Search

Alcohol abuse is a leading risk factor for the public health burden worldwide. Approved pharmacotherapies have demonstrated limited effectiveness over the last few decades in treating alcohol use disorders (AUD). New therapeutic approaches are therefore urgently needed. Historical and recent clinical trials using psychedelics in conjunction with psychotherapy demonstrated encouraging results in reducing heavy drinking in AUD patients, with psilocybin being the most promising candidate. While psychedelics are known to induce changes in gene expression and neuroplasticity, we still lack crucial information about how this specifically counteracts the alterations that occur in neuronal circuits throughout the course of addiction. This review synthesizes well-established knowledge from addiction research about pathophysiological mechanisms related to the metabotropic glutamate receptor 2 (mGlu2), with findings and theories on how mGlu2 connects to the major signaling pathways induced by psychedelics via serotonin 2A receptors (2AR). We provide literature evidence that mGlu2 and 2AR are able to regulate each other's downstream signaling pathways, either through monovalent crosstalk or through the formation of a 2AR-mGlu2 heteromer, and highlight epigenetic mechanisms by which 2ARs can modulate mGlu2 expression. Lastly, we discuss how these pathways might be targeted therapeutically to restore mGlu2 function in AUD patients, thereby reducing the propensity to relapse. [ABSTRACT FROM AUTHOR]

Background: Changing addictive behavior is a complex process with high demands on motivation. The Transtheoretical Model of Behavior Change provides a theoretical framework for explaining and predicting behavioral change, although its predictive value for addiction is somewhat inconsistent. Objective: The aim of the present study is to extend the Transtheoretical Model of Behavior Change by investigating not only treatment motivation but also the predictive value of the type of drinking-related treatment goal. Additional predictors, such as substance-related and sociodemographic variables, are also included in analyses seeking to predict return to drinking during relapse prevention treatment for alcohol use disorder. Methods: In this observational study, 99 inpatients from a treatment center for alcohol use disorder were recruited. Treatment motivation was assessed in accordance with the Transtheoretical Model of Behavior Change, drinking-related treatment goal through a self-report questionnaire, and substance-related and sociodemographic variables via the clinic information system. Associations between the potential predictors and covariates were explored using stepwise logistic regression. Results: During treatment, 42.6% of participants had at least one relapse. Scoring higher on the action dimension at admission (OR = 0.81, p =.04) and being employed (OR = 0.37, p =.02) were significant predictors of abstinence during treatment. Conclusions: This study confirms that treatment motivation contributes to the prediction of treatment outcome, even when controlling for other variables. In future research, the underlying mechanisms of treatment motivation should be further explored. [ABSTRACT FROM AUTHOR]

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government. [ABSTRACT FROM AUTHOR]

Background: Cognitive‐behavioral therapy (CBT) has long‐standing evidence for efficacy in the treatment of alcohol use, yet implementation in clinical practice has been challenging. Delivery of CBT through technology‐based platforms, such as web‐based programs and mobile applications, has the potential to provide widespread access to this evidence‐based intervention. While there have been reviews indicating the efficacy of technology‐based delivery of CBT for various psychiatric conditions, none have focused on efficacy for alcohol use. The current meta‐analysis was conducted to fill this research gap. Methods: Descriptive data were used to characterize the nature of the literature on technology‐delivered, CBT‐based interventions for alcohol use ("CBT Tech"). Inverse‐variance‐weighted effect sizes were calculated, and random effects, effect sizes were pooled in 4 subgroups. Results: Fifteen published trials conducted primarily with at‐risk or heavy drinkers were identified. Of these studies, 60% explicitly targeted alcohol use moderation. The content of CBT Tech programs varied, ranging from 4 to 62 sessions/exercises, with many programs combining elements of motivational interviewing (47%). With respect to efficacy, CBT Tech as a stand‐alone treatment in contrast to a minimal treatment control showed a positive and statistically significant, albeit small effect (g = 0.20: 95% CI = 0.22, 0.38, kes = 5). When CBT Tech was compared to treatment as usual (TAU), effects were nonsignificant. However, when CBT Tech was tested as an addition to TAU, in contrast to TAU only, the effect size was positive, significant (g = 0.30: 95% CI = 0.10, 0.50, kes = 7), and stable over 12‐month follow‐up. Only 2 studies compared CBT Tech to in‐person CBT, and this pooled effect size did not suggest superior efficacy. Conclusions: These results show a benefit for technology‐delivered, CBT‐based interventions as a stand‐alone therapy for heavy drinking or as an addition to usual care in specialty substance use settings. This meta‐analysis of technology‐delivered, CBT‐based interventions (CBT Tech) targeting alcohol use across 15 independent randomized controlled trials indicated CBT Tech interventions were efficacious at reducing alcohol use. The largest pooled effects (g = 0.3) were produced from studies that evaluated CBT Tech interventions as an add‐on to treatment as usual. Although the overall magnitude is small, this pooled effect size is similar to those found in meta‐analyses of computer‐based interventions for other substances. [ABSTRACT FROM AUTHOR]

The article presents clinical practice guidelines on assessment and management of substance abuse disorder in children and adolescents. Topics discussed include psychoeducation of patient and family with special emphasis on harm minimization, significance of Benzodiazepines (BZD) in pharmacotherapy during acute stage alcohol detoxification.

Aims: This 12-week, open-label, primary care study (NCT02195817) evaluated the efficacy and safety of nalmefene, taken as needed, to reduce alcohol consumption in adults with a diagnosis of alcohol dependence and drinking at least at high drinking risk levels (DRL, > 60 g/day for men, > 40 g/day for women).Methods: Following the Screening Visit, patients recorded their daily alcohol consumption for 2 weeks. Patients were then categorised by their self-reported drinking levels; those who maintained at least a high DRL in the 2-week period were included in Cohort-A, and those who reduced their alcohol consumption below high DRL were included in Cohort-B. Cohort-A received simple psychosocial interventions and were supplied with nalmefene 18 mg to be taken on days when they perceived a risk of drinking alcohol. Patients in Cohort-B received a simple psychosocial intervention and were treated per normal practice.Results: Of the 378 enrolled patients, 330 were included in Cohort-A and 48 in Cohort-B. For patients in Cohort-A, the mean change from screening to Week-12 in the number of heavy drinking days/month was -13.1 days/month (95% CI -14.4 to -11.9, p < 0.0001). Overall, 55% of patients reduced their DRL by ≥2 risk levels and 44% of patients reduced to a low DRL. The most common adverse events were nausea (18.3%) and dizziness (17.7%). Patients in Cohort-B maintained their lower level alcohol consumption at the 12-week follow-up.Conclusions: Patients with alcohol dependence treated in primary care with nalmefene, taken as needed, in conjunction with simple psychosocial support, significantly reduced their alcohol consumption. Treatment was well tolerated. [ABSTRACT FROM AUTHOR]

Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI -28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000-0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and tolerability of baclofen vs. placebo for long‐term treatment of alcohol use disorder. Method: Systematic review and meta‐analysis following methods of the Cochrane Collaboration Handbook (PROSPERO registration: CRD42017073663). Primary outcome was the random‐effects summary estimate of all standardized mean differences (SMDs), as calculated from the primary outcomes of each study. Results: Fourteen double‐blind RCTs (1522 patients) were included. Heterogeneity was substantial for most analyses (I2 about 75%). Baclofen showed a small, but not statistically significant superiority over placebo: SMD = 0.22 ([95% CI: −0.03; 0.47], P = 0.09). This result was supported by a leave‐one‐out‐analysis, and Orwin's fail‐safe N, by predefined secondary analyses (on abstinence rates and amount of drinking), and by a post hoc‐analysis of high‐dose studies (>80 mg/day). An analysis of low risk of bias studies (SMD = 0.10 [−0.20; 0.41], P = 0.51, I2 = 43.3%) found no effect. Exclusion of four studies focusing on patients with comorbidity yielded a small positive effect. Drop‐out rates were similar. Conclusion: Our results question baclofen's utility in the long‐term treatment of alcohol use disorder at both normal and high doses. While the confidence intervals indicate that marginally harmful or moderately beneficial effects of baclofen remain a possibility, the most likely effect size is slightly above placebo effects. [ABSTRACT FROM AUTHOR]

Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has raised some interest for the treatment of alcohol use disorder (AUD), occasionally at dose up to 300 mg/d. We conducted the first full-profile pharmacokinetic study on baclofen in AUD subjects, up to the oral daily dose of 300 mg. Sixty subjects treated for AUD with marketed baclofen were enrolled in a prospective phase-1 study. Participants were divided into four dose groups (1: <60 mg/d; 2: 60–120 mg/d; 3: >120 mg/d-180 mg/d; and 4: >180 mg/d), and they underwent a full-profile pharmacokinetic analysis of baclofen, using a nonlinear mixed effects modeling. The influence of different clinical and biological covariates was assessed in an upward modeling. Fifty-seven participants completed the study (522 observed concentrations collected). Racemic baclofen showed a linear pharmacokinetic profile, corresponding to a one-compartment model, with no influencing clinical or biological factor. The pharmacokinetic parameters of baclofen were (bootstrap 95% confidence intervals): absorption constant (Ka) 1.64 1/h (1.34–2), clearance (Cl/F) 11.6 L/h (10.8–12.3) and volume of distribution (Vd/F) 72.8 L (66.5–80.4) leading to a half-life of 4.4 h. The interindividual variability (IIV) was 44% (19–65), 21% (16–27), and 22% (11–36) for Ka, Cl/F, and Vd/F, respectively. The residual variability was 24% (21–26). No serious adverse event was reported. Registration : EudraCT #2013-003412-46 [ABSTRACT FROM AUTHOR]

Objectives: Alcohol misuse and depression are commonly co-occurring conditions. To date, no review has examined the most efficacious treatment model for psychosocial treatment of co-occurring alcohol misuse and depression. This systematic review determined the: (i) methodological quality of publications examining psychosocial treatment of co-occurring alcohol misuse and depression using a sequential, parallel or integrated treatment model; and (ii) effectiveness of each dual treatment model compared to single treatment for those with co-occurring alcohol misuse and depression. Methods: PubMed, Medline and PsycInfo databases were searched for studies which were included if they involved treatment for alcohol misuse and depression and could be classified into one of the three treatment models. Included studies were assessed using the Cochrane's Effective Practice and Organisation of Care risk of bias criteria. Relevant study characteristics and outcomes were extracted and are presented in a narrative review format. Results: Seven studies met inclusion criteria. None were categorised as low risk on the risk of bias criteria. No studies examined a sequential model of treatment, three examined a parallel model and four examined an integrated model of dual-focussed treatment. The studies examining the parallel model and two out of four studies examining the effectiveness of an integrated model demonstrated greater improvement for alcohol or depression outcomes compared to control conditions. Conclusion: Evidence for the psychosocial treatment of co-occurring alcohol misuse and depression is limited to a handful of studies. The evidence has several methodological limitations, which impact the interpretation of the findings. Therefore, while international guidelines recommend integrated dual-focussed treatment for co-occurring conditions, there is little evidence supporting the superiority of this treatment format for co-occurring alcohol misuse and depression. High-quality research demonstrating improvements in patient outcomes is required to ensure recommendations for clinical practice are based on strong empirical evidence. [ABSTRACT FROM AUTHOR]

Introduction: This secondary data analysis examined whether and how the dopamine receptor D4 gene (DRD4) influenced naltrexone treatment responsiveness in a randomized clinical trial. We leveraged intensive experience sampling methods to test the hypothesis that craving recorded at drinking and non-drinking moments would mediate naltrexone effects on the likelihood of heavy drinking, but only among carriers of the DRD4 long (DRD4-L) allele.Methods: Participants (Mage=29.8years, SD=12.1) were non-treatment seeking heavy drinkers (n=104, 54.8% female, 61.5% alcohol dependent) randomized to 3weeks of daily naltrexone (50mg) or placebo. During these 3weeks, participants used handheld electronic devices to complete real-time reports of alcohol use and craving multiple times per day in their natural environments. This approach afforded intensive repeated assessment of focal variables and provided in-the-moment data to test whether craving when not drinking or early in drinking episodes explained naltrexone effects on drinking.Results: Moderated-mediation multilevel structural equation models showed that craving during non-drinking moments mediated the treatment effect of naltrexone on heavy drinking but only among carriers of the DRD4-L allele. The same pattern of associations was not shown when evaluating craving while participants were consuming alcoholic beverages.Conclusions: Findings provide the first in vivo evidence that, among carriers of the DRD4-L allele, naltrexone blunts craving in real-world settings, and this effect in turn reduces the likelihood of heavy drinking. This work highlights the utility of EMA methods for elucidating how treatments work and further demonstrates the importance of genetic factors for understanding individual differences in pharmacotherapy responsiveness. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This narrative exploration of alcohol treatment research focuses on key contentions and advances in alcohol treatment during the critical 1970s and 1980s. Methods: Papers and books which signal some of the major debates and advances in alcohol treatment research were selected from the 1970s and 1980s. The selection process was based on significant debate during this period, and included those that influenced the field in general and this author in particular. Results: This was a period where challenges to traditional models and concepts, and the perceived universal need for long‐term treatment, were accompanied by contention but also advances in research and treatment approaches. The debates and advances resonate today. These include the recognition that: intensive and long‐term treatment is not always required; for dependent drinkers, relapse is a common treatment outcome meriting specific treatment approaches to prevent and reduce this risk; controlled drinking is a treatment option, especially for younger and less dependent drinkers; and an important contributor to enduring change is access to, and realization of, improvements in the quality of life. Conclusions: Pioneering research and publications in the 1970s and 1980s, sometimes conducted and produced in contentious contexts, influenced significantly conceptualizations of alcohol‐related problems, and laid the foundations for treatment hypotheses and research, improving access to a broader range of evidence‐based treatment. These underpinning works influenced the development of stepped‐up care from brief to intensive interventions, relapse prevention and treatment options not limited to abstinence, and they identified the need to include a stronger focus on quality of life. [ABSTRACT FROM AUTHOR]

