N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial.

BACKGROUND: Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis. METHOD: In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. CONCLUSION: Results will inform smoking cessation treatment among dual users of tobacco and cannabis. CLINICALTRIALS: gov Identifier: NCT04627922.

Perceived discrimination enhances the association between distress and impact related to the murder of George Floyd and unhealthy alcohol use in a survey sample of U.S. Veterans who report drinking.

Introduction: On May 25, 2020, George Floyd was murdered by a Minneapolis police officer leading to increased social justice and antiracism movements (SJARM) across the United States. Vicarious exposure to racism and perceived discrimination are salient sources of distress which may lead to increased alcohol use as means of coping. The primary aim of the current study was to examine how perceived discrimination and the subjective impact and personal distress related to the SJARM following the George Floyd murder interact and relate to unhealthy alcohol use among U.S. Veterans. Methods: 286 Veterans were assessed for unhealthy alcohol use (AUDIT-10), perceived discrimination (EDS), and subjective impact and personal distress related to the SJARM. Two moderation analyses were performed to examine whether subjective impact and personal distress moderated relations between perceived discrimination and alcohol use. In-depth follow-up analyses were conducted to examine differences and relationships among variables. Results: In two different moderation models, perceived discrimination moderated the association between both subjective impact (p <.001) and personal distress (p <.001) felt by the SJARM and unhealthy alcohol use. In planned exploratory analyses, Veterans who reported perceived discrimination reported higher levels of unhealthy alcohol use (M = 14.71, SD = 9.39) than those who did not t(2 8 4) = 5.61, p <.001. In post-hoc analyses, racial/ethnic minorities were significantly more likely to report perceived racial discrimination (p <.001) while non-Hispanic Whites were more likely to report perceived discrimination based on education or income level (p <.01). Conclusions: In the context of a socially unjust event amidst a global pandemic, perceived discrimination contributes to unhealthy alcohol use and subjective impact and personal distress associated with the SJARM following the murder of George Floyd. Results highlight the importance of addressing discrimination experiences in Veterans who seek alcohol treatment, particularly as rates of unhealthy alcohol use are on the rise.

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Impact of Alcohol Use, Traumatic Stress, and Cigarette Smoking on Cognitive Functioning in Veterans With Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder.

INTRODUCTION: Alcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD. MATERIALS AND METHODS: U.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition. RESULTS: Smoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers. CONCLUSIONS: Overall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

The Impact of Exercise and Virtual Reality Executive Function Training on Cognition Among Heavy Drinking Veterans With Traumatic Brain Injury: A Pilot Feasibility Study.

Executive function (EF) underlies self-control deficits in alcohol use disorder (AUD) and traumatic brain injury (TBI). Cognitive training is a promising adjunctive treatment targeting TBI- and AUD- related cognitive dysfunction. However, major limitations related to compliance and generalizability in the field of cognitive training exist. Physical activity is associated with enhanced cognitive performance across several executive functions and may enhance the benefits of cognitive training. Virtual reality provides multisensory embodied experiences which are likely to engage brain networks more efficiently than standard cognitive training systems, ultimately resulting in greater near- and far-transfer effects. This pilot study aimed to obtain feasibility data and a preliminary assessment of an enriched virtual reality (VR) EF training (EFT) intervention combined with exercise (NCT03786276). Using an 8-week randomized adaptive design study, 30 AUD treatment seeking U.S. Veterans completed nine sessions of exercise-only (n = 15) or gameplay control (n = 15) over 3 weeks, followed by a week-4 repeat assessment in Phase 1. Twenty-three participants completed and moved onto Phase II, where they completed up to nine sessions of VR-EFT plus exercise and completed a week-8 end-of-study assessment. Primary outcomes included feasibility to retain participants, usability, and satisfaction of using VR-EFT. Secondary and exploratory outcomes included within group assessment of change in cognitive function, alcohol use, alcohol craving, and post-concussive symptoms among the three treatment conditions.VR-EFT was feasible with moderate usability and high acceptability ratings.The most common VR-related adverse effect was motion sickness (n = 2/16, 12.5%). The VR-EFT condition was associated with significant improvement in inhibition-switching and visual scanning (both p < 0.05) during Phase II. Exercise-only was associated with significant improvements in cognitive inhibition, cognitive flexibility, reductions in alcohol craving, and number of standard alcohol drinks per week (all p ≤ 0.05). The gaming-control condition was associated with improvement in cognitive flexibility and visuospatial immediate recall (both p < 0.05) during Phase 1. Recruitment and retention of U.S. veterans with AUD and TBI into an exercise plus VR-EFT intervention is feasible, but technological barriers may impact usability. VR-EFT was associated with improvement in executive function domains that were targeted in as little as 3-week and nine sessions of VR-EFT exposure. Results are promising and indicate the need for a larger controlled investigation to assess the efficacy of VR-EFT to enhance treatment outcomes among AUD treatment-seeking U.S. veterans with co-occurring AUD and TBI. Clinical Trial Registration: www.ClinicalTrials.gov, Identifier: NCT03786276.

