symptom severity but not PTSD symptom severity. Conclusions: HF-HRV may be more sensitive to the severity of drug and alcohol use rather than PTSD. Findings may suggest that in PTSD populations, HF-HRV may primarily index comorbid substance use disorder symptoms. HF-HRV could serve as an objective measure of substance use severity and should be further investigated as a predictor of outcomes in treatment for substance use disorders.