Provision of alternative non-drug reinforcement is among the most effective methods for treating substance use disorders. However, when alternative reinforcers become unavailable during treatment interruptions or upon cessation of treatment, relapse often occurs. Relapse following the loss of alternative reinforcement is known as resurgence. One factor that could reduce resurgence is longer duration of treatment with alternative reinforcement, but the available data are mixed. Further, the effects of length of treatment have previously only been examined with food seeking. The present experiments directly examined if duration of treatment impacted the magnitude of resurgence of cocaine or alcohol seeking in rats. First, rats were trained to self-administer cocaine (Experiment 1) or alcohol (Experiment 2) by performing a target behavior. Second, target behavior was extinguished and performing an alternative behavior produced an alternative non-drug (i.e., food) reinforcer. Finally, resurgence was assessed following removal of alternative reinforcement after either 5 or 20 sessions of treatment. Treatment duration did not differentially affect resurgence of cocaine seeking in Experiment 1 or Alcohol seeking in Experiment 2. These results suggest that extended treatment with alternative non-drug reinforcement may not decrease propensity to relapse. Further, these results may have implications for treatment of substance use disorders and for theories of resurgence. [ABSTRACT FROM AUTHOR]

It has been identified that chronic ethanol exposure damages the nervous system, particularly neurons. There is scientific evidence suggesting that neuronal loss caused by chronic ethanol exposure has an association with neuron apoptosis and intracellular calcium oscillation is one of the primary inducers of apoptosis. Therefore, the present study aimed to investigate the inductive effects of intracellular calcium oscillation on apoptosis in SK‑N‑SH human neuroblastoma cells and the protective effects of the N‑methyl‑D‑aspartic acid receptor (NMDAR) antagonist, memantine, on SK‑N‑SH cell apoptosis caused by chronic ethanol exposure. SK‑N‑SH cells were treated with 100 mM ethanol and memantine (4 μM) for 2 days. Protein expression of NR1 was downregulated by RNA interference (RNAi). Apoptosis was detected by Annexin V/propidium iodide (PI) double‑staining and flow cytometry and cell viability was detected using an MTS kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration and the levels of NR1 and caspase‑3 were detected using western blotting. NR1 mRNA levels were also detected using qPCR. It was found that chronic ethanol exposure reduced neuronal cell viability and caused apoptosis of SK‑N‑SH cells, and the extent of damage in SK‑N‑SH cells was associated with ethanol exposure concentration and time. In addition, chronic ethanol exposure increased the concentration of intracellular calcium in SK‑N‑SH cells by inducing the expression of NMDAR, resulting in apoptosis, and memantine treatment reduced ethanol‑induced cell apoptosis. The results of the present study indicate that the application of memantine may provide a novel strategy for the treatment of alcoholic dementia. [ABSTRACT FROM AUTHOR]

The A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (Oprm1) has been implicated in mediating the rewarding effects of alcohol. Clinical and preclinical studies suggest that the G allele may confer a genetic vulnerability to alcohol dependence, though it remains unknown whether these effects are sex-specific. We used male and female mice homozygous for the “humanized” 118AA or 118GG alleles to determine whether the A118G SNP potentiates ethanol consumption in a sex-specific manner in both the two-bottle choice and drinking-in-the-dark (DID) paradigms. Mice were also assessed for differences in naltrexone sensitivity, ethanol reward assessed via conditioned place preference (CPP), and sensitivity to the sedative/ataxic effects of ethanol using the rota-rod and loss of righting reflex (LORR) assays. We found that male and female 118GG mice drank significantly more ethanol than 118AA littermates using a continuous access, two-bottle choice paradigm. In the limited-access DID drinking model, (i) female (but not male) 118GG mice consumed more ethanol than 118AA mice and (ii) naltrexone pretreatment was equally efficacious at attenuating ethanol intake in both 118AA and 118GG female mice while having no effect in males. Male and female 118GG and female 118AA mice developed a robust conditioned place preference (CPP) for ethanol. Female 118GG mice displayed less sensitivity to the sedative/ataxic effects of ethanol compared to female 118AA mice on both the rota-rod and the LORR assays while male mice did not differ in their responses on either assay. Our findings suggest that increased ethanol consumption in male 118GG mice may be due to increased ethanol reward, while increased drinking in female 118GG mice might be due to decreased sensitivity to the sedative/ataxic effects of ethanol. Collectively, these data might be used to help identify sex-specific pharmacotherapies to combat alcohol use disorders. [ABSTRACT FROM AUTHOR]

Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to modulate ethanol behaviors in adult humans and in animal models; however, the role of these receptors in adolescent ethanol behaviors has not been explored. Throughout adolescence, nAChR expression undergoes large-scale developmental changes which may alter behavioral responses to ethanol. Here we examined the effect of varenicline, a nAChR partial agonist, on ethanol consumption, ataxia, sedation, and metabolism in adolescent male and female C57BL/6J mice. The effect of varenicline on ethanol consumption was tested through the Drinking-in-the-Dark (DID) paradigm that models binge-like ethanol consumption. To ensure that results were specific for ethanol, we also tested the effect of varenicline on saccharin consumption. Additionally, varenicline was administered 30 min prior to an acute injection of ethanol before being tested for ataxia on the balance beam, sedation using the loss of righting reflex, or ethanol metabolism. Varenicline dose dependently decreased ethanol consumption, but also influenced saccharin intake. Varenicline showed no significant effect on ethanol metabolism, ataxia, or sedation. Unlike its effects in adult animals, varenicline is able to reduce ethanol consumption without increasing the ataxic and sedative effects of ethanol. This work suggests that the neurobiological mechanisms of ethanol behaviors may change across the lifespan and highlights the need for more research on the role of nAChRs in ethanol behaviors throughout development. [ABSTRACT FROM AUTHOR]

This research contributes a first-hand account of the experiences of youth's substantial unpaid familial caregiving in the context of long-term illness, disability or problems related to alcohol and/or other drugs. A qualitative focus group methodology explored the benefits and challenges of youth's caregiving via a sample of 15 youth caregivers (or young carers) from both the Greater Toronto area and the Niagara Region of Southern Ontario. The findings reveal evidence for a unique "young carer penalty," a term coined by this research to build upon the gendered "care penalty" experienced by adult women (especially mothers) when performing care work. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD. [ABSTRACT FROM AUTHOR]

Research on the clinical applications of psychedelic-assisted psychotherapy has demonstrated promising early results for treatment of alcohol dependence. Detailed description of the content and methods of psychedelic-assisted psychotherapy, as it is conducted in clinical settings, is scarce. Methods: An open-label pilot (proof-of-concept) study of psilocybin-assisted treatment of alcohol dependence (NCT01534494) was conducted to generate data for a phase 2 RCT (NCT02061293) of a similar treatment in a larger population. The present paper presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions. Results: Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin. Discussion: The data illuminate change processes in patients' own words during clinical sessions, shedding light on potential therapeutic mechanisms of change and how participants express effects of psilocybin. This study is unique in analyzing actual clinical sessions, as opposed to interviews of patients conducted separately from treatment. [ABSTRACT FROM AUTHOR]

Background: despite a 450% increase in UK alcohol-related liver disease mortality over the past 30 years, little evidence-based guidance exists regarding preventing recidivism post-liver transplant for alcohol-related liver disease. Method: a systematic literature review was conducted to identify demographic variables predictive of alcohol relapse and effective psychosocial interventions for alcohol-related liver disease patients post-liver transplant. Results: variables most significantly predictive of alcohol relapse post-transplant were—less than 12 months pre-liver transplant abstinence; patients with children; poor pre-liver transplant psychosomatic evaluation; non-compliance with post-liver transplant treatment plan; and patients with active insurance policies. Structured management was the most effective psychosocial intervention in preventing alcohol relapse. Conclusion: findings should be interpreted cautiously, due to limited and poor-quality evidence. Rigorously designed further research of the psychosocial interventions targeting predictive demographic variables is recommended. [ABSTRACT FROM AUTHOR]