Factors associated with smoking in low-income persons with and without chronic illness.

INTRODUCTION: Tobacco disparities persist among low-income smokers who seek care from safety-net clinics. Many of these patients suffer from chronic illnesses (CILs) that are associated with and exacerbated by smoking. The objective of the current study was to examine the differences between safety-net patients with and without CILs in terms of nicotine dependence and related factors (such as depression, anxiety) and self-efficacy regarding ability to abstain from smoking. METHODS: Sixty-four low-income smokers who thought about or intended to quit smoking were recruited from the San Francisco Health Network (SFHN) and assessed for CILs, nicotine dependence, depression, anxiety, and smoking abstinence self-efficacy. Four one-way analyses of variance were used to examine the difference between those with and without CIL on the latter four variables. RESULTS: The CIL group had significantly higher anxiety (CIL: 8.0 ± 5.35; non-CIL: 4.44 ± 3.48; p=0.02) and tended to have higher nicotine dependence (CIL: 5.40 ± 2.58; non-CIL: 3.88 ± 2.28; p=0.04). In the CIL group, nicotine dependence was positively correlated with anxiety [r(62)=0.39; p<0.01] and negatively correlated with smoking abstinence self-efficacy [r(62)= -0.38; p<0.01]. Both depression (Spearman's rho=0.39; p<0.01) and anxiety (Spearman's rho=0.29; p<0.05) were associated with total number of CIL categories. CONCLUSIONS: Safety-net patients who smoke and suffer from CILs may be suffering from higher levels of anxiety and have less confidence in their ability to quit smoking. Incorporating mood management and developing interventions that increase a sense of self-efficacy for refraining from smoking may be necessary to help low-income smokers quit smoking.

Working memory and alcohol demand relationships differ according to PTSD symptom severity among veterans with AUD.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid with complex and often unclear associations. Working memory deficits may represent a shared mechanism implicated in emotion regulation and control over impulsive alcohol use. Here we test whether PTSD symptoms and working memory correlated with performance on a behavioral economic assessment of alcohol demand. 113 veterans (mean age 51 years; 89% male) completed an Alcohol Purchase Task (APT) and were assessed for PTSD, alcohol use, and working memory. We examined the interaction of PTSD symptoms and working memory on four indices of alcohol demand measured from the APT; specifically, we used separate models to test whether associations between working memory and intensity (consumption at $0), Omax (maximum expenditure), Pmax (price at maximum expenditure), and elasticity (price sensitivity), differed as a function of PTSD symptoms. In a model controlling for hazardous drinking, average drinking levels, age, sex, marital status, occupation, and education, we observed a significant interaction between PTSD symptoms and working memory on elasticity, whereby greater working memory capacity was associated with greater elasticity for veterans with lower PTSD symptoms. Follow-up analyses regarding specific PTSD symptom domains indicated that this effect was strongest for avoidance symptoms. Taken together, working memory abilities correlated with subjective valuations of alcohol in a laboratory setting for veterans with less severe PTSD symptoms. This work highlights the conditions under which working memory may be a potential target for interventions geared toward reducing alcohol use in veterans with co-occurring PTSD and AUD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

An initiative to increase opioid overdose education and naloxone distribution for homeless veterans residing in contracted housing facilities.

BACKGROUND: Up to 35% of veterans with opioid use disorder (OUD) are homeless, and veterans with OUD are nearly 29 times higher risk for homelessness; however, few are prescribed naloxone, an evidence-based intervention to reverse life-threatening opioid overdose. LOCAL PROBLEM: Many housing facilities for homeless veterans contracted with the San Francisco Veterans Affairs Health Care System are located in neighborhoods with high rates of opioid overdose. No systematic interventions have been implemented to provide opioid overdose education and naloxone kits to veterans and staff at these facilities. This quality improvement (QI) initiative aimed to increase provision of opioid overdose education and naloxone for veterans and staff at contracted housing facilities. METHODS: This was a prospective single-arm cohort QI intervention. All contracted veteran housing programs were included. Descriptive statistics evaluated results. INTERVENTIONS: A total of 18 contracted veteran housing programs were contacted from July 2019 through January 2020 to schedule training. RESULTS: Of those, 13 programs responded to outreach and 10 visits were completed at 8 housing facilities. Training was provided by pharmacist and nurse practitioner trainers to 26 staff members and 59 veterans. Naloxone was prescribed to 37 veterans. CONCLUSIONS: A pharmacist-led and nurse practitioner-led initiative was effective in increasing veteran and staff access to opioid overdose education and naloxone at >44% contracted veteran housing facilities. Challenges included lack of response from housing programs, low veteran turn out, and inability to provide naloxone to veterans not enrolled/ineligible for health care. Future initiatives should examine strategies to standardize access in homeless veterans' programs.

Substance-Specific and Shared Gray Matter Signatures in Alcohol, Opioid, and Polysubstance Use Disorder.

Substance use disorders (SUD) have been shown to be associated with gray matter (GM) loss, particularly in the frontal cortex. However, unclear is to what degree these regional GM alterations are substance-specific or shared across different substances, and if these regional GM alterations are independent of each other or the result of system-level processes at the intrinsic connectivity network level. The T1 weighted MRI data of 65 treated patients with alcohol use disorder (AUD), 27 patients with opioid use disorder (OUD) on maintenance therapy, 21 treated patients with stimulant use disorder comorbid with alcohol use disorder (polysubstance use disorder patients, PSU), and 21 healthy controls were examined via data-driven vertex-wise and voxel-wise GM analyses. Then, structural covariance analyses and open-access fMRI database analyses were used to map the cortical thinning patterns found in the three SUD groups onto intrinsic functional systems. Among AUD and OUD, we identified both common cortical thinning in right anterior brain regions as well as SUD-specific regional GM alterations that were not present in the PSU group. Furthermore, AUD patients had not only the most extended regional thinning but also significantly smaller subcortical structures and cerebellum relative to controls, OUD and PSU individuals. The system-level analyses revealed that AUD and OUD showed cortical thinning in several functional systems. In the AUD group the default mode network was clearly most affected, followed by the salience and executive control networks, whereas the salience and somatomotor network were highlighted as critical for understanding OUD. Structural brain alterations in groups with different SUDs are largely unique in their spatial extent and functional network correlates.

A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms.

BACKGROUND: Topiramate is an effective treatment for alcohol use disorder (AUD) and has also been used in the care of mild traumatic brain injury (mTBI). This pilot study aimed to obtain a preliminary assessment of topiramate's efficacy in reducing alcohol use and post-concussive symptoms, and its potential negative impact on cognitive function in 32 Veterans with co-occurring AUD and mTBI. METHODS: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot study of flexible-dose topiramate or placebo. Primary outcome was reduction of drinking days per week within the topiramate arm. Secondary outcomes included between group comparisons of alcohol use and craving, post-concussive symptoms, and cognitive function. RESULTS: Drinking days per week significantly decreased within both the topiramate and placebo arm. There were no significant treatment-by-week interactions on alcohol use/craving, or post-concussive symptoms in intent-to-treat analyses. In per-protocol analyses, topiramate significantly reduced number of drinks per week compared with placebo. Topiramate transiently impaired verbal fluency and working memory. Processing speed, cognitive inhibition, and mental flexibility significantly improved between weeks 1 and 12, regardless of treatment arm. CONCLUSIONS: Significant improvement occurred in both the topiramate and placebo groups over 12 weeks of treatment in alcohol use and post-concussive symptoms. Among treatment completers there was greater reduction of alcohol use in the topiramate arm. Topiramate was also associated with negative but transient effects on cognitive function. Results suggest both a possible benefit for topiramate treatment in reducing alcohol use and some potential for negative cognitive effects in Veterans with AUD and mTBI.

An electronic intervention to improve safety for pain patients co-prescribed chronic opioids and benzodiazepines.