Alcohol consumption is a major risk factor for the acquisition of HIV/AIDS and is associated with greater disease burden and mortality among those who become HIV-infected. Of the extant pharmacological treatments for alcohol use disorders, naltrexone is recognized as one of the most efficacious, producing robust reductions in alcohol craving and use. Given that treatment with oral naltrexone has been limited by problems with adherence, which are particularly prevalent among individuals with multiple chronic, co-occurring conditions, long-acting formulations may be a promising approach for HIV-infected substance users. However, little is known about the barriers to initiation of extended-release naltrexone (XR-NTX) treatment among alcohol users living with HIV. In this report we present and discuss the content analysis of open-ended survey questions, as well as lessons learned, with regards to barriers to initiation and maintenance of XR-NTX treatment collected as part of an RCT evaluating a cognitive behavioral text messaging intervention for HIV-infected adults with alcohol use disorders. Barriers to initiation and maintenance of XR-NTX pharmacotherapy among HIV+ individuals with alcohol use disorders seem to fall in one of two categories: [1] barriers that are amenable to change, which include distance and transportation issues, fear of injections, and belief that alcohol use does not warrant pharmacotherapy, and [2] barriers that are not amenable to change, such as the potential interaction of XR-NTX with another medication regimen. [ABSTRACT FROM AUTHOR]

Objective: The aim was to test if people with different alcohol use problem severity benefitted differentially from brief alcohol interventions delivered in-person versus through computer-generated feedback letters.Methods: Nine hundred sixty-one 18-64year old general hospital inpatients with at-risk alcohol use (mean age=40.9years [standard deviation=14.1], 75% men) were randomized to a) in-person counseling, b) computer-generated individualized feedback letters, or c) assessment only. Both interventions were delivered on the ward and 1 and 3 months later. Outcome was the change in the self-reported alcohol use per day at 6-, 12-, 18-, and 24-month follow-up. The Alcohol Use Disorder Identification Test (AUDIT) score was tested as a moderator of the effect of in-person counseling and computer-generated feedback letters, with higher AUDIT scores indicating more severe alcohol problems.Results: Compared to assessment only, computer-generated feedback letters more strongly reduced alcohol use over 24 months among persons with AUDIT scores of about 8 and lower (ps <0.05). In-person counseling tended to be superior over assessment only among persons scoring high on the AUDIT, but differences were not statistically significant. Six-, 12-, and 18-month differences between in-person counseling and computer-generated feedback letters were significant (ps<0.05) for persons with AUDIT scores below 7.1-7.7. The differences between both interventions attenuated at 24-month follow-up.Conclusions: Computer-based intervention delivery may be superior over in-person delivery for people with low levels of alcohol use problem severity, whereas those with more severe alcohol problems may require more intensive care. [ABSTRACT FROM AUTHOR]

Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking.Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence.Design, Setting, and Participants: This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017.Interventions: Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking.Main Outcomes and Measures: Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16.Results: Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, -0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, -0.69; 95% CI, -1.63 to 0.25; P = .15; Cohen d = -0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = -0.60; 95% CI, -1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07).Conclusions and Relevance: Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks.Trial Registration: clinicaltrials.gov Identifier: NCT01553136. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a major global health concern. Many treatment modalities have been used in past to help decrease the use of alcohol. Recently, a growing interest has been seen in neuromodulation as a novel treatment means to reduce alcohol addiction behavior. Studies on the effect of Transcranial Direct Current Stimulation (tDCS), especially over dorsolateral prefrontal cortex (DLPFC) have been conducted that have shown to reduce craving and relapse behavior in AUD. Adverse effects associated with tDCS are found to be minor and are temporary in nature. However, the results are preliminary as only few studies are done. More research on AUD done using tDCS will help improve our knowledge and understanding on the various factors involved in AUD besides helping to prevent the cycle of craving, relapse and abstinent. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the results of a cognitive-behavioral group therapy applied in an outpatient unit to treat drug addiction. The sample consisted of 130 males with an alcohol dependence disorder. Around 56% of the sample completed treatment - they were given therapeutic discharge. From those, 75.3% never resumed treatment, increasing to 77.7% when patients completed the check-up period after discharge. Follow-up from therapeutic discharge varies from 2 to 18 years; 58% of patients with personality disorders completed treatment with therapeutic discharge. Cognitive-behavioral treatment, whose essential components are detailed in the present study, is effective for the group treatment of patients with alcohol dependence and a comorbid personality disorder. [ABSTRACT FROM AUTHOR]

Objective: Commitment to change is an innovative potential mediator and mechanism of behavior change (MOBC) that has not been examined in adolescents with substance use disorders (SUD). The Adolescent Substance Abuse Goal Commitment (ASAGC) questionnaire is a reliable and valid 2-scale measure developed to assess the adolescent's commitment to either abstinence or harm reduction (HR) that includes consumption reduction as a stated treatment goal. The objective of this study was to examine the ASAGC's ability to predict alcohol use treatment outcome.Method: During sessions three and nine of a 10-week treatment program, therapists completed the ASAGC for 170 adolescents 13-18years of age with alcohol use disorder (AUD). Drinking behaviors were assessed during and after a continued-care phase until 12-month from study onset.Results: Analysis of Variance results indicated that adolescents who reported no alcohol use had significantly higher scores on the commitment to abstinence scale than adolescents who reported alcohol use. None of the ANOVA models were significant for commitment to HR. When treatment outcome was examined, commitment to abstinence consistently predicted number of drinking days, number of heavy drinking days, and the maximum number of drinks post-treatment. In contrast, commitment to HR did not predict any of the drinking outcomes. These results suggest that the more adolescents were committed to abstinence during treatment, the less they used and abused alcohol after treatment completion.Conclusions: In addition to the ASAGC's ability to differentiate between commitment to abstinence and commitment to HR, study findings demonstrate that goal commitment consistently predicts AUD treatment outcome. [ABSTRACT FROM AUTHOR]

Circadian rhythm affects drug-induced reward behaviour and the innate immune system. Peaks in reward-associated behaviour and immune responses typically occur during the active (dark) phase of rodents. While the role of the immune system, specifically, Toll-like receptor 4 (TLR4, an innate immune receptor) in drug-induced reward is becoming increasingly appreciated, it is unclear whether its effects vary according to light-cycle. Therefore, the aim of this study was to characterise the effects of the phase of the light-cycle and the state of the innate immune system on alcohol reward behaviour and subsequently determine whether the efficacy of targeting the immune component of drug reward depends upon the light-cycle. This study demonstrates that mice exhibit greater alcohol-induced conditioned place preference and alcohol two-bottle choice preference during the dark cycle. This effect overlapped with elevations in reward-, thirst- and immune-related genes. Administration of (+)-Naltrexone, a TLR4 antagonist, reduced immune-related gene mRNA expression and alcohol preference with its effects most pronounced during the dark cycle. However, (+)-Naltrexone, like other TLR4 antagonists exhibited off-target side effects, with a significant reduction in overall saccharin intake – an effect likely attributable to a reduction in tyrosine hydroxylase ( Th ) mRNA expression levels. Collectively, the study highlights a link between a time-of-day dependent influence of TLR4 on natural and alcohol reward-like behaviour in mice. [ABSTRACT FROM AUTHOR]

Sudden gains (SGs) are defined as abrupt and significant improvements in mental health symptoms that occur between two psychotherapy sessions. Preliminary evidence suggests that SGs may be an important pattern of symptom reduction in the treatment of alcohol use disorder (AUD) (i.e., a steep between-session reduction in drinking or alcohol craving frequency or intensity) (Drapkin, Epstein, McCrady, & Eddie, 2015). The current study examined SGs within two randomized clinical trials (RCTs) testing female-specific cognitive behavior therapy (CBT) protocol for AUD (n=146). We tested a priori hypotheses about whether women's baseline depression, anxiety, and confidence to be abstinent while in a negative emotional state would predict attainment of SGs after attending sessions that addressed depression, anxiety, and emotion regulation (i.e., sessions five and six of the 12-session protocol). Data were collected at baseline, within treatment, and 15months after baseline. Results showed that women with high levels of depression and/or anxiety and low confidence to be abstinent in a negative emotional state at baseline were more likely to experience a SG (steep decrease in drinking) after sessions five and six (p=0.02). Further, among women with high levels of depression and/or anxiety at baseline, those who experienced both a SG in drinking after session five/six and had higher confidence to remain abstinent in a negative emotional state at the end of treatment reported lower drinking frequency at 9- but not 15-month follow-up [95% CI=(-2.65, -0.86)]. Findings support the value of providing interventions targeting mood and emotion regulation in AUD treatment for women. [ABSTRACT FROM AUTHOR]

Two studies showed an improvement in clinical outcomes after alcohol approach bias retraining, a form of Cognitive Bias Modification (CBM). We investigated whether transcranial direct current stimulation (tDCS) could enhance effects of CBM. TDCS is a neuromodulation technique that can increase neuroplasticity and has previously been found to reduce craving. One hundred alcohol-dependent inpatients (91 used for analysis) were randomized into three experimental groups in a double-blind parallel design. The experimental group received four sessions of CBM while receiving 2 mA of anodal tDCS over the dorsolateral prefrontal cortex (DLPFC). There were two control groups: One received sham stimulation during training and one received active stimulation at a different moment. Treatment outcomes were abstinence duration (primary) and relapse after 3 and 12 months, craving and approach bias (secondary). Craving and approach bias scores decreased over time; there were no significant interactions with experimental condition. There was no effect on abstinence duration after three months (χ2(2) = 3.53, p = 0.77). However, a logistic regression on relapse rates after one year (standard outcome in the clinic, but not-preregistered) showed a trend when relevant predictors were included; relapse was lower in the condition receiving active stimulation during CBM only when comparing to sham stimulation (B = 1.52, S.E. = .836, p = .07, without predictors: p = .19). No strong evidence for a specific enhancement effect of tDCS on CBM was found. However, in a post-hoc analysis, tDCS combined with CBM showed a promising trend on treatment outcome. Important limitations are discussed, and replication is necessary to find more reliable effects. [ABSTRACT FROM AUTHOR]

Opioid antagonists such as naltrexone and nalmefene are used in drug therapy for alcoholism. Nalmefene, approved in Europe in February 2013 for the reduction of alcohol consumption, is used in patients with alcohol dependence. We report 11 cases of opioid withdrawal syndrome after a single dose of nalmefene in patients usually treated with methadone, buprenorphine, but also with fentanyl or loperamide. Nalmefene is both a partial agonist and an antagonist of opioid receptors. Regarding to its opioid antagonist activity, nalmefene is contraindicated in patients with an opioid treatment. Therefore, when prescribing or delivering nalmefene, healthcare professionals need to be vigilant about any type of opioid exposure, even masked or hidden, to avoid these potential life-threatening syndromes. [ABSTRACT FROM AUTHOR]

Background and aims There is inconsistent evidence that alcohol-specific coping is a mechanism of change in cognitive-behavioral therapy (CBT) for alcohol use disorder (AUD). Our primary aim was to test whether baseline dependence severity moderates the mediational effect of CBT on drinking outcomes via coping. Design Secondary data analysis of Project MATCH , a multi-site alcohol treatment trial in which participants, recruited in out-patient and aftercare arms, were randomized to three treatments: CBT, motivational enhancement therapy (MET) and Twelve-Step facilitation (TSF). Setting Nine research sites in the United States. Participants A total of 1063 adults with AUD. Measurements The primary outcomes were percentage days abstinent and percentage heavy drinking days at the 1-year follow-up. Coping was assessed with the Processes of Change Questionnaire . Dependence severity was measured with the Alcohol Dependence Scale . Findings Among the full available sample (across treatment arms), there were no significant moderated mediation effects. Double moderated mediation analyses indicated that several moderated mediation effects were moderated by treatment arm (all P < 0.05). In the out-patient arm, there were several significant moderated mediation effects (all P < 0.05), but no significant moderated mediation effects in the aftercare arm. For out-patient clients with high baseline dependence severity, end-of-treatment coping mediated the positive treatment effects of CBT, compared with both MET and TSF, on 1-year drinking outcomes (all P < 0.05). Coping did not mediate treatment effects of CBT among those with low or moderate dependence severity. Conclusions In the Project MATCH out-patient sample, whether or not coping mediated the effects of cognitive-behavioral therapy for alcohol use disorder was conditional on dependence severity. End-of-treatment coping mediated the positive treatment effects of cognitive-behavioral therapy on 1-year drinking outcomes among out-patient clients when dependence severity was high, but not when dependence severity was low or moderate. [ABSTRACT FROM AUTHOR]

Purpose: Women in alcohol treatment are more likely to relapse when in unpleasant, negative emotional states. Given the demonstrated benefits of exercise for decreasing depression, negative affect, and urges to drink, helping women engage in a lifestyle physical activity (LPA) intervention in early recovery may provide them a tool they can utilize "in the moment" in order to cope with negative emotional states and alcohol craving when relapse risk is highest. New digital fitness technologies (e.g., Fitbit activity monitor with web and mobile applications) may facilitate increases in physical activity (PA) through goal setting and self-monitoring.Method: We piloted a 12-week LPA+Fitbit intervention focused on strategically using bouts of PA to cope with affect and alcohol cravings to prevent relapse in 20 depressed women (mean age=39.5years) in alcohol treatment.Results: Participants wore their Fitbit on 73% of days during the intervention period. An average of 9174 steps/day were taken on the days the Fitbit was worn. Participants completed 4.7 of the 6 scheduled phone PA counseling sessions (78%). Among women who completed the intervention (n=15), 44% remained abstinent throughout the entire course of treatment. On average, women were abstinent on 95% of days during the 12-week intervention. Participants reported an increase in using PA to cope with either negative affect or urges to drink from baseline to end of treatment (p<0.05). Further, participants reported high satisfaction with the LPA+Fitbit intervention and with the Fitbit tracker.Conclusions: Further research is needed to evaluate the LPA+Fitbit intervention in a more rigorous randomized controlled trial. If the LPA+Fitbit intervention proves to be helpful during early recovery, this simple, low-cost and easily transported intervention can provide a much-needed alternate coping strategy to help reduce relapse risk among women in alcohol treatment. [ABSTRACT FROM AUTHOR]

Rationale: Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. Objectives: The present study tried to determine the effects of roflumilast on ethanol intake and preference. Methods: We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Results: Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. Conclusions: These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism. [ABSTRACT FROM AUTHOR]

Background: Many young people are reluctant to seek professional help for mental health problems, preferring to rely on their friends for support. It is therefore important to ensure that adolescents can identify signs of psychological distress in their peers, talk to them about these, and help them access appropriate services when necessary. The current study examined adolescents' ability to recognise symptoms of depression and alcohol misuse, perceived barriers to help-seeking, and their intentions to encourage a peer to seek help from a range of informal and formal help sources.Method: The current study used baseline data from a randomised controlled trial of a school-based intervention that teaches adolescents how to overcome barriers to accessing professional help for mental health and substance use problems (MAKINGtheLINK). Participants (n = 2456) were presented with two vignettes portraying depression and alcohol misuse, respectively, and were asked to identify the problems described. Participants provided data on their past help-seeking behaviour, confidence to help a peer, perceived barriers to help-seeking, and intentions to encourage a peer to seek help.Results: Health professionals were the main source of help that participants had relied on for depressive symptoms, followed by friends and parents. In contrast, friends were the main source of help that participants had relied on for alcohol and other drug problems, followed by health professionals and parents. Just over half of the sample correctly identified the problems described in the two vignettes, although the majority of participants were confident that they could talk to a peer and help them seek professional help if needed. Most agreed that the vignettes described problems that warranted professional help, however approximately half the sample was unsure or considered it unlikely that they would seek help if they experienced similar problems. For both disorders, participants were most likely to encourage a peer to seek help from their family, followed by formal help sources and friends.Conclusions: While the results point towards a greater willingness to approach formal help sources, particularly for depression, peers remain an important source of support for young people experiencing mental health and substance use problems. [ABSTRACT FROM AUTHOR]

Background: Concurrent epidemics of HIV, depression, alcohol abuse, and partner violence threaten maternal and child health (MCH) in South Africa. Although home visiting has been repeatedly demonstrated efficacious in research evaluations, efficacy disappears when programs are scaled broadly. In this cluster randomized controlled trial (RCT), we examine whether the benefits of ongoing accountability and supervision within an existing government funded and implemented community health workers (CHW) home visiting program ensure the effectiveness of home visiting.Methods/design: In the deeply rural, Eastern Cape of South Africa, CHW will be hired by the government and will be initially trained by the Philani Programme to conduct home visits with all pregnant mothers and their children until the children are 2 years old. Eight clinics will be randomized to receive either (1) the Accountable Care Condition in which additional monitoring and accountability systems that Philani routinely uses are implemented (4 clinics, 16 CHW, 450 households); or (2) a Standard Care Condition of initial Philani training, but with supervision and monitoring being delivered by local government structures and systems (4 clinics, 21 CHW, 450 households). In the Accountable Care Condition areas, the CHW's mobile phone reports, which are time-location stamped, will be monitored and data-informed supervision will be provided, as well as monitoring growth, medical adherence, mental health, and alcohol use outcomes. Interviewers will independently assess outcomes at pregnancy at 3, 6, 15, and 24 months post-birth. The primary outcome will be a composite score of documenting maternal HIV/TB testing, linkage to care, treatment adherence and retention, as well as child physical growth, cognitive functioning, and child behavior and developmental milestones.Discussion: The proposed cluster RCT will evaluate whether routinely implementing supervision and accountability procedures and monitoring CHWs' over time will improve MCH outcomes over the first 2 years of life.Trial Registration: ClinicalTrials.gov registration #NCT02957799 , registered on October 26, 2016. [ABSTRACT FROM AUTHOR]

The American College of Surgeons requires Level I and II trauma centers to provide brief intervention services to traumatically injured patients who screen positive for alcohol. Despite evidence supporting substantial cost savings and reduced re-injury associated with these services, brief interventions may not be uniformly delivered owing to a variety of demographic, clinical and operational characteristics. To inform service adjustments that may improve the reach of such services, we compared trauma patients who did and did not receive brief alcohol intervention services during their hospitalizations. Electronic medical records of injured patients admitted to a Level I trauma center between September 27, 2013 and March 11, 2014 with a positive blood alcohol concentration (N=189) were coded for demographic and clinical variables. Records of those who did not receive a brief intervention during their admission were reviewed for possible reasons why interventions were not delivered. Of the total sample, 115 patients (60.8%) received brief interventions. Patients who did and did not receive brief interventions did not differ on age, sex, race, blood alcohol concentration at admission, or mechanism of injury, indicating that patient characteristics were unlikely to bias service delivery. Instead, common features of patients who were referred but did not receive SBIRT interventions included admissions lasting fewer than two working days (12.7%) and persistent cognitive impairment following injury (9.0%). These findings align with previous studies suggesting that service reach could be improved by promoting dedicated and flexible staffing and adapting services to allow for SBIRT delivery in follow-up care settings. [ABSTRACT FROM AUTHOR]

Typically, health policy, practice and research views alcohol and other drug (AOD) 'problems' as objective things waiting to be detected, diagnosed and treated. However, this approach to policy development and treatment downplays the role of clinical practices, tools, discourses, and systems in shaping how AOD use is constituted as a 'problem'. For instance, people might present to AOD treatment with multiple psycho-social concerns, but usually only a singular AOD-associated 'problem' is considered serviceable. As the assumed nature of 'the serviceable problem' influences what treatment responses people receive, and how they may come to be enacted as 'addicted' or 'normal' subjects, it is important to subject clinical practices of problem formulation to critical analysis. Given that the reach of AOD treatment has expanded via the online medium, in this article we examine how 'problems' are produced in online alcohol counselling encounters involving people aged 55 and over. Drawing on poststructural approaches to problematisation, we not only trace how and what 'problems' are produced, but also what effects these give rise to. We discuss three approaches to problem formulation: (1) Addiction discourses at work; (2) Moving between concerns and alcohol 'problems'; (3) Making 'problems' complex and multiple. On the basis of this analysis, we argue that online AOD counselling does not just respond to pre-existing 'AOD problems'. Rather, through the social and clinical practices of formulation at work in clinical encounters, online counselling also produces them. Thus, given a different set of circumstances, practices and relations, 'problems' might be defined or emerge differently-perhaps not as 'problems' at all or perhaps as different kinds of concerns. We conclude by highlighting the need for a critical reflexivity in AOD treatment and policy in order to open up possibilities for different ways of engaging with, and responding to, people's needs in their complexity. [ABSTRACT FROM AUTHOR]

Background: Preclinical and clinical research suggest that the α1 receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to α1 blockers in alcohol-dependent (AD) patients is unknown. We previously reported a randomized controlled trial (RCT) where doxazosin, an α1 receptor antagonist with a more favorable pharmacokinetic profile than prazosin, reduced drinks per week (DPW) and heavy drinking days (HDD) in AD patients with a high family history density of alcoholism. In this study, we tested pre-treatment BP as another potentially valuable clinical moderator of doxazosin's response on alcohol consumption.Methods: This was a double-blind placebo-controlled RCT testing doxazosin up to 16mg/day in AD treatment-seeking patients (N=41). The hypothesized moderator effect of baseline standing systolic and diastolic BP on DPW and HDD was tested.Results: With pre-treatment standing diastolic BP as a moderator, there were significant BP x medication interactions for both DPW [**p=0.009, d=0.80] and HDD [*p=0.018, d=1.11]. Post-hoc analyses indicated significant doxazosin effects in patients with higher standing BP in reducing both DPW and HDD.Conclusion: These findings suggest that higher standing diastolic BP at baseline (pre-treatment) may represent a predictor of doxazosin's response on alcohol consumption in AD patients. These results further elucidate the possible efficacy and mechanisms of action of α1 receptor antagonism in AD individuals. [ABSTRACT FROM AUTHOR]

Background: Delirium tremens (DT) is a medical emergency. Many cases are treated and discharged from emergency services (ES), after complete or partial resolution of delirium. Few receive comprehensive inpatient addiction treatment (CIAT) after the initial emergency management. Objective: The objective of this study was to compare 6-month outcomes of treatment in alcohol-dependence syndrome (ADS) patients presenting with DT receiving either only emergency care or emergency care along with CIAT. Materials and Methods: In this prospective observational study, all patients of ADS presenting in DT over a 1-year period were followed up for 6 months. Patients who received care only in the emergency services (ES) (111) were compared with patients who received ES followed by CIAT (90). Primary followup measure was regular followup (RFU) at outpatient department, and patients not presenting for RFU received telephonic followup (TFU). Alcohol use status was monitored at 6 months, as per Feuerlein and Küfner criteria. Results: Patients who received both ES and CIAT had better RFU compared to patients treated in the ES alone at 6 months (71/90 vs. 17/111, respectively, P < 0.005). CIAT also resulted in better combined follow-up (RFU and TFU) (85/90 vs. 60/111, respectively, P < 0.005). Compared to ES treatment group alone, ES plus CIAT group had fewer relapses (41/85 vs. 42/60, respectively, P < 0.05). The most common reason for direct discharge from ES was nonavailability of beds for inpatient treatment. Conclusions: Merely emergency treatment of ADS patients presenting with DT does not provide satisfactory treatment outcome with respect to alcohol use. ES treatment followed by CIAT ensures better outcome in the form of fewer relapses and better follow up. [ABSTRACT FROM AUTHOR]

Aims The influence of tobacco use in alcohol-dependent individuals is not well understood, especially the role of snuffing, which is common in Northern Europe. The aim was therefore to investigate the influence of smoking and snuffing on the progression, severity and treatment outcome in alcohol-dependent individuals. The hypotheses were that concomitant tobacco use (i.e. smoking or snuffing) would enhance the progression and severity of alcohol dependence and be less beneficial for treatment outcome, relative to tobacco non-users. Methods Alcohol-dependent individuals (n = 347) were recruited from three treatment units specialized in alcohol use disorders. Participants were interviewed about their current and past alcohol and tobacco use at treatment entry and at a follow-up interview 2.5 years thereafter. Results The tobacco users (smokers and snuffers) had an earlier alcohol debut compared to the tobacco never-users. Snuffers reported regular alcohol consumption and inebriation at an earlier age in contrast to smokers and tobacco never-users. There were no difference between the groups regarding treatment outcome. Conclusions This study highlights the importance of studying not only the influence of smoking but also of snuffing on the progression, severity and treatment outcome in individuals with alcohol dependence. [ABSTRACT FROM AUTHOR]

We report on the treatment and successful outcome of a 58-year-old Native American male with a history of complex trauma presenting with dissociative identity disorder (DID) and major depressive disorder. The treatment included a trauma-informed phase-based psychotherapy as recommended by the International Society for the Study of Trauma and Dissociation for treating DID. We assessed symptoms at baseline and at three additional time points over the course of 14 months. We utilized the Reliable Change Index to examine statistically significant change in symptoms over the course of treatment. Significant symptom improvements were realized posttreatment across all measured domains of functioning, including dissociative symptoms, alcohol abuse, depression, anxiety, and emotion regulation skills. Moreover, the client no longer met criteria for DID, major depressive disorder, or alcohol abuse. Results are discussed in terms of the effectiveness of trauma-focused, phase-based treatment for DID for cases of complex trauma with comorbid disorders. [ABSTRACT FROM PUBLISHER]

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established. [ABSTRACT FROM AUTHOR]

Aims We tested the efficacy of daily contingent reinforcement for reducing alcohol use compared with (yoked) non-contingent reinforcement (NR) using a transdermal alcohol sensor to detect alcohol use. Design Pilot randomized controlled design with 1 baseline week, 3 intervention weeks and 1-month follow-up. Setting New England, USA. Participants Heavy drinking adults (46.7% female) not seeking treatment were randomized to (1) an escalating schedule of cash reinforcement (CR; n = 15) for days on which alcohol was neither reported nor detected or (2) yoked NR ( n = 15). Intervention and comparator Reinforcement for CR participants started at $5 and increased $2 every subsequent day on which alcohol was not detected or reported, to a maximum of $17. Participants received no reinforcement for days on which alcohol use was detected or reported, and the reinforcer value was re-set to $5 the day after a drinking day. NR participants were yoked to the daily reinforcer value of an individual in the CR condition, in order of enrollment. Paired participants in CR and NR therefore received the same amount of money, but the amount for the NR participant was not behavior-related. Measurements The primary outcome was percentage of days without sensor-detected drinking. Secondary outcomes were number of consecutive days with no detected drinking, peak transdermal alcohol concentration (TAC), self-reported drinks per week and drinking below NIH low-risk guidelines. Findings Controlling for baseline, CR had a higher percentage of days with no drinking detected (54.3%) than NR (31.2%) during intervention weeks [ P = 0.05, Cohen's d = 0.74; 95% confidence interval (CI) = 0.007-1.47]. The longest period of consecutive days with no drinking detected was 8.0 for CR versus 2.9 for NR ( P = 0.03, d = 0.85; 95% CI = 0.08-1.61). Peak TAC during intervention showed a non-significant group difference ( P = 0.20; d = 0.48; 95% CI = 0.00-1.18); a similar result was found for drinks per week ( P = 0.12; d = 0.59; 95% CI = 0.00-1.30). Four times more participants in CR drank below NIH low-risk drinking guidelines during intervention than did participants in NR: 31.1 versus 7.1% ( P = 0.07; d = 0.71; 95% CI = -0.04 to 1.46). At 1-month follow-up, the highest number of consecutive days without drinking (self-report) did not differ significantly between conditions ( P = 0.26), but showed a medium effect size ( d = 0.44; 95% CI = −0.32 to 1.18). Conclusions Cash incentives linked to a transdermal alcohol sensor can reduce heavy alcohol consumption while the incentives are in operation. [ABSTRACT FROM AUTHOR]

Background: The automatic tendency to attend to and focus on substance-related cues in the environment (attentional bias), has been found to contribute to the persistence of addiction. Attentional bias modification (ABM) interventions might, therefore, contribute to treatment outcome and the reduction of relapse rates. Based on some promising research findings, we designed a study to test the clinical relevance of ABM as an add-on component of regular intervention for alcohol and cannabis patients. Design/Methods: The current protocol describes a study which will investigate the effectiveness and costeffectiveness of a newly developed home-delivered, multi-session, internet-based ABM (iABM) intervention as an add-on to treatment as usual (TAU). TAU consists of cognitive behavioural therapy-based treatment according to the Dutch guidelines for the treatment of addiction. Participants (N = 213) will be outpatients from specialized addiction care institutions diagnosed with alcohol or cannabis dependency who will be randomly assigned to one of three conditions: TAU + iABM; TAU + placebo condition; TAU-only. Primary outcome measures are substance use, craving, and rates of relapse. Changes in attentional bias will be measured to investigate whether changes in primary outcome measures can be attributed to the modification of attentional bias. Indices of cost-effectiveness and secondary physical and psychological complaints (depression, anxiety, and stress) are assessed as secondary outcome measures. Discussion: This randomized control trial will be the first to investigate whether a home-delivered, multi-session iABM intervention is (cost-) effective in reducing relapse rates in alcohol and cannabis dependency as an add-on to TAU, compared with an active and a waiting list control group. If proven effective, this ABM intervention could be easily implemented as a home-delivered component of current TAU. [ABSTRACT FROM AUTHOR]

Background and Aims The clinical sequelae and comorbidities of alcoholic liver disease (ALD) often require hospitalization. The aims of this study were to (1) compare the average costs of hospitalizations with ALD and the costs of hospitalizations with other alcohol-related diagnoses that do not involve the liver; and (2) estimate the percentage of the difference in costs between the ALD and non-ALD hospitalizations that may be attributed to ascites, protein-calorie malnutrition and other conditions. Design The 2012 National Inpatient Sample is a population-based cross-sectional database representing more than 94% of all discharges from community hospitals in the United States. Setting Community hospitals in the United States. Participants The sample included 72 531 hospitalizations with ALD and 287 047 hospitalizations with other alcohol-related diagnoses. Measurements The dependent variable was total in-patient costs. We estimated the contribution of ascites, protein-calorie malnutrition and other conditions to the difference in costs between patients with ALD and patients with other diagnoses. Findings Average costs for ALD patients were $3188.4 higher than those for patients with other diagnoses ($13 543 versus $10 355; P < 0.001). Among all conditions in the analysis, protein-calorie malnutrition had the largest impact on costs [$6501; 95% confidence interval (CI) = 5956, 7045; P < 0.001] accounting for 12% of the higher costs of ALD stays. Conclusions Costs of hospital care for patients with alcoholic liver disease are higher than those for patients with other alcohol-related diagnoses. These increased costs are associated with specific clinical sequelae and comorbidities, with protein-calorie malnutrition-a largely preventable condition-making a substantial contribution. [ABSTRACT FROM AUTHOR]

Background: Alcohol use has important adverse effects on people living with HIV (PLWH). This study of patients with recognized unhealthy alcohol use estimated and compared rates of alcohol-related care received by PLWH and HIV- patients.Methods: Outpatients from the Veterans Health Administration who had one or more positive screen(s) for unhealthy alcohol use (AUDIT-C≥5) documented in their medical records 10/2009-5/2013 were eligible. Primary and secondary outcomes were brief intervention documented ≤14days after a positive alcohol screen, and a composite measure of any alcohol-related care (brief intervention, specialty addictions treatment or pharmacotherapy documented ≤365 days), respectively. Unadjusted and adjusted regression analyses compared alcohol-related care outcomes in PLWH and HIV- patients.Results: The sample included 830,825 outpatients (3,514 PLWH), reflecting 1,172,606 positive screens (1-5 per patient). For PLWH, 57.0% (95% confidence interval 55.4-58.5%) of positive screens were followed by brief intervention, compared to 73.8% (73.7-73.9%) for HIV- patients [relative rate: 0.77 (0.75-0.79), p<0.001]. After adjustment, comparable proportions were 61.0% (59.3-62.6%) for PLWH and 73.7% (73.6-73.8%) for HIV- patients [adjusted RR=0.83 (0.80-0.85); p<0.001]. Secondary outcome results were similar: for PLWH and HIV- patients, 67.1% (65.7-68.6%) and 77.7% (95% CI 77.7-77.8%) of positive screens, respectively, were followed by any alcohol-related care after adjustment [adjusted RR=0.86 (0.85-0.88), p<0.001].Conclusions: In this large national sample of VA outpatients with unhealthy alcohol use, PLWH were less likely to receive alcohol-related care than HIV- patients. Special efforts may be needed to ensure alcohol-related care reaches PLWH. [ABSTRACT FROM AUTHOR]

Background: Among HIV+ patients, alcohol use is a highly prevalent risk factor for both HIV transmission and poor adherence to HIV treatment. The large-scale implementation of effective interventions for treating alcohol problems remains a challenge in low-income countries with generalized HIV epidemics. It is essential to consider an intervention's cost-effectiveness in dollars-per-health-outcome, and the long-term economic impact -or "return on investment" in monetary terms.Methods: We conducted a cost-benefit analysis, measuring economic return on investment, of a task-shifted cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use in a modeled cohort of 13,440 outpatients in Kenya. In our base-case, we estimated the costs and economic benefits from a societal perspective across a six-year time horizon, with a 3% annual discount rate. Costs included all costs associated with training and administering task-shifted CBT therapy. Benefits included the economic impact of lowered HIV incidence as well as the improvements in household and labor-force productivity. We conducted univariate and multivariate probabilistic sensitivity analyses to test the robustness of our results.Results: Under the base case, total costs for CBT rollout was $554,000, the value of benefits were $628,000, and the benefit-to-cost ratio was 1.13. Sensitivity analyses showed that under most assumptions, the benefit-to-cost ratio remained above unity indicating that the intervention was cost-saving (i.e., had positive return on investment). The duration of the treatment effect most effected the results in sensitivity analyses.Conclusions: CBT can be effectively and economically task-shifted to paraprofessionals in Kenya. The intervention can generate not only reductions in morbidity and mortality, but also economic savings for the health system in the medium and long term. The findings have implications for other countries with generalized HIV epidemics, high prevalence of alcohol consumption, and shortages of mental health professionals.Trial Registration: This paper uses data derived from "Cognitive Behavioral Treatment to Reduce Alcohol Use Among HIV-Infected Kenyans (KHBS)" with ClinicalTrials.gov registration NCT00792519 on 11/17/2008; and preliminary data from "A Stage 2 Cognitive-behavioral Trial: Reduce Alcohol First in Kenya Intervention" ( NCT01503255 , registered on 12/16/2011). [ABSTRACT FROM AUTHOR]

Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol. Hence, in the last years, several pre-clinical studies have been performed in order to analyze the effects of the sequestering ACD agents in the prevention of ethanol relapse-like drinking behavior as well as in chronic alcohol consumption. In this sense, one of the most explored interventions has been the administration of D-Penicillamine (DP). These pre-clinical studies, that we critically summarize in this article, are considered a critical step for the potential development of a novel pharmacotherapeutic strategy for alcohol addiction treatment that could improve the outcomes of current ones. Thus, on one hand, several experimental findings provide the rationale for using DP as a novel therapeutic intervention alone and/or in combination to prevent relapse into alcohol seeking and consumption. On the other hand, its effectiveness in reducing voluntary ethanol consumption in long-term experienced animals still remains unclear. Finally, this drug offers the additional advantage that has already been approved for use in humans, hence it could be easily implemented as a new therapeutic intervention for relapse prevention in alcoholism. [ABSTRACT FROM AUTHOR]