BACKGROUND: Co-prescribing opioids and benzodiazepines increases overdose risk. A paucity of literature exists evaluating strategies to improve safety of co-prescribing. This study evaluated an electronic intervention to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines at 3 and 6 months. METHODS: A prospective cohort study was conducted from December 2015 through May 2016 at San Francisco Veterans Affairs Health Care System. A clinical dashboard identified 145 eligible patients prescribed chronic opioids and benzodiazepines. Individualized taper and safety recommendations were communicated to prescribers via electronic medical record progress note and encrypted e-mail at baseline. Primary outcome was number of patients co-prescribed chronic opioids and benzodiazepines. Secondary outcomes included daily dose of opioids and benzodiazepines and number prescribed ≥100 mg morphine equivalent daily dose. Safety outcomes included number with opioid overdose education and naloxone distribution, annual urine drug screening, annual prescription drug monitoring program review, and signed opioid informed consent. Linear mixed models and generalized estimating equations were used to examine within-group change in outcomes between baseline and 3 and 6 months. RESULTS: Among the 145 patients, mean (standard deviation) age was 62 (11) years and 91.7% (133/145) were male. Number co-prescribed significantly decreased from 145/145 (100%) at baseline to 93/139 (67%) at 6-month follow-up (odds ratio [OR] = 0.53, 95% confidence interval [CI]: 0.34-0.81, P = .003). Mean opioid and benzodiazepine doses significantly decreased from 84.61 to 65.63 mg (95% CI: 8.32-27.86, P < .001) and from 16.10 to 13.45 mg (95% CI: 1.6-3.9, P < .001), respectively, from baseline to 6-month follow-up. Patients prescribed ≥100 mg morphine equivalent daily dose significantly decreased from 39/145 (26.8%) at baseline to 26/139 (18.7%) at end of study (OR = 0.59, 95% CI: 0.44-0.78, P < .001), and patients with opioid overdose education and naloxone distribution significantly increased from 3/145 (2.1%) at baseline to 46/139 (33.1%; OR = 23.4, 95% CI: 7.61-71.99, P < .001) by the end of study. Number of patients with annual urine drug screening tended to increase from 123/145 (84.8%) at baseline to 132/145 (91.4%) by the end of study (OR = 1.89, 95% CI: 0.95-3.76, P = .07), and there were no significant changes across time in numbers of patients with annual prescription drug monitoring program review or signed opioid informed consent. CONCLUSIONS: Electronic interventions may provide an effective strategy to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines.

Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol.

Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP-). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP- and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP-, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA.

Neurocognition and inhibitory control in polysubstance use disorders: Comparison with alcohol use disorders and changes with abstinence.

INTRODUCTION: Intact neurocognition and early cognitive recovery during abstinence are important for substance use treatment outcome. Yet, little is known about them in the largest group of treatment seekers today, individuals with polysubstance use disorders (PSU). This study primarily contrasted PSU and individuals with an alcohol use disorder (AUD) on neurocognitive and inhibitory control measures and, secondarily, measured changes during abstinence in PSU. METHOD: At one month of abstinence from all substances except tobacco, 36 PSU and 69 AUD completed neurocognitive assessments of executive function, general intelligence, auditory-verbal learning/memory, visuospatial learning/memory/skills, processing speed, working memory, fine motor skills, and cognitive efficiency. The groups were also assessed on inhibitory control measures of self-reported impulsivity, risk-taking, and decision-making. Seventeen PSU repeated the assessments after approximately four months of abstinence. All cross-sectional and longitudinal analyses included smoking status as a possible confound. RESULTS: At baseline, PSU performed significantly worse than AUD on auditory-verbal memory and on an inhibitory control measure of impulsivity. Polysubstance users showed trends to worse performance than AUD on general intelligence, auditory-verbal learning, and a decision-making task. Between one and four months of abstinence, PSU showed significant improvements on several neurocognitive and inhibitory control measures. CONCLUSIONS: Polysubstance users exhibit distinct differences in neurocognition and inhibitory control compared to AUD. Between one and four months of abstinence, neurocognition and inhibitory control improve in PSU. This neurocognitive recovery in some domains of abstinent PSU is influenced by smoking status. These results underscore the clinical value of select methods to augment neurocognitive recovery in PSU through appropriate interventions.

Relations Between Cognitive Functioning and Alcohol Use, Craving, and Post-Traumatic Stress: An Examination Among Trauma-Exposed Military Veterans With Alcohol Use Disorder.

Cognitive dysfunction is commonly observed among individuals with alcohol use disorder (AUD) and trauma exposure and is, in turn, associated with worse clinical outcomes. Accordingly, disruptions in cognitive functioning may be conceptualized as a trans-disease phenomenon representing a potential high-yield target for intervention. Less is known though about how different cognitive functions covary with alcohol use, craving, and post-traumatic stress symptom severity among trauma-exposed individuals with AUD. Sixty-eight male and female trauma-exposed military veterans with AUD, entering treatment trials to reduce alcohol use, completed measures assessing alcohol use and craving, post-traumatic stress symptom severity, and cognitive functioning. In multivariate models, after controlling for post-traumatic stress symptom severity, poorer learning and memory was associated with higher alcohol consumption and higher risk taking/impulsivity was associated with stronger preoccupations with alcohol and compulsions to drink. Alcohol consumption and craving, but not performance on cognitive tests, were positively associated with post-traumatic stress symptom severity. Findings suggest that interventions to strengthen cognitive functioning might be used as a preparatory step to augment treatments for AUD. Clinicians are encouraged to consider a standard assessment of cognitive functioning, in addition to post-traumatic stress symptom severity, in treatment planning and delivery for this vulnerable and high-risk population.

Alcohol use disorder with and without stimulant use: brain morphometry and its associations with cigarette smoking, cognition, and inhibitory control.

OBJECTIVE: Little is known about the effects of polysubstance use and cigarette smoking on brain morphometry. This study examined neocortical brain morphometric differences between abstinent polysubstance dependent and alcohol-only dependent treatment seekers (ALC) as well as light drinking controls (CON), the associations of cigarette smoking in these polysubstance users (PSU), and morphometric relationships to cognition and inhibitory control. METHODS: All participants completed extensive neuropsychological assessments and 4 Tesla brain magnetic resonance imaging. PSU and ALC were abstinent for one month at the time of study. Parcellated morphological data (volume, surface area, thickness) were obtained with FreeSurfer methodology for the following bilateral components: dorso-prefrontal cortex (DPFC), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and insula. Regional group differences were examined and structural data correlated with domains of cognition and inhibitory control. RESULTS: PSU had significantly smaller left OFC volume and surface area and trends to smaller right DPFC volume and surface area compared to CON; PSU did not differ significantly from ALC on these measures. PSU, however, had significantly thinner right ACC than ALC. Smoking PSU had significantly larger right OFC surface area than non-smoking PSU. No significant relationships between morphometry and quantity/frequency of substance use, alcohol use, or age of onset of heavy drinking were observed. PSU exhibited distinct relationships between brain structure and processing speed, cognitive efficiency, working memory and inhibitory control that were not observed in ALC or CON. CONCLUSION: Polysubstance users have unique morphometric abnormalities and structure-function relationships when compared to individuals dependent only on alcohol and light drinking controls. Chronic cigarette smoking is associated with structural brain irregularities in polysubstance users. Further elucidation of these distinctive characteristics could help inform the development of targeted and thus potentially more effective treatments in this large but understudied population.

Effects of cigarette smoking history on neurocognitive recovery over 8 months of abstinence in alcohol-dependent individuals.

BACKGROUND: This study compared the rate and extent of recovery on measures of learning and memory, processing speed, and working memory in treatment-seeking alcohol-dependent individuals (ALC) who were never smokers (nvsALC), former smokers (fsALC), and active smokers (asALC) over the first 8 months of sustained abstinence from alcohol. Assessments after 1 week, 1 month, and 8 months of abstinence in ALC enabled a comparison of the rates of neurocognitive changes from 1 week to 1 month versus 1 to 8 months of abstinence. METHODS: ALC and never-smoking controls were administered standardized measures of auditory-verbal and visuospatial learning and memory, processing speed, and working memory. Controls completed a baseline assessment and a follow-up approximately 9 months later. RESULTS: Over 8 months of abstinence, asALC showed poorer recovery than nvsALC on visuospatial learning, and both fsALC and asALC recovered less than nvsALC on processing speed measures. The corresponding recovery rates for the ALC group, as a whole, were greater from 1 week to 1 month than from 1 to 8 months of abstinence; these findings were largely driven by improvements in nvsALC. The recovery levels for fsALC on most measures were similar to those in asALC. Additionally, over 8 months, asALC showed significantly less improvement with increasing age than nvsALC on measures of processing speed and learning and memory. At 8 months of abstinence, asALC were inferior to controls and nvsALC on multiple measures, fsALC performed worse than nvsALC on several tests, but nvsALC were not different from controls on any measure. CONCLUSIONS: Overall, ALC showed rapid improvement on measures of visuospatial learning and processing speed during the first month of abstinence from alcohol. Results also provide robust evidence that smoking status influenced the rate and level of neurocognitive recovery over 8 months of abstinence in this ALC cohort.

Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol.

Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned.

Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial.

BACKGROUND: The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders. METHODS: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity. RESULTS: Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment. CONCLUSIONS: These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated.